The Latest Research
Latest Research Highlights from the NNPDF Research
Contact the NNPDF Research Committee through the NNPDF Central Office.
Orphazyme Announces Proposed Clinical Trial
Dear NPD Community,
Orphazyme, a Danish biotech company, announced its intention to conduct a trial of rhHSP70 as a therapeutic intervention in NPC disease, at a scientific conference in Italy this week (15th-19th April 2013).
Orphazyme has provided information for patients and families which will be generally available through patient organizations across the world. This information has been issued on the understanding that much has still to be confirmed / agreed by the regulatory authorities, so please be aware that some of the details may change. View the Orphazyme Slide Presentation.
To assist you, we have produced an additional document that summarizes the main points: View the: Orphazyme Trial Announcement Summary .
In order to facilitate communication further, Orphazyme intends to launch a web page for the trial and to include a “Frequently Asked Questions” section on the page. As soon as this information is available, we will share it with you. Further information about Orphazyme can be found on their website: http://www.orphazyme.com/
[Apr 19th, 2013 blg]
NNPDF Fellowship Updates
~ Apr 18th, 2013 ~
Dear NPD Community,
The most recent lay summarys for our current fellowships can now be viewed on the Funded Fellowships page.
[Apr 18th, 2013 blg]
Michael, Marcia and Christa Parseghian Scientific Conference for Niemann-Pick Type C Research
~ Apr 4th, 2013 ~
Dear NPD Community,
The annual Michael, Marcia, and Christa Parseghian Scientific Conference for Niemann‐Pick Type C Research brings together researchers, supporters, families and children with NPC from around the world. Participants, representing 31 institutions and five foundations, include people from the United States, Canada, Brazil, Germany, the Netherlands, Switzerland, Australia and France.
This meeting includes the latest updates in research on Niemann-Pick type C from the experts that are conducting research.
For more information on dates, times and registration of all available conferences, Click Here.
[Apr 4th, 2013 blg]
Old Drug Offers New Hope Against Rare, Deadly Childhood Disease
~ Apr 4th, 2013 ~
Dear NPD Community,
An article was recently released about Dr. Ory, our NNPDF scientific advisor, and the National Institue of Health's research into Cyclodextrin and the NPC clinical trial.
“We’ve been studying this disease for many years, and we began looking at this drug in earnest about
five years ago,” Ory says. “In animal models of NPC, we see significant benefit in both neurological
function and survival. It’s superior to all other compounds we have tested in the animal models.”
The nine patients they are enrolling in this Phase 1 trial are being treated at the NIH Clinical Center
in Bethesda, MD. In St. Louis, Ory and his colleagues are tracking their progress with new techniques
developed at Washington University.
To view the full article, Click Here.
[Apr 4th, 2013 blg]
Peter G. Pentchev Fellowships Open for Applications
~ Mar 1st, 2013 ~
Dear NPD Community,
The National Niemann-Pick Disease Foundation (NNPDF) invites applications for postdoctoral research fellowships examining the biology of Niemann-Pick Type C (NPC) disease, a lethal neurodegenerative disease for which there are no effective therapies.
M.D., Ph. D. and D.V.M. postdoctoral fellows are eligible to apply for funding to improve our understanding of the biology and pathogenesis of NPC disease. Preference will be given to research projects developing new therapies for NPC and identifying biomarkers of disease activity for diagnosis and clinical trials.
Visit the Fellowships page for further information.
[Mar 1, 2013 blg]
Loire Valley Research Conference 2012 Highlights
~ Feb 19th, 2013 ~
Dear NPD Community,
The International Niemann-Pick Disease Alliance (INPDA) hosted the Loire Valley research conference in 2012.
The LVM is a unique international scientific meeting organized as part of the ongoing International Niemann-Pick Disease Association (INPDA) program of facilitating research into Niemann-Pick type C disease (NPC).
The meeting objectives were to bring together, in an open setting, a group of European scientists studying NPC or related diseases to:
- Facilitate free and open discussions on the current state of research into the disease and, advances in the associated cellular anatomy and biochemical physiology.
- Analyze research priorities and identify potential collaborations over the next 2 years.
To view the highlights from the conference, Click Here.
[Feb 19, 2013 blg]
NIH Announcement - Cyclodextrin Trial Update
~ January 31st, 2013 ~
Dear NPD Community,
The NNPDF central offices received the following update on the Cyclodextrin trial from the NIH Research Team.
"The NIH cyclodextrin trial has started and the first patient will receive the drug on Monday 2/4. We are very excited to get started and to get data that will direct future studies of cyclodextrin in NPC. We have been in contact with many families and would like to provide an update about the trial screening process.
The patients in this trial are grouped into "cohorts" of three patients each. Because we did not know exactly when we would be able to start the trial, the first three patients were selected because they live relatively close to the NIH or were able to come to the NIH with very little notice (less than 2 weeks in one case). Only the first 3 patients have been scheduled. We have not yet filled the remaining slots for the trial.
The FDA asked us to start at a lower dose than we initially proposed. The initial data from these first three patients will determine what exactly we will do next. We decided that we will need to re-screen patients when we are ready to schedule the next cohort (patients 4, 5 and 6), in order to make sure they are still eligible. This will also need to happen again with the last 3 patients. We have a screening log of all individuals who we have screened and will be in touch with families when we are prepared to schedule the remaining slots in the trial.
We would like to thank you for your continued patience and we apologize for any delays in returning phone calls or emails. We are doing our best to get this trial going as quickly and safely as possible so we can answer questions about cyclodextrin in NPC. Please do not hesitate to contact us with additional questions.
The NIH NPC Research Team"
[Jan 31, 2013 blg]
Dr. Charles Vite Cyclodextrin Therapy Report
Dear Friends and Families,
Dr. Charles Vite, from the School of Veterinary Medicine in Pennsylvania, has been kind enough to send along his report from the presentation he gave over the summer.
To view it: Click Here
[Jan 17, 2013 blg]
Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin
~ November 28th, 2012 ~
Cyclodextrin (HP-β-CD) for NPC1 Disease
~ Clinical Trial Strategy ~
UPDATE ~ November 28th, 2012 ~ UPDATE
Therapeutics for Rare and Neglected Diseases (TRND)
National Institutes of Health ~ Bethesda, MD
Dear National Niemann-Pick Disease Foundation Family Members,
The latest release pertaining to the upcoming NIH NPC clinical trial has been made available to the NNPDF. To view the NIH NPC Cyclodextrin Clinical Trial Flyer ~ dated: 11/28/12 ~ click here.
This study titled: 2-hydroxypropyl-B-cyclodextrin (HP-B-CD) in Niemann-Pick Disease, type C1, is in the process of being reviewed by the FDA and the team of researchers and physicians associated with the Therapeutics for Rare and Neglected Disease ~ Niemann-Pick Type C Disease Team (TRND NPC Team) at the NIH are hopeful that they will be able to begin enrolling patients in January of 2013.
The National Niemann-Pick Disease Foundation is pleased that we are able to forward this information along to our family membership. The NIH attached flyer specifies that interested parties should note your interest in possible trial participation by e-mailing a representative at the NIH: email@example.com
Please note: If you do NOT have access to the internet or an e-mail account please contact the NNPDF Central Offices at the 920-563-0930 and we will assist you in reaching the appropriate contact individual(s) at the NIH for more information.
This is indeed, a very exciting time for all of our NNPDF family community and, more importantly, all of our precious loved ones diagnosed with Niemann-Pick Disease Type C.
We WILL Persevere in our Quest for a Cure!
Kind Regards,Nadine M. Hill
Executive Director; National Niemann-Pick Disease Foundation
For a historical timeline on the Cyclodextrin (HP-β-CD) for NPC1 Disease Clinical Strategy ~ outlined by the NNPDF ~ please follow the link above.
[Nov 28, 2012 nmh]
National Niemann-Pick Disease Foundation Research Post-Doctoral Fellowship Funding Announcement
The National Niemann Pick Disease Foundation (NNPDF) has chosen to fund post doctoral fellowships for the past several years. These fellowships support a post doctoral fellow to work on a research project in the field of Niemann-Pick Disease for a period of two years. The NNPDF has utilized strategies to allocate funds raised by NPD families by disease type to support these specific NPD disease focused fellowships.
In the past several years, NNPDF has been able to fund a number of fellowships for Niemann-Pick Disease Type C. These are called the Peter G. Pentchev Research Fellowships and the NNPDF in conjunction with the Canadian Chapter of the National Niemann-Pick Disease Foundation (CCNNPDF) are currently funding the work of five (5) Peter Pentchev fellowships.
This year we were able to establish a fellowship for Acid Sphingomyelinase Deficiency (ASMD; i.e., Types A and B Niemann-Pick Disease) research entitled the Edward H. Schuchman Research Fellowship for ASMD Niemann Pick Disease. We received 5 strong applications for the fellowship and I am pleased to announce that the first Edward H. Schuchman Fellowship has been awarded to Dr. Lluis Samaranch Gusi (sponsor Dr. Krystof S. Bankiewicz, MD, Ph.D.) at the University of California San Francisco.
This fellowship research project is entitled: “AAV9 mediated human acid sphingomyelinase expression in the non-human primate brain; Preclinical development of gene therapy for Niemann-Pick Disease Type A”. The goal of this project is to develop a treatment for the neurological consequences of Niemann-Pick Type A Disease. This project will evaluate the feasibility of delivering an adeno-associated virus encoding human acid sphingomyelinase globally into the brain by injection of a vector into the brain and/or the spinal canal.
Respectfully submitted by:
NNPDF Research Committee Co-chair
For more detailed information please Click here.
For information on the history of Research funding you can visit the following pages:
[Nov. 27, 2012 blg]
Update on Clinical Trial of Enzyme Replacement Therapy (ERT)
Dateline: November 15th, 2012 ~ The National Niemann-Pick Disease Foundation (NNPDF) has been staying in touch with representatives from Genzyme with regard to the completion of the Phase I and the status of Phase 2 of the Enzyme Replacement Therapy (ERT) clinical trial for Acid Sphingomyelinase Deficiency (ASMD) NPD Type B.
This program remains a key priority for Sanofi. They are committed to the Niemann-Pick community and have provided the NNPDF with the following update on the Genzyme-sponsored Acid Sphingomyelinase Deficiency (ASMD) Clinical Trials.
To that end, the Enxyme Replacement Therapy (ERT) team has made the following announcement available to the NNPDF Acid Sphingomyelinase Deficiency (ASMD) NPD Type B.
In addition, the NNPDF has created an historical time-line outlining strategic infomation given to the NNPDF during the development of the ERT clinical trial. Follow this link for more information.
If you have any questions regarding this update ~ please feel free to contact the NNPDF Central Office at: 1-877-287-3672. The NNPDF will continue to bring you more information as it becomes available.
[Nov. 21, 2012 nmh]
Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin
~ November 2012 ~
Planned Phase I Study of Cyclodextrin (HP-β-CD) for NPC1 Disease
Since our last communication in September 21, 2012, the National Institutes of Health Therapeutics for Rare and Neglected ~ Niemann-Pick Disease Type C team has continued to move forward in the preparation of the Phase I Study of Cyclodextrin (HP-b-CD) for NPC1 Disease.
The TRND NPC Team is pleased to announce that the Investigational New Drug (IND) application for intraventricular hydroxypropyl-β-cyclodextrin (HPBCD) was filed with the FDA today, November 14th, 2012. This was a major effort by multiple research laboratories, several NIH institutes, Johnson and Johnson and a team of pharmaceutical and regulatory consultants. This effort would not have been possible without the assistance of the many patient support organizations.
Our ultimate goal is to develop a safe, effective and accessible therapy for all individuals with NPC1. The IND filing is a major step in this process, but just one of the initial steps. We are hopeful that the very promising preclinical findings in mice and cats will translate to an effective therapy in individuals with NPC1. The goal of this first trial is to rapidly determine a safe and biochemically effective dose of HPBCD. These data are critical to the proper design and execution of a multicenter efficacy trial that will allow this drug, if determined to be safe and effective, to be approved by regulatory agencies, and ultimately to be made available to all NPC1 patients.
We appreciate the ongoing support from the NPC community and will continue to update the community on this trial.
For questions email us at firstname.lastname@example.org
Respectfully submitted by:
TRND NPC Team
Therapeutics for Rare and Neglected Disease ~ Niemann-Pick Type C Disease Team
For additioanl updates and background on the Cyclodextrin Trials at NIH follow the NNPDF Web site Cyclodextrin page.
[Nov 14, 2012 nmh]
FDA Safety and Innovation Act Signed: Monumental Step Toward Development of
Safe and Effective Treatments for Americans With Rare Diseases
The FDA Safety and Innovation Act (FDASIA), signed by President Obama July 9, contains the most groundbreaking measures for rare disease patients and their families since the Orphan Drug Act of 1983, according to the the National Organization for Rare Disorders (NORD).
"This legislation represents true progress for people with rare diseases, who often struggle to access treatments for their disorders," NORD President and CEO Peter L. Saltonstall said.
Specific to the rare disease community, the Act provides the following:
accelerated patient access to new medical treatments
the development of Humanitarian Use Devices (medical devices for small patient populations)
accelerated development of "breakthrough therapies" -- those that show early promise
enhanced FDA consultation with rare disease medical experts
a rare pediatric disease priority review voucher incentive program
resolution of conflict-of-interest issues that kept voices of rare disease medical experts from being heard
Read the full NORD press release here.
[July 12, 2012 mem]
FDA User Fee Bill Promises Real Hope for Rare Disease Patients
Recent House and Senate passage of The Food and Drug Administration Safety and Innovation Act (FDASIA), S. 3187, constitutes landmark legislation that will encourage the development of new treatments for the 30 million Americans suffering from rare diseases. There are currently fewer than 400 treatments approved by the U.S. Food and Drug Administration (FDA) for nearly 7000 rare diseases which have been identified.
According to a press release issued by the Kakkis Everylife Foundation on June 27:
FDASIA includes the reauthorization of the Prescription Drug User Fee Act (PDUFA), the culmination of more than a year of negotiations between industry and the FDA and advocacy by the patient community to ensure the reauthorization will encourage the development of new treatments. The legislation passed the House and Senate with broad bipartisan support and is expected to be signed by the President in the coming week.
Read the full press release here.
[June 28, 2012 mem]
Mount Sinai Study Looks at Skeletal Manifestations in NPB
The abstract of an article on a study titled Skeletal manifestations in pediatric and adult patients with Niemann Pick disease type B has been posted to PubMed. The study's authors include Dr. Melissa Wasserstein, a physician well-known to many NNPDF members, and others from the Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine, New York.
The article concludes: "Skeletal involvement is a common and previously unrecognized manifestation of NPD-B. The association between splenomegaly and BMD lends further support to spleen size as an indicator of disease severity."
Read the abstract here.
[June 25, 2012 mem]
Update on Clinical Trial of Enzyme Replacement Therapy (ERT)
The National Niemann-Pick Disease Foundation (NNPDF) has been staying in touch with representatives from Genzyme with regard to the status of Phase 2 of the Enzyme Replacement Therapy (ERT) clinical trial for Acid Sphingomyelinase Deficiency (ASMD) NPD Type B. It seems there has been some confusion among members of the ASMD community; please note that we have contacted Genzyme and confirmed that the Phase 2 trial has not been cancelled and the Genzyme/Sanofi Company is committed to the ongoing support of our NPD Type A and B patients and families.
Genzyme has advised that they are still actively preparing for a Phase 2 clinical trial for enzyme replacement therapy in ASMD/NPD Type B. The trial is expected to evaluate the safety and efficacy of different doses of rhASM when administered once every two weeks.
The program remains a key priority for Sanofi. They are committed to the Niemann-Pick community and have provided the NNPDF with the following update on the Genzyme-sponsored Acid Sphingomyelinase Deficiency (ASMD) Clinical Trials.
If you have any questions regarding this update ~ please feel free to contact the NNPDF Central Office at: 1-877-287-3672. The NNPDF will continue to bring you more information as it becomes available.
Update from Genzyme on Acid Sphingomyelinase Deficiency (ASMD) Clinical Trials
Genzyme, a Sanofi company, is continuing efforts to develop recombinant human acid sphingomyelinase (rhASM) for the potential treatment of the non-neurological manifestations of acid sphingomyelinase deficiency (ASMD, also known as Niemann-Pick disease Types A and B).
We are actively preparing for a Phase 2 clinical trial of rhASM in Niemann-Pick B patients to evaluate the safety and efficacy of different doses of rhASM when administered once every two weeks. In preparation for the trial, we have sought feedback from the FDA, are evaluating potential study centers worldwide, and are assessing our short- and long-term manufacturing plans.
We are also beginning to schedule the long-term follow-up visits for the natural history study of Niemann-Pick B patients that began in 2001 in the US, France, Italy, Germany, and Brazil. These vists are expected to yield important information about disease progression in the absence of treatment and may be included in a potential drug application filing in the future.
Our entire organization, from the Genzyme rare disease team to our colleagues at Sanofi, is committed to the development of rhASM and to addressing the unmet medical need of patients with ASMD.
We appreciate the support of the global Niemann-Pick disease community and will provide another update as soon as we are able to confirm a start date for the Phase 2 clinical trial.
500 Kendall Street
Cambridge, MA 02142
[Apr 26, 2012 mem]
Blood Draws to Support NPC Research
Two blood draws coordinated by NNPDF family volunteers will support research into a blood test to diagnose Niemann-Pick Disease Type C (NPC). The diagnostic blood test is expected to provide a faster, easier and more comfortable method than the current skin punch biopsy diagnostic test.
Karen Quandt, mother of 15-year-old Ty Quandt (NPC), organized a blood draw earlier this month to collect samples from healthy (non-NPD) teens to serve as pediatric control samples (see photos above). Rebecca Spencer, mother of 6-year-old Johnathan Spencer (NPC), is organizing a blood draw for April, in which samples from younger non-NPD children will be drawn for the same purpose.
The research is being done at the National Institutes of Health (NIH) in Bethesda, Maryland, and at Washington University School of Medicine in St. Louis, Missouri.
Thank you to Karen, Rebecca, the volunteers, and especially the donors, for participating in this important project!
[Mar 20, 2012 mem]
Request for Applications for Edward H. Schuchman Research Fellowship
The National Niemann-Pick Disease Foundation invites applications for postdoctoral research fellowships examining the biology of Acid Sphingomyelinase Deficiency (ASMD; i.e., Types A and B Niemann-Pick Disease), a lysosomal storage disease of varying symptoms, onset and complexity.
M.D., Ph.D., and/or D.V.M. postdoctoral fellows are eligible to apply for funding to improve our understanding of the biology and pathogenesis of Acid Sphingomyelinase Deficiency (ASMD; i.e., Types A and B Niemann-Pick Disease). Preference will be given to research projects developing new therapies for ASMD, and for identifying biomarkers to improve diagnosis or to monitor disease progression and efficacy in clinical trials.
The fellowship provides support of $40,000 per annum for two years and may be renewable based on performance. Applicants must be currently associated with a recognized laboratory.
These fellowships are named for Edward H. Schuchman, Ph.D. a pioneer in ASMD research and supporter of those affected by Niemann-Pick Disease.
Applications are due May 1, 2012, and should be submitted by email to the Research Committee Chair. Applicants will be informed of the funding decision by August 15, 2012, via email. Fellowships awarded will begin September 1, 2012.
[Mar 9, 2012 mem]
EMBO Molecular Medicine Workshop
Molecular Medicine of Sphingolipids
Ramot Resort Hotel, Sea of Galilee, Israel
October 16 - 21, 2012
"The aim of this EMBO Molecular Medicine Workshop on sphingolipids is to serve as a forum where basic researchers in collaboration with the pharmaceutical industry define the next stage of pre-clinical and clinical development of this fascinating class of lipids named for the secrets of the Sphinx."
See http://events.embo.org/12-sphingolipids/index.html for more information.
[Apr 23, 2012]
Parseghian Conference for NPC Research
University of Notre Dame
June 7 - 9, 2012
The Michael, Marcia and Christa Parseghian Scientific Conference for Niemann-Pick Type C Research will be held at the University of Notre Dame in South Bend, Indiana, on June 7th-9th, 2012.
[Mar 1, 2012 mem]
Request for Applications for Peter G. Pentchev Research Fellowship
Funding Research into Niemann-Pick Disease Type C
Deadline for Applications -- May 1, 2012
The National Niemann-Pick Disease Foundation is pleased to announce a request for applications for the 2012 Peter G. Pentchev Research Fellowship, examining the biology of Niemann-Pick Disease Type C.
M.D., Ph.D. and D.V.M. postdoctoral researchers are eligible to apply for funding to improve our understanding of the biology and pathogenesis of NPC disease. Preference will be given to research projects developing new therapies for NPC, and identifying biomarkers of disease activity for diagnosis and clinical trials.
The Pentchev Fellowships provide support of $50,000 per year for two years and may be renewable based on performance. Applications are due May 1, 2012, and fellowships awarded will begin September 1, 2012.
Visit http://www.nnpdf.org/npresearch_01.html and http://www.nnpdf.org/PeterPentchevResearchFellowship.html for more information about the NNPDF ’s program of research and the application process for the Pentchev Fellowship. Read about current and past NNPDF-funded research projects at: http://www.nnpdf.org/FellowshipsFunded.html.
[Feb 29, 2012 mem]
NIH Clinical Research Trials and You
The NIH recently announced the launch of a new Web site titled NIH Clinical Research Trials and You, geared for those considering participating in a clinical trial.
According to the press release announcing the new site, "Clinical trials are essential for identifying and understanding ways to prevent, diagnose, and treat disease. Research has shown that among the greatest challenges to recruitment of volunteers is the lack of general knowledge about what trials involve, where they are carried out, and who may participate."
This new Web site aims to help potential participants learn about clinical trials and make an informed decision about whether they should take part. The site includes sections on "The Basics," "Volunteer Stories," "Researcher Stories," "Finding a Trial." Also, "For Health Care Providers," "Educational Resources," a glossary of terms, and much more.
Visit the new site at http://www.nih.gov/health/clinicaltrials/ to learn more.
[Feb 14, 2012 mem]
Latest Update on Planning for NIH's Clinical Trial of Cyclodextrin
The NIH/TRND NPC team met again with representatives of the FDA on Tuesday, December 13, to discuss plans for the upcoming clinical trial of cyclodextrin, and we are pleased to be able to share the update below.
NNPDF members can be assured the foundation will continue to keep families up-to-date on information about plans for this and all clinical trials as details become available. Updates will be posted here to the NewsLine page, as well as to the Facebook page and the listserv groups.
For more information about TRND (Therapies for Rare and Neglected Diseases program) and the six pilot projects selected (including NPC), see this press release from NIH.
Update from the December 13 meeting:
Dear families and friends of the NPC community,
The collaborative group planning a cyclodextrin clinical trial at the National Institutes of Health (NIH) for the treatment of Niemann-Pick type C (NPC) disease met with the Food and Drug Administration (FDA) on Tuesday, December 13, 2011 as a follow up to the recently held November pre-IND meeting. On November 1, we met with the FDA Review Division staff to discuss the proposed development plan for cyclodextrin and needs for the IND application package.
Representatives from the Therapeutics for Rare and Neglected Diseases (TRND) group at the NIH, as well as several NPC researchers, Johnson & Johnson, and consultants from RRD International, LLC, participated in this meeting.
While the November meeting focused on the drug safety and toxicology data, the purpose of the December meeting was to discuss the proposed clinical trial design. Overall, the feedback from FDA was very positive and their comments and guidance will assist us in the generation of an IND application that is agreeable to FDA, thus allowing us to move forward with the initial clinical trial as soon as possible.
Preclinical toxicology and safety studies in animals are ongoing, and additional studies will be initiated shortly. These required nonclinical studies will guide the selection of drug doses for the initial trial and will provide essential safety information. In the upcoming months, we will be evaluating these study results and will incorporate them into the IND application and initial clinical protocol, which will then be submitted to FDA and the NIH Institutional Review Board (IRB). Once we have agreement from FDA and approval from the NIH IRB, we can share the specific details of the initial clinical trial, such as patient inclusion/exclusion criteria.
We are very excited about the progress we have made thus far and are encouraged by our recent meetings with FDA. We understand that the community is eager to start this initial trial as soon as possible and we do not have time to waste. Following the meeting, we believe that FDA shares our sense of urgency and we are grateful that they are willing to work closely with us to get this important initial trial started. As always, your support of NPC research is the final piece that will help us impact this disease. Thank you for your enthusiasm, your patience, and especially for trusting that we are making every effort to help individuals and families affected by NPC.
The TRND Team
[Dec 16, 2011 mem]
Update -- Upcoming Cyclodextrin Trial
Follow this link to read the November 4th, 2011, announcement: Cyclodextrin Trial Update 11-4-11
Members of the NPC Team. Photo taken on Nov 1, 2011, at an update meeting with the FDA.
Front row (left to right): Ilona Scott (J&J), Pat Frenchick (RRD), Sandie Morseth (RRD), Kimberly Lilly (RRD), Mark Kao (J&J), Nicole Yanjanin (NIH/NICHD), Liz Ottinger (NIH/TRND), Nuria Carrillo-Carrasco (NIH/TRND), Xin Xu (NIH/TRND)
[Nov.4, 2011 nmh]
2012 WORLD Symposium Set for February 8 - 10
San Diego, California
The major educational activity of the Lysosomal Disease Network (LDN) has become the WORLD™ Symposium (WORLD -- We’re Organizing Research for Lysosomal Diseases), an annual activity with the first day focused on “basic research,” the second day on "translational research,” and the third on “clinical trials.”
In addition to serving the annual meeting of the LDN membership, this 8th WORLD™ Symposium 2012 will provide a multidisciplinary forum to present and discuss basic, translational, and clinical research, thus fostering innovative treatment for these diseases. This meeting platform promotes the sharing of basic and clinical science advances for all lysosomal diseases, and provides an opportunity to discuss the related treatment outcome issues. The symposium is open to physicians, scientists, patients, pharmaceutical industry, and others interested in lysosomal disorders.
NEW THIS YEAR: Lysosomal Diseases 101 --
Tuesday, February 7, 2012, 1pm-5pm
The Lysosomal Diseases 101 course will provide a foundation for researchers and health care practitioners who are interested in gaining more background on the diagnosis and treatment of lysosomal diseases. This course will cover accepted methods of diagnosis and treatment of the known lysosomal diseases. This course will not cover any new or ongoing research. This course will be taught at the graduate-student level and is targeted towards those who would like to learn more of the fundamental information that provides the basis for future research and treatments, as well as those who would benefit from a refresher on this topic.
Place: Manchester Grand Hyatt, San Diego, California, USA
Sponsoring organization: University of Minnesota’s Office of Continuing Medical Education
Co-presented by: the Lysosomal Disease Network and the National Institutes of Health (NIDDK, NINDS, & ORD)
[Nov 8, 2011 mem]
NPC Researchers' Work Highlighted in
Journal of Biological Chemistry
A paper authored by Andrew Munkacsi, Ph.D., et al, was selected as Paper of the Week by the Journal of Biological Chemistry earlier this summer. Dr. Munkacsi is the NNPDF's newest Peter G. Pentchev postdoctoral fellow, studying Niemann-Pick Disease at Columbia University. Additional authors include Yiannis A. Ioannou, Ph.D. and Steve Sturley, Ph.D., both members of the NNPDF's Scientific Advisory Board.
Cruel to Be Kind: Genomic Exacerbation of Lipid Defect in Yeast Suggests New Therapy for a Pediatric Neurodegenerative Disease - An “Exacerbate-reverse” Strategy in Yeast Identifies Histone Deacetylase Inhibition as a Correction for Cholesterol and Sphingolipid Transport Defects in Human Niemann-Pick Type C Disease - see the Journal of Biological Chemistry's Web page for more information.
[Oct 3, 2011 mem]
Ebola Research finds Link to NPC1 Protein
Two recent publications from researchers based at MIT and Harvard report that the NPC1 protein is an essential factor in allowing infection by the deadly Ebola virus. The MIT team lead by Brummelkamp et al. used a genetic screen to identify mutant cells that were unable to support Ebola infection. They identified a panel of genes related to uptake into endosomes, most notably NPC1. Cunningham and colleagues at Harvard used small molecule inhibitors to prevent Ebola infection, and in collaboration with Dan Ory at Washington University, demonstrated that the inhibitors were disrupting interaction between a viral protein and NPC1. These findings lay the groundwork for development of new drugs to prevent Ebola infection. The studies will spur further interest in the NPC1 protein, and could lead to new insights into its function.
Links to the articles appear below:
[Sept 6, 2011 mem]
Major Breakthrough in Amyotrophic Lateral Sclerosis
Findings Could Affect Research into Other Diseases of Dementia
Northwestern University recently reported on a major breakthrough in research on Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's Disease. The findings could have ramifications for future research into Niemann-Pick Disease as well as other diseases with elements of dementia.
[Sept 6, 2011 mem]
The Michael, Marcia, and Christa Parseghian Scientific Conference for Niemann-Pick Type C Research was held June 9th -11th at Notre Dame University. Researchers, physicians, and parents of NPC children came together from all over the world to attend this scientific conference to share Niemann-Pick Type C research project results and related information.
The NNPDF Board was represented by Karen Quandt and Nicole Yanjanin, the NNPDF Scientific Advisory Board was represented by Drs. Ory, Porter, Liscum, Pentchev, Sturley and Vance . The NNPDF-sponsored research fellows, Dr. Fabrizio Vacca and Dr. Nick Cianciola, presented their research projects to the group.
The summary of the Scientific Conference was written by Dr. Pam Tamez and Dr. Kasturi Haldar from the Center for Rare and Neglected Diseases at the University of Notre Dame.
[July 1, 2011 mem]
Two independent studies suggest a new pathway for intervention in NP-C disease that is FDA approved for treatment of other diseases. Here, senior authors of these papers, Dr. Sturley (long-time member of the NNPD's Scientific Advisory Board) and Dr. Fred Maxfield, describe their findings and optimistically but cautiously describe the potential of this strategy as a therapy.
The modification of proteins after they are synthesized is a common and critical regulatory aspect of many cellular processes. Acetylation of proteins such as histones, changes their net charge from positive to neutral or negative. This reduces the ability of the histone to associate with DNA and thus changes the expression of numerous genes. The removal of acetylation (i.e. histone deacetylation, HDAC), reverses this effect. Treatment of human cells derived from NP-C patients, with HDAC inhibitors markedly improves cholesterol (1, 2) and sphingolipid (2) abnormalities of these cells. These observations were made with newer HDAC inhibitors that can be used at concentrations 1000-fold lower than that suggested for valproate, which reportedly was ineffective in some NP-C patients. One HDAC inhibitor is currently FDA-approved for treatment of cancer. Several others are in clinical trials for cancer and other diseases, including neurodegenerative conditions such as Huntington’s disease and ALS. Because of the existing safety testing and evidence of entry into the brain, there is the potential to enter into the clinic with these leads relatively quickly. However, several critical issues still need to be addressed. For example, it appears that the mechanism may be related to increased expression of the NPC1 protein (1). Consequently, it is not yet known which mutations (i.e. which patients) will respond effectively to HDACi treatment. Most importantly we need to determine if these compounds affect the function of the brain in NP-C patients or animals. Studies to address these issues are in progress.
1. Pipalia NH, et al. (2011) Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts. Proc Natl Acad Sci U S A 108(14):5620-5625.
2. Munkacsi AB, et al. (2011) An “Exacerbate-reverse” Strategy in Yeast Identifies Histone Deacetylase Inhibition as a Correction for Cholesterol and Sphingolipid Transport Defects in Human Niemann-Pick Type C Disease. J. Biol. Chem. 286. Abstract
[July 1, 2011 mem]
Wall Street Journal Health Blog Article:
In an article by Amy Dockser Marcus, the Wall Street Journal's Health Blog reported on a paper recently published in the Journal of Neuroscience on the use of cyclodextrin to treat NPC in mice. The paper's authors, led by Dr. John M. Dietschy of the University of Texas Southwestern Medical School, report that the treatment not only kept the mice alive, but prevented the cognitive decline of NPC.
“It will be a very influential paper in the field,” scientist Daniel Ory [Chair of the NNPDF's Scientific Advisory Board] tells the Health Blog. Ory ought to know: he is the principal investigator on an NIH grant focused on getting cyclodextrin from the lab into NPC patients. He’s also working closely with NIH’s Therapeutics for Rare and Neglected Diseases program, which selected NPC and cyclodextrin as one of its pilot projects to attempt to repurpose drugs for use in rare diseases.
The NNPDF hosted a conference call on May 2 which addressed plans for an upcoming clinical trial using cyclodextrin in NPC patients. In addition to Dr. Ory, the conference call included information about the clinical trial from Dr. Forbes "Denny" Porter of the National Institutes of Health. Text of the conference call (pdf).
[June 23, 2011 mem]
Here are several updates regarding Niemann-Pick Disease research:
Sandra Cowie, OT, Director-at-Large for the NNPDF, attended the 2011 WORLD Symposium in February. She reports that there were five sessions dealing with Niemann-Pick Disease (four on NPC and one on ASMD), and a poster presentations display area. Sandra wrote this report to share the information and updates from the conference.
Ian Williams, Ph.D., attended the renowned Gordon Research Conference and filed this report. Dr. Williams is one of our NNPDF-funded postdoctoral fellows working on his research project titled Neurobiology of Purkinje Cells in NPC1.
We also now have available a text document of the NPC updates presented during the May 2nd conference call/Webinar. Anyone who was not able to participate in the meeting, and those who would like to review the information presented, can click here for a PDF of the document. A recording of the meeting is also available for a limited time. Visit our special page for instructions to access the recording via telephone or computer.
Thank you, Sandy, and Drs. Williams, Ory, Porter, Patterson and Austin, for participating in thess important updates for our families!
[May 19, 2011 mem]
Europe's largest stem cell clinic shut down after death of baby
Europe's largest stem cell clinic has been shut down after the death of a baby who received an injection into the brain. The closure of the XCell-Centre in Dusseldorf, German, follows an undercover investigation into its controversial practices, allowed by a loophole in German laws allowing the center to charge for the experimental procedures.
Most other European countries, along with the U.S., Canada and Australia, have banned stem cell treatments unless proven to be safe and effective.
Read the article by Robert Mendick and Allan Hall, posted by The Telegraph on May 18.
[May 18, 2011 mem]
NIH to Develop Clinical Trial Utilizing Cyclodextrin
The National Institutes of Health (NIH), in collaboration with the Therapeutics for Rare and Neglected Diseases Program (TRND), is developing a clinical trial utilizing cyclodextrin for Niemann-Pick Type C patients.
The clinical trial is in the planning phase and many criteria must be met and numerous approvals granted before the trial can take place. Dr. Forbes "Denny" Porter, a Senior Investigator at the NIH, and Dr. Daniel Ory, NNPDF Scientific Advisory Board Chair, are working collaboratively to bring this trial to our NPC patient community.
SAVE THE DATE
On May 2 , the NNPDF will host a conference call with key constituents and researchers, for all interested parties in the NPC community to learn more about the work being done at the NIH. This conference call will include information pertaining to the development of plans for a cyclodextrin trial.
Please visit our Cyclodextrin Clinical Trial page for more details about the conference call.
Updates at the 2011 Family Support and Medical Conference
Further updates on the clinical trial will be presented at the NNPDF Family Support and Medical Conference in Norfolk, Virginia, July 28th - 31st. Dr. Porter and Dr. Ory will answer questions pertaining to the clinical trial and will update us about the trial at the conference.
[Apr 7, 2011 mem]
A paper regarding a study into Niemann-Pick Disease Type C (NPC) was published in a recent issue of Proceedings of the National Academy of Sciences (PNAS). The paper, coauthored by Olaf Wiest and Paul Helquist of the University of Notre Dame and Frederick Maxfield of Cornell University, says the use of a histone deacetylase inhibitor corrects the damage done by the genetic disorder NPC and allowed once-diseased cells to function normally.
Follow this link to read the paper's abstract at PNAS: http://www.pnas.org/content/early/2011/03/15/1014890108. Follow this link to read the Notre Dame press release dated March 21, 2011: http://www.eurekalert.org/pub_releases/2011-03/uond-bin032111.php
For help in understanding this information, the NNPDF consulted three respected experts in Niemann-Pick Disease Type C: Dr. Dan Ory of Washington University, Dr. Marc Patterson of Mayo Clinic, and Dr. Forbes "Denny" Porter of the National Institutes of Health.
Daniel Ory, M.D., Washington University School of Medicine, and Chair of the NNPDF’s Scientific Advisory Board, responded to our inquiry:
The results are promising, but represent an early step in the process of identifying effective compounds for NPC. More cell studies are needed to understand the mechanism [and] mouse studies should be pursued….there is a long history of compounds that are effective in reducing cholesterol in cultured cells but do not have benefits in animal models, so we should be cautious in extrapolating such results to humans.
Marc C. Patterson, M.D., Chair of the Division of Child and Adolescent Neurology at Mayo Clinic, also a member of the NNPDF’s SAB, further cautioned against making premature assumptions:
The work was done in cultured fibroblasts, so one should be very cautious about extrapolating these data to animals or humans. Moreover, the work was done in cells expressing one or two I1061T NPC1 mutations, and may not be relevant to other mutations; it was not effective in an NPC2 mutant cell line. Of note, the late Dick Pagano showed dramatic reversal of trafficking abnormalities and filipin staining in NPC fibroblasts in which rab 7 and 9 were overexpressed, but much more modest results in transgenic mice with NPC1 mutations and rab overexpression.
Mouse studies could certainly be justified, but it would be premature to assume that this approach will be applicable in humans with NPC.
Another of the NNPDF's SAB members, Forbes “Denny” Porter, M.D., Ph.D., of the National Institute of Child Health and Human Development at the National Institutes of Health (NIH), stated, “It is always good news to have a potential new approach to treating NPC. Cells are the starting point, but to translate this to a potential therapy more work needs to be done.”
Histone deacetylase inhibitors (referred to as HDAC inhibitors) are a class of compounds that interfere with the function of histone deactylase. HDAC inhibitors have a history of use in psychiatry and neurology as mood stabilizers and anti-epileptics.
One HDAC inhibitor, valproic acid, was considered as a possible treatment for NPC, but results have not been overly promising.
Yiannis Ioannou, Ph.D., Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine, also a member of the NNPDF’s SAB, made the following statement regarding his recent study of valproic acid and NPC:
We have just concluded our mouse studies on valproic acid and have evaluated its effect on cells from a number of NPC patients and on the NPC mouse. Unfortunately, the results are not great.
For NPC patient cell lines we have treated six different lines with valproate. Some cells responded positively; i.e., the cholesterol storage was cleared but some lines were completely resistant to the treatment. Upon analysis of our data it became clear that if the patient has a relatively mild mutation then they would respond to valproate, whereas if the mutation is more severe, then the cells don’t respond.
With respect to the mouse study, we have treated about 25 mice with daily dosing of valproate. We can extend the life of these mice by about 10%. The mice live about 122 days on average vs. 108 days for the untreated mice.
At this point we don’t think that valproic acid would be beneficial for NPC patients.
Some years ago, valproic acid was given to a few NPC patients, including Stacey Vorpahl (1985-2004), the daughter of Gary and Barbara Vorpahl of Fort Atkinson, Wisconsin for the treatment of seizures. Barb, Vice Chair of the NNPDF Board of Directors, recently posted to the NNPDF listserv group about her family’s experience with valproic acid (as Depakote):
We did have Stacey on valproic acid (Depakote) for seizures when she first started having seizures. This was at age seven. Once she started Depakote we saw a rapid decline. One of the side effects is muscle weakness. It can also actually cause seizures at higher doses. She was on Depakote for about a year. She quit talking, needed a wheelchair, could no longer sit up or roll over by herself. We didn’t think she would survive to age 8 at her rate of deterioration. We thought the decline was from NPC but after comparing notes with other parents and seeing strange seizures that their children were also experiencing when doses were increased, we decided to gradually wean her off of Depakote and try another seizure medication. It was like bringing her back from the dead. We saw her strength start coming back, alertness level [sic], her talking never resumed but she did have strength to walk with assistance. I know others have had success with valproic acid but for Stacey it was a very negative experience. I was very surprised when I saw research coming out on valproic acid. It may work in mice but it certainly did not help our daughter even controlling seizures.
This summary was compiled by the NNPDF Central Office staff with thanks to the members of our esteemed Scientific Advisory Board. (March 31, 2011)
The National Niemann-Pick Disease Foundation (NNPDF) does not engage in the practice of medicine. It is not a medical authority nor does it claim to have medical knowledge. This site is an educational service of the National Niemann-Pick Disease Foundation and is not meant to provide diagnostic or treatment advice. Information contained or suggested on this Web site does not constitute medical advice. For all information related to care, medication or treatment, the NNPDF recommends consulting a physician to determine if information presented is applicable. Please review these additional cautions about medical information provided on the Internet.
[April 5, 2011 mem]
|NIH Director, Dr. Francis S. Collins|
NIH Director Dr. Francis Collins was the featured guest of a recent Webinar designed to separate fact from fiction about the proposed National Center for Advancing Translational Sciences. Over 600 Webinar participants included members of patient advocacy groups, medical research foundations and other stakeholders in the medical research system.
Niemann-Pick Disease Type C (NPC) was featured as an example of a rare disease that could benefit from NCATS.
The hour-long Webinar is archived and available for viewing here. It is also available via a link at the Web site of FasterCures (The Center for Accelerating Medical Solutions) at http://www.fastercures.org/train/tools/webs.html.
[Mar 17, 2011 mem]
The NNPDF invites applications for the 2011 Peter G. Pentchev Postdoctoral Fellowships. These fellowships provide funding for research projects studying the biology of Niemann-Pick Type C (NPC) disease.
M.D., Ph.D., and D.V.M. postdoctoral fellows are eligible to apply for funding to improve understanding of the biology and pathogenesis of NPC. Preference will be given to research projects developing new therapies for NPC, and identifying biomarkers of disease activity for diagnosis and clinical trials.
The fellowships provide support of $50,000 per annum for two years and may be renewable based on performance. Applications are due May 1, 2011.
[Mar 9, 2011 mem]
RRD International, a strategy-driven biotech and pharmaceutical product development company, has entered into a partnership with the National Institutes of Health (NIH) Therapeutics for Rare and Neglected Diseases (TRND) program as a regulatory support and development partner.
The RRD and TRND partnership will focus on two rare disease drug development projects: Niemann-Pick Type C1 Disease (NPC1), and Hereditary Inclusion Body Myopathy (HIBM), a rare adult-onset neuromuscular disorder.
As a new program, TRND is intended to advance preclinical and early clinical development of new drugs for rare and neglected diseases. The program is designed to speed development of new drugs that might otherwise fall by the wayside. For more information, read the press release about RRD - TRND partnership.
[Mar 2, 2011 mem]
Dr. Daniel Ory, M.D., Washington University School of Medicine, and chair of the NNPDF’s Scientific Advisory Board (SAB), gave updates on the latest research into Niemann-Pick Disease Type C at the recent NNPDF annual board meeting.
Dr. Ory reported that this is an exciting time for research, and he is optimistic about the future with strong research projects working to unlock the mysteries of NPD. Dr. Ory thanked the NNPDF for its continuing support of the research which is so essential to finding effective treatments for NPD.
Read the summary of Dr. Ory’s updates.
[Feb 25, 2011 mem]
Update from Jamie Manganello, Director, Patient Advocacy, at Genzyme:
Genzyme and sanofi-aventis have entered into an agreement under which sanofi-aventis will acquire Genzyme. Sanofi-aventis is a global, diversified healthcare company, headquartered in Paris, France and a leader in diabetes, oncology, innovative medicines, vaccines, consumer health care products and animal health. With this transaction, Genzyme will move into a new phase of our development, continuing our patient-focused mission and developing treatments that change the lives of people with rare diseases.
Sanofi-aventis and Genzyme have a shared vision for our future together and believe we will emerge even better prepared to serve you. The plan is for Genzyme to become a division of sanofi-aventis and global center of excellence for rare diseases. We will continue to serve the rare genetic disease community as we have done for the past 30 years, and I believe that sanofi-aventis will bring important new perspectives and new resources to this work.
Until the transaction closes, which is expected early in the second quarter of this year, both companies remain independent. Every aspect of how we work and our commitment to you remain the same.
In partnership with you, Genzyme’s mission has always begun and ended with the patient. Sanofi-aventis is making a significant investment in Genzyme because they value what we do, and our mission will remain unchanged.
As we work through the details, we will share our progress with you. Our future is dependent upon the support and involvement of patients and the treatment community, and we are eager to hear your thoughts and feedback as well.
Thank you for your continued support of Genzyme, and we look forward to updating you soon on our progress and path forward.
[Feb 16, 2011 mem]
A new DNA test has been developed to identify carriers of 580 of the most severe inherited childhood diseases. Announced in the journal Science in Translational Medicine, the test uses genetic sequencing to identify recessive mutations.
The new test could be used before a couple decides to become parents. Currently, preconception testing is recommended for just a few diseases, such as Tay-Sachs and cystic fibrosis, and can cost as much as $2,000.
According to abcnews.go.com, this new carrier screening may cost less than $400, and may become available in the near future. Clinical work will be done at Children's Mercy Hospital in Kansas City, Missouri. The test will likely be a blood test and later a simple swab of the cheek. Egg and sperm banks may be the first industry to adopt the testing to screen potential donors.
For more information, see the ABC News article here.
[Jan 25, 2011 mem]
The NIH Rare Diseases Clinical Research Network (RDCRN) comprises 19 consortia involving some 80 investigators at over 70 academic institutions. This program and its Data Management Coordinating Center (DMCC) are receiving an aggregate total of $117 million over five years. The research conducted with the new funding will explore the natural history, epidemiology, diagnosis, and treatment of more than 95 rare diseases
Initially created in 2003, the RDCRN is unique in its approach to addressing disease. Previously, the NIH's institutes and centers funded research on individual rare diseases. The RDCRN is the first program that aims to create a specialized infrastructure to support groups of rare diseases that are related.
Since its creation, the RDCRN has enrolled over 6,600 patients into 48 clinical studies in rare diseases.
To read more about the RDCRN, visit: http://rarediseasesnetwork.epi.usf.edu/spotlight/december2010/rdcrn2.htm
[Dec 9, 2010 mem]
The NIH Rare Diseases Clinical Research Network (RDCRN) has launched a quarterly e-newsletter to highlight the mission and dynamism of the RDCRN. Visit the link below to see the December 2010 issue of Spotlight on Rare Diseases.
[Dec 9, 2010 mem]
Molecular Genetics and Metabolism recently published a new article titled, "Oxidative stress in Niemann-Pick disease, type C," from authors Fu R, Yanjanin NM, Bianconi S, Pavan WJ, Porter FD.
The article is summarized as follows:
Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to detoxify the reactive intermediates or easily repair the resulting damage. Increased oxidative stress has been reported in human NPC1 mutant fibroblasts and in tissues from Npc1 mutant mice. However, oxidative stress in NPC patients has not been established. This study demonstrated increased oxidative stress in NPC patients.
Blood samples from 37 children and adults with NPC were tested. Compared to control values, the NPC samples showed significant decreases in both the fraction of reduced coenzyme Q10 (CoQ10) and Trolox equivalent antioxidant capacity (TEAC). Reduced CoQ10 functions as an antioxidant protecting cells from oxidative damage. Trolox is used as a reference substance to measure the combined antioxidant capacity in biological specimens. Both findings are consistent with increased oxidative stress in NPC. However, supplementation with CoQ10 was not effective in correcting the decreased fraction of reduced CoQ10. Demonstration of increased oxidative stress in NPC patients provides both a rationale and the biomarkers necessary to test the efficacy of antioxidant therapy in NPC.
[Nov 19, 2010 mem]
Dr. Fabrizio Vacca and Dr. Ian Williams have provided us with updates on their research projects currently underway:
Fabrizio Vacca, Ph.D.;
Sponsor: Professor Jean Gruenberg;
(University of Geneva, Switzerland)
Analysis of cholesterol export from purified endosomes in NPC cellular models
Lay Summary with Sept 2010 Update
Ian Williams, Ph.D.;
Sponsor: Professor Fran Platt;
(University of Oxford, UK)
Neurobiology of Purkinje Cells in NPC1
Lay Summary with Sept 2010 Update
Click here to read about the projects of our two newest fellows, Drs. Nicholas Cianciola and Dorothea Maetzel.
[Nov 12, 2010 mem]
Niemann-Pick Disease Type C (NPC) may soon be diagnosed with a simple blood test, according to a report from the Washington University School of Medicine, St. Louis, Missouri, published recently in Science Translational Medicine.
Dr. Dan Ory of Washington University, and the chair of the NNPDF's Scientific Advisory Board (SAB), is one of the report's authors, along with Dr. Forbes "Denny" Porter, of the National Institutes of Health (NIH), also on the NNPDF's SAB; and Nicole Yanjanin, R.N., NIH, and on the NNPDF's Board of Directors; and others.
Visit Newswise for the complete story and video clip, which features Dr. Ory along with Nancy and Art Sullivan, parents of Karen Sullivan, who passed away from NPC in 2004, at the age of 33.
[Nov 4, 2010 mem]
The Ara Parseghian Medical Research Foundation (APMRF) Conference was held in Tucson, Arizona, in late September, bringing together Niemann-Pick Disease Type C (NPC) researchers, physicians, parents and organizations. Click here to view the conference agenda.
Suzanne R. Pfeffer of the Stanford University School of Medicine, Department of Biochemistry, provided us with this APMRF Scientific Conference Overview.
The APMRF conference abstracts, with additional notes by NNPDF Board Chair Karen Quandt, are available here.
The NNPDF holds the greatest respect and gratitude toward the APMRF (Cindy Parseghian, President) and the NPC research advancements it has spearheaded over the years. The work of all involved at the APMRF has opened many doors and established new and innovative ways to encourage more communication between scientists.
The APMRF has been instrumental in bringing together NPC researchers from around the world to share in their knowledge and findings. In addition, the foundation has played an integral part in drawing new researchers into the NPC scientific field. Without these efforts much of the progress we have seen in NPC would not have occurred.
We are all truly grateful for the work of the APMRF and the entire Parseghian family in memory of their children ~ Michael, Marcia and Christa.
For more information about the APMRF, please visit their Web site at http://www.parseghian.org
[Oct 14, 2010 mem]
The Institute of Medicine (IOM) recently released a report calling for implementing an integrated national strategy to promote rare diseases research and product development. The report, Rare Diseases and Orphan Products: Accelerating Research and Development, is the result of a two-year study commissioned by the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). The full text of the report is available here or on the IOM website .
The NNPDF is pleased to announce the recipients of the 2010 Peter G. Pentchev Postdoctoral Research Fellowships.
The research projects of Dr. Nicholas Cianciola of Case Western Reserve University, and Dr. Dorothea Maetzel of the Whitehead Institute for Biomedical Research, were selected through an application process which included reviews by the NNPDF's Scientific Advisory Board (SAB). The SAB then made recommendations to the NNPDF's Research Committee and Board of Directors.
Dr. Dan Ory, Chair of the NNPDF's Scientific Advisory Board summarized the two selected projects:
1. Nicholas Cianciola - "Activation of an alternative cholesterol homeostatic mechanism in NPC"
Dr. Cianciola’s project builds upon an exciting observation he made while a graduate student and will explore the role of a viral protein in facilitating movement of cholesterol from lysosomes. The research has the potential to identify new therapeutic targets to stimulate release of cholesterol from lysosomes in the absence of a functional NPC1 protein.
Dr. Cianciola's sponsor at the School of Medicine, Case Western Reserve University (Cleveland, OH) , is Professor Cathleen Carlin.
To read Dr. Cianciola's Lay Summary of the project, click here.
2. Dorothea Maetzel - "In Vitro modelling of Niemann-Pick type C Disease Using Patient-Specific Induced Pluripotent Stem Cells"
Dr. Maetzel’s project will lead to development of pluripotent stem cells from human NPC mutant fibroblasts. The stem cells will then be used for high throughput assays to identify small molecules that can correct the cholesterol accumulation in the NPC cells. Development of these cell lines will allow allow testing of whether the genetic defect can be corrected in the stem cells, which could have therapeutic potential.
Dr. Maetzel's sponsor at the Whitehead Institute for Biomedical Research (Cambridge, MA) is Dr. Rudolf Jaenisch.
To read Dr. Maetzel's Lay Summary of the project, click here.
The fellowships are named for Peter G. Pentchev, Ph.D., Emeritus Scientist. Dr. Pentchev's career was as a senior research scientist at the National Institute of Neurological Disorders and Stroke (NINDS). To read a tribute to Dr. Pentchev from NNPDF Board Member Barb Vorpahl, click here.
Congratulations to Drs. Cianciola and Maetzel, and many thanks for your work to advance Our Quest for a Cure!
[Sept 14, 2010 mem]
On Wednesday, July 21, the US Senate Committee on Health, Education, Labor, and Pensions held a hearing entitled, "Treating Rare and Neglected Pediatric Diseases: Promoting the Development of New Treatments and Cures."
A panel at the hearing featured Dr. Jesse Goodman, chief scientist at the FDA, and Dr. Alan Guttmacher, the new director of the National Institute of Child Health and Human Development of the National Institutes of Health. A second panel included representatives from various non-governmental organizations.
Participants advocated for a range of solutions, including increased federal funding for clinical registries, more stringent guidelines for patient registries, and establishing a federal policy in regards to orphan drugs and rare diseases; all of which would have an ultimate goal of encouraging researchers to develop drugs for those rare diseases that currently have none.
For more information and a video, visit: http://help.senate.gov/hearings/hearing/?id=d132692d-5056-9502-5da9-23c77808a20f
[Sept 1, 2010 mem]
We have had quite a bit of discussion on our listserv pertaining to the recent research and treatment options for Niemann-Pick Type C (NPC) Disease.
To provide some background and insight for these continuing discussions, we have compiled a summary of the presentation abstracts from the "Promising Therapies for Niemann-Pick Type C Disease" meeting sponsored by the National Institute of Neurological Disorders and Stroke (a division of the US National Institute of Health) in Rockville, Maryland, June 3-4.
[July 9, 2010 mem]
Niemann-Pick Type C Pathogenesis and Treatment: From Statins to Sugars
Moneek Madra and Stephen L. Sturley
A paper titled Niemann-Pick type C pathogenesis and treatment: from statins to sugars was recently published. The paper is by Moneek Madra, Department of Pediatrics, and Stephen L. Sturley, Institute of Human Nutrition, both of Columbia University Medical Center in New York, New York. Click here for the article summary.
[June 9, 2010 mem]
FDA grants “Orphan Drug Designation” to Cyclodextrin for treatment of
Niemann-Pick Disease Type C
Due to the efforts of Hugh and Chris Hempel, Dr. Caroline Hastings and Ron Browne, an application to the Food and Drug Administration requesting “Orphan Drug Status” for Cyclodextrin has been approved.
What exactly does that mean for our NPD community? It is important to emphasize that an Orphan designation does not make any assessment at all on how the drug works in clinical trials, whether it is safe or effective in patients, nor whether it will ever be commercially available – the Orphan designation’s main purpose is to make the development of the drug more financially viable for the developer.
Please visit our cyclodextrin page for a bit of background and glossary terms that will help you to understand this latest development.
[May 25, 2010 mem]
Are Stem Cells or Gene Replacement Viable Therapies for NPC?
April 13, 2010: In response to recent questions from NPC families, the NNPDF asked Dr. Dan Ory, Chair of the Foundation's Scientific Advisory Board, about the possibility of using either stem cells or gene replacement as therapies for Niemann-Pick Disease Type C.
Here is Dr. Ory's response:
I know of no evidence that gene replacement therapy is effective for NPC disease. There may be work going on in this area, but there is nothing promising on the horizon.
[ Re. the suggestion ]... that stem cell therapy is efficacious in the NPC1 mouse model... I am not aware of this. In fact, in my own lab I replicated the experiments done by labs claiming to show benefit from stem cell transplantation, only to find that the protocols actually worsened symptoms and shortened the life span of the mice. Any claim that with our current technology that stem cell transplantation is beneficial should be met with extreme skepticism.
[Apr 15, 2010 mem]
Report from WORLD Meeting
Cate Walsh Vockley, NNPDF Coordinator of Education, Referral and Advocacy, recently returned from the 2010 WORLD (We're Organizing Research for Lysosomal Diseases) meeting.
Click here to read Cate's summary of the meeting's sessions.
[Mar 17, 2010 mem]
NIH and FDA Announce Collaborative Initiative
Partnership to Speed New Treatments to Patients
The U.S. Food and Drug Administration and the National Institutes of Health have announced an initiative intended to accelerate the timeline between scientific breakthrough and the availability of innovative medical therapies to patients.
From the NIH's press release:
The initiative involves two interrelated scientific disciplines: translational science, the shaping of basic scientific discoveries into treatments; and regulatory science, the development and use of new tools, standards and approaches to more efficiently develop products and to more effectively evaluate product safety, efficacy and quality. Both disciplines are needed to turn biomedical discoveries into products that benefit people.
As part of the effort, the agencies will establish a Joint NIH-FDA Leadership Council to spearhead collaborative work on important public health issues. The Joint Leadership Council will work together to help ensure that regulatory considerations form an integral component of biomedical research planning, and that the latest science is integrated into the regulatory review process.
Click here to read the entire press release.
[Mar 5, 2010 mem]
United States FDA Advisory Committee Backs Use of Zavesca for NPC
Significant Step Toward Possible FDA Approval
An advisory committee comprised of medical and clinical experts will recommend to the U.S. FDA that Zavesca (miglustat) be approved for use in Niemann-Pick Disease Type C (NPC) patients. The advisory committee reviewed data and heard statements and testimony from scientists, doctors and NPC families in a daylong review January 12.
If the FDA approves the use of Zavesca for NPC, it will be an historic step, as this would be the first authorized treatment for the symptoms of NPC in the United States.
[Jan 13, 2010 mem]
More Details on Cyclodextrin from Dr. Dietschy's Lab
Work continues in Dr. John Dietschy's lab at UT Southwestern (Texas), aimed at understanding the way cyclodextrin works in NPC cells and the effect of its administration at various stages of disease in the NPC1 mouse. A recent paper shows reversal of cholesterol storage and decreased inflammation in a variety of tissues 48 hours after administration of cyclodextrin. However, lifespan of the NPC1 mouse is extended only following very early administration of the compound. Research continues.
For more details, visit: http://www.jlr.org/cgi/rapidpdf/jlr.M000257v1
[Dec 21, 2009 mem]
Adenovirus RID- activates an autonomous cholesterol regulatory mechanism
that rescues defects linked to Niemann-Pick disease type C
An adenovirus membrane protein called RID-α (RID-alpha) may provide a route to bypass the lipid-sorting defects in cells of patients who have NPC by providing an alternate pathway for cholesterol trafficking.
Learn more at:
[Dec 21, 2009 mem]
Stem Cell Derived Neurons for Research Relevant to
Alzheimer's and Niemann-Pick Type C Diseases
Work being done in the lab of award-winning scientist Dr. Lawrence Goldstein at the University of California, San Diego, looks at the relationship between Niemann-Pick disease, type C and Alzheimer disease. Failure of proper transport of proteins, lipids and other materials may play a significant role in the cell breakdown and death in these 2 diseases. To learn more, click the following link: http://www.sciencedaily.com/releases/2009/12/091209134627.htm
[Dec 21, 2009 mem]
Edinburgh Neuroscience Christmas Lecture 2009
While the following link will take you to a fairly technical overview , for those who are interested in the potential for stem cell therapies, it is a fascinating lecture. Two University of Edinburgh, Scotland, professors provide a review of the current status of developments in stem cell research and future applications to clinical medicine. Their focus is on neurological disorders such as Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig disease) and Parkinson disease. Their initial work focuses on study of genes that are active in regenerating brain tissue, something that does happen, but which becomes less efficient with age. They look at targeting expression of these genes through use of medications in order to carry out brain repair. They also look at use of stem cells, both embryonic stem cells and those created from adult cell lines. Note that this is an overview and some issues, such as the difficulties encountered with aging of "embryonic" stem cells produced from adult cells, are not discussed.
[Dec 21, 2009 mem]
New Postdoctoral Research Fellowships
The NNPDF is very pleased that contracts have been finalized for the first two Peter G. Pentchev Research Fellowships. Visit our Current and Recent Research Grants page for links to read the lay summaries of fellows Dr. Ian Williams and Dr. Fabrizio Vacca.
[Dec 18, 2009 mem]
U.S. Food and Drug Administration Grants Priority Review for Zavesca
Committee Discussion Scheduled for January 12, 2010
A press release issued by Actelion Ltd, makers of Zavesca (miglustat), announced that a supplemental new drug application for an extension of indication for Zavesca for the treatment of progressive neurological manifestations in NPC has been accepted by the U.S. Food and Drug Administration (FDA).
Further, the FDA has granted Zavesca a priority review designation, given to drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists. It also means that the FDA will aim to complete the review within six months. Read the full press release here.
On January 12, 2010, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee will discuss new drug application (NDA) 21–348, ZAVESCA (miglustat), 100 milligram (mg) capsules, by Actelion Pharmaceuticals, Ltd., proposed for the treatment of progressive neurological manifestations (symptoms related to the nervous system) in patients with Niemann-Pick Disease (type C). Read more, including how you can submit a written statement or make an oral presentation to the committee, here: http://www.fda.gov/AdvisoryCommittees/Calendar/ucm191156.htm
[Dec 1, 2009 mem]
Research from the lab of Drs. Michael Brown and Joseph Goldstein was recently published online (in advance of print publication) in a highly regarded
scientific journal, The Proceedings of the National Academy of Science. The abstract, or summary, of the work is available at:
The paper provides details about the processing of cholesterol in NPC1-deficient cells if it can be released from the lysosomes, and about how cyclodextrin assists in moving cholesterol out of the lysosome and into the cell cytoplasm, where they hypothesize that it will be less damaging to cell function.
The authors note that additional study is needed to understand
whether there are specific conditions under which the cyclodextrin works to
move cholesterol, and the specific way it works, which is not yet
[Nov 16, 2009 mem]
Psychosocial Aspects of Niemann-Pick Disease, Type B
Dr. Wendy Packman, et al.
A new research article titled, "Psychosocial Aspects of Patients with Niemann-Pick Disease, Type B," was published recently in the online American Journal of Medical Genetics. The article is by Dr. Wendy Packman and colleagues.
For more information, including the abstract, please click here.
[Nov 16, 2009 mem]
New Paper from Dr. Wraith and Jackie Imrie
"New therapies in the management of Niemann-Pick type C disease: clinical utility of miglustat"
A new paper by Dr. James E. "Ed" Wraith and Jackie Imrie, regarding Miglustat (Zavesca) and NPC, was published recently. Please visit Dovepress to read the abstract and the complete document.
[Nov 10, 2009 mem]
"An international team led by a National Institutes of Health researcher has found that carriers of a rare, genetic condition called Gaucher disease face a risk of developing Parkinson’s disease more than five times greater than the general public. The findings were published ... in the New England Journal of Medicine.
In previous studies, several genes have been linked to Parkinson's disease. However, researchers say their work conclusively shows that mutations in the gene responsible for Gaucher disease are among the most significant risk factors found to date for Parkinson's disease. The discovery was made by investigators from the National Human Genome Research Institute (NHGRI) and the National Institute on Aging (NIA), both parts of the National Institutes of Health, in collaboration with scientists from 16 research centers across four continents.
'This analysis illustrates how studying a rare but important disorder, like Gaucher disease, can provide powerful clues about more common disorders, such as Parkinson's disease," said NHGRI Scientific Director Eric Green, M.D., Ph.D. "Understanding the genetic basis of rare conditions can thus provide insights into normal cellular and biological processes, which in turn may lead to improved diagnostic and therapeutic strategies.' "
Read the full article here: http://www.nih.gov/news/health/oct2009/nhgri-21.htm
Dr Sidransky is also interested in investigating the possible association between NPC and three specific neurodegenerative disorders - Parkinson disease, ALS (Lou Gehrig disease), and early-onset Alzheimer disease (diagnosed before the age of 65). The aim would be to see if a relative of an NPC patient who has any of these other neurodegenerative diseases also carries an NPC mutation. See also “Neurodegenerative Disease in Family Members of Patients with Niemann-Pick Disease, Type C” .
[Oct 30, 2009 mem]
"Compassionate" Access to Investigational Drugs
Single Patient Investigational New Drug Application or "Compassionate Use"
"Single patient Investigational New Drug (IND) application" refers to the treatment of a seriously ill patient using a new, unapproved drug when no other treatments are available. Drugs that are being scientifically tested but have not yet been approved by the United States Food and Drug Administration (FDA) are called investigational drugs. Being permitted to use one of these drugs outside of a clinical trial specifically designed to study that drug may be commonly referred to as "compassionate use."
"Compassionate use" is more properly termed "single patient Investigational New Drug (IND) application."
For more information, click here.
[Sept 30, 2010 mem]
Enzyme Replacement Therapy Clinical Trial (Type B)
Phase 1 Concluded
Results from Phase 1 of the Enzyme Replacement Therapy Clinical Trial (Type B) will be presented at the American Society of Human Genetics Meeting in October. Read the message from Dr. Margaret McGovern regarding the conclusion of Phase 1, and view the poster she and her team presented at the International Congress for Inborn Errors of Metabolism.
[Sept 14, 2009 mem]
Zavesca Officially Launched in United Kingdom
On July 21, 2009, Actelion Ltd. announced the launch of Zavesca® (miglustat) in the UK and Republic of Ireland; the first and only licensed treatment available for people with Niemann-Pick type C (NP-C) disease.
Ed Wraith, M.D., Royal Manchester Children's Hospital, commented: "For the first time we have an approved therapy for NP-C. The data on the effects of treatment with Zavesca® obtained in a clinical trial and in a retrospective cohort study consistently showed a favorable clinical response. As a treating physician I am acutely aware of the importance of reducing progression of neurological symptoms."
Zavesca®, which was granted orphan drug status allowing for a faster approval process, is now approved in all EU countries for the treatment of patients with NP-C and is available in all the EU countries according to the local reimbursement process. Regulatory proceedings to extend the use of Zavesca® in patients with NP-C are ongoing in other countries worldwide.
Click here to read the complete press release.
[Aug 19, 2009 mem]
Dr. Patterson's Grand Rounds Video from Seattle
Dr. Marc Patterson's Grand Rounds, given while in Seattle for the NNPDF's 2009 Family Support and Medical Conference, are available for viewing at the following link:
NPC Clinical Trial Opportunity
Message from Dr. Forbes "Denny" Porter, National Institutes of Health
The NNPDF has received an update from Dr. Denny Porter at the National Institutes of Health regarding an upcoming NPC Clinical Trial opportunity. Please click here to read Dr. Porter's message.
We encourage anyone with questions about the study to contact Nicole Yanjanin at Dr. Porter’s office: 1-301-594-1765; email@example.com.
Dr. Porter plans to present more details related to this trial at our upcoming NNPDF Family Support and Medical Conference in Seattle, Washington, July 30 - Aug. 2. Please contact the NNPDF Central Office if you need assistance registering or finalizing your travel plans for the NNPDF Family Conference.
[July 9, 2009 mem]
Updates on OrphaNews
Newsletter of the Rare Diseases Task Force
Visit OrphaNews Europe to read the following updates:
National and International Policy Developments: A Canadian province adopts rare disease drug evaluation programme.
Ethical, Legal and Social Issues: An international expert group reiterates the need to adhere to guidelines for stem cell clinical applications.
[July 13, 2009 mem]
Papers Published in Cell Metabolism Journal
Dr. Heiko Runz of the University Clinic - Heidelberg (Germany), has a paper titled "Identification of Cholesterol-Regulating Genes by Targeted RNAi Screening" published in the July 2009 issue of Cell Metabolism.
Read the announcement here: http://www.eurekalert.org/pub_releases/2009-07/embl-sic070609.php
The full text of the paper is available here: http://www.cell.com/cell-metabolism/fulltext/S1550-4131(09)00157-0
This research was funded in part by the Ara Parseghian Medical Research Foundation.
In the same issue of Cell Metabolism is an article by Drs. Munkacsi, Pentchev and Sturley:
[July 13, 2009 mem]
NIH Announces New Program to Develop Therapeutics for Rare and Neglected Diseases
The National Institutes of Health is launching the first integrated drug development pipeline to produce new treatments for rare and neglected diseases. The $24 million program jumpstarts a trans-NIH initiative called the Therapeutics for Rare and Neglected Diseases program, or TRND.
For more details, visit: http://www.nnpdf.org/NIHTherapeuticsforRareandNeglectedDiseases.html
[May 26, 2009 CWV]
NNPDF/Peter G. Pentchev
Request for Applications
In 2008 the NNPDF Board undertook an extensive review of its research funding strategy and produced a new Strategic Plan for Research.
As a result, we are pleased to announce that the NNPDF will fund Post Doctoral Research Fellowships in all areas of promise with regard to Niemann-Pick Disease.
The NNPDF Board is determined to ensure that research funds are well spent and to provide funding that is most likely to accelerate finding an effective therapy or cure for all types of Niemann-Pick Disease.
Please click here to learn more about NNPDF/Peter G. Pentchev Research Fellowships, or hover your mouse pointer/cursor over the Niemann-Pick Research tab in the bar above (in light blue box) to view a dropdown list of more Research pages.
[Feb 20, 2009 mem]
A Prospective, Cross-sectional Survey Study of the Natural History of Niemann-Pick Disease Type B
Chemical chaperone could open door to treatment of neurological disorder. (Posted February 6th, 2008.)
Year-1 results show that miglustat improves or stabilizes several clinically relevant markers of Niemann-Pick Type C.
Genzyme announces novel gene therapy approach for NPD Types A and B.
Graver WS, Francis GA, et al. 2007. Am J Med Genet A. 143A(11):1204-1211.
Miglustat (Zavesca) animal toxicology study data released
Sidman RL, Li J, Stewart GR, Clarke J, Yang W, Snyder EY, Shihabuddin LS. Brain Res. 2007 Apr 6;1140:195-204. Epub 2007 Jan 9. PMID: 17289003 [PubMed - in process]
Stem cell treatment of mouse model of NPD type A shows improvement in some areas.
Mihaylova V, Hantke J, Sinigerska I, Cherninkova S, Raicheva M, Bouwer S, Tincheva R, Khuyomdziev D, Bertranpetit J, Chandler D, Angelicheva D, Kremensky I, Seeman P, Tournev I, Kalaydjieva L. Brain. 2007 Mar 14; [Epub ahead of print]
Findings indicate that mutation analysis is of limited value in predicting brain damage in intermediate ASM deficient NPD (Type A/B variant), and the option of enzyme replacement therapy should be considered.
Floyd AG, Yu QP, Piboolnurak P, Wraith E, Patterson MC, Pullman SL. Clin Neurophysiol. 2007 Feb 26; [Epub ahead of print]
The first descriptive analysis of upper limb motor physiology in Niemann-Pick Type C disease. These quantitative methods may help to evaluate efficacy, and side effects, of new treatments as they are developed.
Imrie J, Dasgupta S, Besley GT, Harris C, Heptinstall L, Knight S, Vanier MT, Fensom AH, Ward C, Jacklin E, Whitehouse C, Wraith JE. J Inherit Metab Dis. 2007 Feb;30(1):51-9. Epub 2006 Dec 11. PMID: 17160617 [PubMed - indexed for MEDLINE]
The clinical presentation and follow-up of 94 patients with NPC is described, 58 of whom were still alive at the time this report was prepared. The age at diagnosis ranged from the prenatal period (with hydrops fetalis) up to 51 years.
larner B, Klunemann HH, Lurding R, Aslanidis C, Rupprecht R. J Inherit
Metab Dis. 2007 Feb;30(1):60-7. Epub 2006 Dec 11.
PMID: 17160616 [PubMed - indexed for MEDLINE]
Evaluation of a test battery that could be used to assess cognitive deficits in different stages of NPD Type C. Observations found that visuospatial working memory was less affected by the neurodegenerative process than verbal working memory.
Beltroy EP, Liu B, Dietschy JM, Turley SD. J Lipid Res. 2007
Jan 14; [Epub ahead of print]
PMID: 17220530 [PubMed - as supplied by publisher]
Studies used npc1-mutant mice to investigate the association between liver dysfunction and unesterified cholesterol accumulation. Results suggest it is the late endosomal/lysosomal content of unesterified cholesterol that correlates with cell damage in NPC disease.
Garver WS, Jelinek D, Oyarzo JN, Flynn J, Zuckerman M, Krishnan K, Chung BH, Heidenreich RA. J Cell Biochem. 2007 Jan 10; [Epub ahead of print] PMID: 17216601 [PubMed - as supplied by publisher]
Results from this study support the hypothesis that an accumulation of lipoprotein-derived cholesterol within late endosomes/lysosomes, in addition to altered intracellular cholesterol homeostasis, has a key role in the biochemical and cellular pathophysiology associated with NPC1 liver disease.
Kulinski A, Vance JE. J Biol Chem. 2007 Jan 19;282(3):1627-37. Epub 2006 Nov 15. PMID: 17107950 [PubMed - indexed for MEDLINE]
Investigation of liver disease in NPC1-deficient mice. Observations indicate that the enhanced secretion of lipoproteins from NPC1-deficient hepatocytes is due, at least in part, to increased lipid synthesis.
Linder MD, Uronen RL, Holtta-Vuori M, van der Sluijs P, Peranen J, Ikonen
E. PMID: 17050734 [PubMed - indexed for MEDLINE]
Mol Biol Cell. 2007 Jan;18(1):47-56. Epub 2006 Oct 18.
Results show that the overexpression of the recycling/exocytic Rab GTPase Rab8 rescued the late endosomal cholesterol deposition and sphingolipid mistrafficking in NPC fibroblasts. Rab8 is established as a key component of the regulatory machinery that leads to ABCA1-dependent removal of cholesterol from endocytic circuits.
Reddy JV, Ganley IG, Pfeffer SR. PLoS ONE. 2006 Dec 20;1:e19. PMID: 17183645 [PubMed - in process
NPC1 mutant cells display an inappropriate homeostatic response to accumulated intracellular cholesterol. In addition, a number of striking parallels were observed between NPC disease and Alzheimer's disease.