The NNPDF does a wonderful job of keeping families and people interested up to date on how things are progressing in the disease community for Niemann-Pick Type C. You can visit updates on their page here: http://www.nnpdf.org/aboutus_14.html

Cyclodextrin

A few families have taken a different approach in individually seeking the approval of the FDA to start an individual trial. Some of their hard work contributed in helping promote the upcoming Cyclodextrin trial.  Cyclodextrin could be one of many therapies needed in the future to help NPC patients manage the disease progression.

Letter From TRND

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

Press Release:

NIH Therapeutics for Rare and Neglected Diseases Program announces next round of drug development projects

Related posts:

1. Potential Breahthrough in Niemann-Pick Type C Research
2. Orphan Drug Designation for Cyclodextrin | NPC

Niemann-Pick Type C is essentially a generic flaw keeping lipids trapped in the cell and prevents cells from using the lipids appropriately. The destruction of brian cells, which is the most crucial area, typically kills the affected individuals by their teenage years. NPC strikes approximately one in every 150,000 births. NPC is a genetic inherited neurological disorder that involves the lack of cholesterol metabolism within the cells.

A recent claim published by Olaf Wiest and Paul Helquist of the Univeristy of Norte Damn and Frederick Maxfield of Cornell University says that a histone deacetylase inhibitor (HDAC) corrects the damage done by NPC and allows the previous diseased cells to function normally.

This obviously would appear like wonderful news except we have to remember not to jump to premature conclusions drawn from this press release. This whole disease and finding a suitable treatment is so complicated. There have been many times in the past that something in the lab has shown to cure NPC but only to later show that it wasn’t feasible in actual humans or animal studies.

One of the leading Niemann-Pick Type C experts 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, urged caution on 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.

If there was ever a time to have a child or loved one with Niemann-Pick Type C, it would be in our current timeline. Research is making head way but that head way has to be weighed by the fact that in research time it might be moving fast but to parents that timeline will never be fast enough to help their dying children now.

To view more detailed information about this press release and feedback: http://www.nnpdf.org/npdisease_14.html#ValproicAcid

Photo used under Creative Commons from jepoirrier.

Related posts:

1. New therapies – Niemann-Pick type C disease
2. Promising Therapies for Niemann-Pick Type C Disease
3. Video: What is Niemann-Pick Type C disease? Can you share?

In Rockville, MD on June 3-4th many of the researchers looking into different areas and avenues for Niemann-Pick Type C came together to discuss promising therapies. Although research is making progress, parents of NPC patients never feel that research is happening fast enough. That is greatly to be expected. The NPC community is  making large strides in the right direction!

The National Niemann Pick Disease Foundation was very kind in putting together a recap of that meeting in a pdf format which is viewable here: Promising Therapies for Niemann-Pick Type C Disease.

Related posts:

1. New therapies – Niemann-Pick type C disease
2. What is Niemann-Pick Type C?
3. Canada Receives First Approved Treatment For Niemann-Pick Type C