HDAC Inhibition Therapy to Stop Neurodegeneration? Notre Dame and Cornell Scientists PNAS Paper To Show How Histone Deacetylase Inhibitor (HDIs) Corrects Niemann Pick Type C Cholesterol Defect

Notre Dame and Cornell researchers are reporting a major breakthrough in Niemann Pick Type C disease research that has major relevance to other progressive neurological conditions such as Alzheimer’s, Huntington’s, and ALS.

A paper coauthored by Olaf Wiest and Paul Helquist of the University of Notre Dame’s Department Chemistry & Biochemistry and Frederick Maxfield, Chair of Biochemistry at Cornell University Weill College of Medicine, is apparently going to appear in the Proceedings of the National Academy of Sciences this week according to a press release issued by Notre Dame.

The paper apparently shows how the use of a histone deacetylase inhibitor corrects the damage done in Niemann Pick Type C,  a fatal genetic cholesterol metabolism disorder, and allows once-diseased cells to function normally. The press release discusses the “effectiveness of the drug” but no compound is named.

Histone deacetylase inhibitors (HDIs) have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics.  In more recent times, HDIs are being studied as a treatment for neurodegenerative diseases so the fact these researchers are having such success in NPC cells is very promising.

Interestingly, our neurologist Dr. Daniel Birnbaum at Children’s Hosptial Research Center Oakland started Addi and Cassi on Valproic Acid, an anti-seizure medicine that is also classified as an HDAC inhibitor.  We have had good success with Valproic Acid over the past three months.

Trichostatin A, suberoylanilide hydroxamic acid (SAHA), Phenylbutyric Acid and Butyric Acid can all act as HDAC inhibitors as well.  Maybe it’s one of these compounds that is showing success in the Niemann Pick Type C cells?

The press release does not say whether testing was done in NPC mice or NPC cats or if the HDAC inhibitors worked in NPC animal models.  I hope the paper discusses animal work.  The good news is that many HDAC inhibitors are in advanced clinical trials or even approved drugs.  I hope these compounds can also easily cross the blood brain barrier!

HDAC inhibition therapy — is this the miracle we have all been waiting for?   I hope so and if  it is Notre Dame and Cornell researchers will be heros for their in work that will extend beyond NPC disease.

More information on Histone deacetylase is here.