A paper announcing a breakthrough discovery in the fight against Niemann-Pick Type C, coauthored by and of the University of 91³Ō¹Ļās and Frederick Maxfield, Chair of Biochemistry at Cornell University Weill College of Medicine, appears in the Proceedings of the National Academy of Science this week. The paper shows how use of a histone deacetylase inhibitor corrects the damage done by the genetic disorder and allowed once-diseased cells to function normally.
(NPC) involves a genetic flaw that keeps cells from using lipids appropriately and leaves the lipids trapped in the cell. Brain cells are especially impacted, and destruction of brain cells typically kills victims by their teen years. There currently is no treatment available in the U.S. NPC is an inherited cholesterol metabolism disorder that strikes one in every 150,000 children. It has been referred to by the National Institutes of Health as āchildhood Alzheimerāsā because of similarities in the brains of NPC and Alzheimerās disease patients.
Three of the four grandchildren of former 91³Ō¹Ļ head football coach Ara Parseghian died of NPC, and the University has been involved in research on the disorder for years. Last year, it with the , which sponsored this work.
Last summer, 91³Ō¹Ļ College of Science Dean Gregory Crawford and his wife Renate from Tucson to 91³Ō¹Ļ to raise awareness of the newly strengthened partnership with the Parseghian Foundation. 91³Ō¹Ļās works to develop therapies and outreach efforts for people suffering from conditions, like NPC, that have been largely ignored by pharmaceutical companies.
A team of researchers led by Wiest and Helquist at 91³Ō¹Ļ and Maxfield at Cornell, uncovered evidence that histone deacetylase inhibitors correct NPCās genetic flaw. Detailed images obtained at Cornell by Maxfieldās group gave vivid evidence of the drugās effectiveness, showing how NPC cells became indistinguishable from normal human cells after treatment with the drug. The histine deacetylase inhibitors have a wide range of potential uses, from rare diseases, the focus at 91³Ō¹Ļ, to several forms of cancer, including leukemia, where they can increase the number of bone marrow cells.
Several of the compounds studied are shown to be safe in advanced clinical studies of cancer and one compound currently is approved by the FDA.
āOur biggest single emphasis the last few years has been Niemann-Pick among these rare diseases,ā Helquist said. āWe developed several processes for the efficient preparation of these types of drugs. Thereās a stream of publications and also a stream of patents starting in June 2007 and continuing this year.ā
āIf the results in human cells can be confirmed in clinical trials, the fact that the histone deacetylase inhibitors are already in advanced clinical trials or even approved drugs could greatly accelerate the development of a treatment for this devastating disease.ā
Contacts: Olaf Wiest, owiest@nd.edu and Paul Helquist, phelquis@nd.ed, 91³Ō¹Ļ; Frederick Maxfield, frmaxfie@cornell.edu, Cornell.
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