Breakthrough at Notre Dame

Artical from the Wall Street Journal
By Amy Dockser Marcus

Researchers at Weill Cornell Medical College and the University of Notre Dame said they used drugs being tested for cancer to correct a cholesterol-storage defect in a lethal, rare disease called Niemann-Pick Type C (NPC).

The researchers found that a compound called LBH589, part of a group of drugs called histone deacetylase (HDAC) inhibitors, corrected the defect in human NPC cells in a lab setting. The LBH589 compound is being studied in clinical trials to treat several forms of cancer, including brain cancer. The idea of repurposing drugs used in more common diseases to try to treat rare conditions is an increasingly popular approach to drug development.

The finding, published this week in the Proceedings of the National Academy of Science, is considered early stage since the experiments were done in tissue culture models of NPC, a genetic cholesterol-metabolism disorder that is ultimately fatal. Typically, promising compounds are then tested in an animal model before being tried in humans. Compounds that work in cells are not always effective in animals or humans.

Paul Helquist, one of the authors of the PNAS paper and a professor of chemistry and biochemistry at Notre Dame, says the researchers are hopeful that the class of inhibitors might be useful not only in NPC disease but in other neurodegenerative disorders where lipids inappropriately accumulate in cells. He said that they would like to test the compound in a cat model of NPC disease.

The paper comes at a time when the NIH is gearing up for a clinical trial involving another promising compound, cyclodextrin, that has been tested in animal models and is being given experimentally to a small number of children. Last week, NIH director Francis Collins discussed the NIH’s NPC efforts in a webinar sponsored by the FasterCures organization.

It isn’t easy to get clinical trials going in rare diseases like NPC, which affects only an estimated 500 people world-wide. The number of patients is so small that it is difficult to attract pharmaceutical company interest. As a result, unusual partnerships are sometimes needed between patient advocacy organizations and researchers to try to drive research and trials.

The PNAS paper represents one such partnership. The research was funded in part by the Ara Parseghian Medical Research Foundation. Parseghian, the former Notre Dame head football coach, had three grandchildren who died from NPC.

Last summer, the Notre Dame College of Science dean and his wife biked over 2000 miles from Tucson — where the Parseghian Foundation is based — to Notre Dame to raise awareness about NPC. The foundation set up an endowment at Notre Dame last year to support research into and an annual scientific conference about the disease.

Among the programs, Notre Dame offers an undergraduate course at its Center for Rare and Neglected Diseases to teach undergraduates how to collect and analyze data from NPC patients. Notre Dame also has a program open to researchers who want to synthesize potential drugs for use in experiments or trials in rare or neglected diseases, including NPC.

Photo: Associated Press