Rare Disease Day takes place annually on the last day of February. Rare Disease Day’s goal is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients. Warren Center researchers have a rich history in rare disease therapeutic research and a few examples are summarized below.
Niemann-Pick type C disease is a rare lysosomal storage that affects young children and is typically fatal. A team of researchers led by Professors Olaf Wiest and Paul Helquist for Notre Dame’s Department of Chemistry & Biochemistry, and Fred Maxfield at Cornell Weill Medical College, uncovered evidence that histone deacetylase inhibitors (HDACi) have the ability to improve cholesterol trafficking in NPC-mutant cells. This collaborative effort continued to progress and HDACi are now the subject of a proof of concept clinical trial. More recently, Warren Center Interim-Director Rich Taylor (Department of Chemistry & Biochemistry) and collaborators in the San Francisco-based Perlstein Lab, PBC, have identified a unique set of compounds that are capable of restoring cholesterol trafficking in NPC mutant fibroblasts at low nanomolar concentrations significant below that observed with HDAC inhibitors. These results may have also identified a novel mode of action for the treatment of NPC as well as other genetic diseases. NPC research at Notre Dame and the HDACi clinical trial are being supported by Notre Dame College of Science, the Ara Parseghian Medical Research Foundation, and the National Institutes of Health.
Due to the Center’s previous experience leading rare disease collaborations, the Grace Science Foundation connected Warren researchers with Retrophin, Inc. and established a collaboration focused on identifying a treatment for NGLY1 deficiency, a rare genetic disorder. The condition is characterized by a variety of symptoms, including global developmental delay, movement disorder, seizures, and ocular abnormalities. Enabling this effort, the Grace Wilsey Foundation has provided support to Retrophin to enable collaborative discovery efforts, with researchers in the Warren Center, that aim to validate and address a new molecular target that may be relevant to NGLY1 deficiency. Professors Richard Taylor, Bruce Melancon, Tony Serianni, along Helquist and Wiest are leading this effort with the Center.
In another example, Professor of Biological Sciences, Shaun Lee, has been working to develop a computational algorithm to access genetic mutations and cellular models for a high-throughput assay for MPS IIIA, Sanfilippo Syndrome A, a specific type of rare mucopolysaccharidosis involving aberrant metabolism of heparan sulfate (HS). People inflicted with MPSIIIA accumulate complex carbohydrates in their cells and tissues, especially in brain. If untreated, individuals inflicted with this lysosomal storage disorder typically die before 15 years of age. Unfortunately, there is no currently effective treatment for MPS IIIA. The project is a collaboration with Professor Serianni, a structural glycobiologist with expertise in the synthesis, purification and characterization of saccharide-based agents that may have potential therapeutic activity against MPSIIIA disease.
Learn more about Rare Disease Day and rare diseases at http://www.rarediseaseday.org/