Overview of Interests
Dr. Niswender is the Director of Molecular Pharmacology for the Vanderbilt Center for Neuroscience Drug Discovery and is involved in many aspects of the drug development process, with a focus on drug development for neurological and psychiatric disorders, particularly schizophrenia, Parkinson's disease, Fragile X syndrome and Rett syndrome. With seed funding from a Basic Research Grant from the International Rett Syndrome Foundation, Dr. Niswender and associates have found that metabotropic glutamate receptor 7 (mGlu7) is a direct MeCP2 target that is downregulated in a mouse model of Rett syndrome. They have found that small molecules that increase mGlu7 function can correct deficits in synaptic transmission in Rett syndrome model mice and plan to optimize additional small molecules to enhance mGlu7 activity as a therapeutic strategy for Rett. Dr. Niswender and her team have expanded these studies to include another glutamate receptor, mGlu5,and they have shown that compounds that increase the activity of mGlu5 have a dramatic effect on some of the motor aspects of Rett, such as hindlimb clasping and gait dynamics, in MeCP2 mutant mice. These data have paved the way for an Autism Speaks Treatment award, which will continue to support the group in their efforts to validate new drug targets in Rett syndrome and possibly other Autism Spectrum Disorders. As the VCNDD is currently developing mGlu receptor modulators in conjunction with pharmaceutical companies and the NIH, it is anticipated that their Rett work may be readily translatable to the clinic.
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