TESTING THE IN VIVO EFFICACY OF PTC680, A PROMISING TREATMENT FOR FAMILIAL DYSAUTONOMIA

Alyssa Bernstein, Eckerd College, Biology Discipline

Emily Kirchner1, Dadi Gao1, Ricardo Harripaul1, Anil Chekuri1, Elisabetta Morini1,  Susan Slaugenhaupt1

1Center for Genomic Medicine, Massachusetts General Hospital Research Institute

Familial dysautonomia (FD) is an autosomal recessive neuropathy specific to the Ashkenazi Jewish population that affects the development and survival of sensory and autonomic neurons. FD is caused by a splicing mutation in the Elongator acetyltransferase complex subunit 1 (ELP1), an important part of the elongator complex. Using a phenotypic FD mouse model, TgFD9/ELP1∆20/flox , the lab focused on testing the therapeutic efficacy of a splicing modulator compound, PTC680, to determine the effects on proprioceptive loss, particularly gait ataxia, neuronal abnormalities, and retinal degeneration, all of which are symptoms seen in patients with FD. Mice were genotyped using DNA extraction, PCR, and gel electrophoresis. As shown previously by the lab, PTC258, an analog to PTC680, rescues proprioceptive loss in the FD mouse, as seen via Catwalk software for gait analysis and immunohistochemical analysis in mouse dorsal root ganglion. Preliminary results show that PTC680 is a promising modulating compound that both rescues ELP1 splicing and improves gait function in the FD mouse model.

For more information, contact albernst@eckerd.edu.