TESTING THE IN VIVO EFFICACY OF PTC680 IN RESCUING RETINAL DEGENERATION IN A MOUSE MODEL OF FAMILIAL DYSAUTONOMIA

Abstract

Familial dysautonomia (FD) is an autosomal recessive hereditary neuropathy that affects the development and survival of sensory and autonomic neurons. FD is caused by a splicing mutation in intron 20 of the Elongator complex protein 1 (ELP1) gene that leads to tissue-specific skipping of exon 20, mainly when the gene is expressed in the central and peripheral nervous systems. In FD, visual impairment typically begins early in life and often progresses to legal blindness by the third decade. Individuals with FD show a significant reduction in the amount of retinal ganglion cells (RGCs). To determine the therapeutic efficacy of splicing modulator compound PTC680, RGC cells in the retina and full-length ELP1 transcript in retinal tissue were quantified using a phenotypic FD mouse model, TgFD9/ELP1∆20/flox. Our data provide strong evidence of improved RGC counts and correction of ELP1 mis-splicing in mouse retinal tissue following postnatal oral administration of PTC680.

For more information: amiura@eckerd.edu