Optic neuritis oral drug candidate presented at North American Neuro-Ophthalmology Society meeting

Cambridge, MA-Oral drug candidate SRT501 (Sirtris Pharmaceuticals) when administered suppresses neurological dysfunction in a preclinical model of multiple sclerosis, according to researchers. The data will be presented at the North American Neuro-Ophthalmology Society annual meeting by Kenneth Shindler, MD, PhD, assistant professor of ophthalmology at the University of Pennsylvania Scheie Eye Institute and lead investigator.

Earlier work in the same preclinical models shows that the activation of the SIRT1 enzyme with SRT501 is neuroprotective for optic neuritis because it reduces the loss of retinal ganglion cells. Mirroring the effects on the central nervous system observed in patients with multiple sclerosis, Dr. Shindler's team in the new work used mice with experimental autoimmune encephalomyelitis (EAE).

Signs of EAE were observed in mice, measured by strength and duration of tail and limb paralysis. Daily oral doses of SRT501 at 1,000 mg/kg were given to mice starting at day 10 through day 14, the peak day of autoimmune system attack. Paralysis scores of the treated mice improved more completely than those of untreated mice following the first clinical episode of EAE.

"We have previously established that we can reduce the loss of retinal ganglion cells during acute optic neuritis in mice with EAE by using SRT501 when injected into the vitreous layer of the eye," said Dr. Shindler. "This work shows oral SRT501 exerts similar effects in optic neuritis and leads to suppression of observed dysfunction in the first clinical episode of EAE, suggesting added neuroprotective benefits of SIRT1 activation."