Diseases of the eye are often the indication of choice for new, advanced forms of medicine, particularly gene therapies. Delivery to the eye is straightforward and proven, effective doses can be very low, and the structures of the interior of the eye are relatively isolated from the rest of the body. All told, the risk to patients is much lower than would be the case for targeting, say, the liver, which makes it a great deal easier to convince investors and regulators to support such a program. Thus we shouldn't be all that surprised to see that the first clinical trial of partial reprogramming to rejuvenate epigenetic control over nuclear DNA structure and gene expression will focus on regeneration of the damaged retina.
The FDA has given the go-ahead for the first ever human trial of a partial epigenetic reprogramming therapy. The FDA's decision clears an investigational new drug application for Life Bioscience's ER-100, a gene therapy designed to rejuvenate damaged retinal cells in people with serious, age-related eye diseases. The biotech is now preparing to commence a Phase 1 first-in-human study to show its therapy can be delivered safely in patients with open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy (NAION).
As a first-in-human trial, Life Bioscience's study is primarily focused on safety and tolerability. Instead of using all four Yamanaka factors, ER-100 employs three of the factors (Oct4, Sox2, and Klf4) delivered transiently to reset age-associated epigenetic markers while keeping cells committed to their original function. By excluding c-Myc, a factor associated with uncontrolled growth, the strategy is intended to lower the risk of tumors that has historically concerned regulators and clinicians. From a safety perspective, the company's preclinical studies in non-human primates demonstrated that ER-100 was well tolerated in NHPs, with no systemic toxicities.
"The therapy uses a doxycycline-inducible system, giving us precise control over when the genes are active and allowing treatment to be paused or stopped if needed. In addition, ER-100 is delivered locally to the eye, limiting systemic exposure. Multiple preclinical animal models have demonstrated controlled gene expression, favorable biodistribution, restoration of epigenetic markers, and improvements in visual function which has collectively provided the foundation for FDA clearance."
Link: https://longevity.technology/news/fda-clears-first-human-trial-of-epigenetic-reprogramming-therapy/
View the full article at FightAging
