Leber's Congenital Amaurosis results in photoreceptor death and significant visual loss in childhood. via

If you know someone affected by the blinding genetic condition, Leber's Congenital Amaurosis (LCA), then the recent studies on gene therapies have been giving us a reason to hope.  LCA is a rare genetic condition that results in significant vision loss during childhood due to death of the photoreceptor rods and cones that detect and process light information.  There are several genetic variants of the disease, and one (LCA2) has been isolated to a mutation in the RPE65 gene.  Isolating a disease to one gene mutation makes for an exciting option: the ability to replace that gene into the body with gene therapy!

The RPE65 gene codes for a protein essential in the way the retinal pigment epithelium supports the photoreceptor rods and cones and uses vitamin A to detect light.  When the mutation was identified, LCA2 became a prime target for genetic therapy treatment because it required just one snippet of code to be replaced.  Scientists can use virus vectors to insert the correct RPE65 gene directly into the eye (via intravitreal injection), with the hopes that the treated person will begin making the corrected protein, and regain that lost visual function.  Some of the first studies from the University of Pennsylvania and University of Florida were published in 2009 and showed improvement in visual function.

Now a few years into these studies, new reports are coming in.  Gene replacement treatment in these patients has been safe, but it appears that the retinal photoreceptors have continued to degenerate despite the gene therapy.  OCT scans show retinal thinning occurring at the same rate in both treated and untreated eyes even years after original therapy.  It appears that gene therapy can improve vision for a period of time (how many years, we do not know), but the photoreceptors may still lose function long term.  Childhood treatment can help improve visual function but may not be enough to erase the damage during that early development. Early intervention appears to be key, but in humans LCA destruction is beginning even during development of the ocular tissue in the womb, so our capabilities for delivering this early treatment are limited.

Right now there are several Phase 3 clinical trials being run to assess long term benefit of RPE65 gene replacement therapy in LCA2, and the results look promising that vision can be improved at least temporarily.  To this point the published results have not shown any study participants suffering from vision loss, despite the progression to their retinal thinning, so it is too early to tell how long their visual improvements from gene therapy will last.  Trying to find a way to treat patients with gene therapy before they suffer retinal photoreceptor damage may be difficult, so scientists are looking at somehow combining gene therapy with other therapeutic treatment that may help stabilize retinal photoreceptor cells.  As of right now, no such medical treatment exists but eyes are on the use of LINGO-1 as a possible neuro-regenerator.  The science is new and innovative and sure to meet many hurdles along the way, but we are living in an exciting world of possibilities!