Innovative Approach Targets Mitochondrial Dysfunction to Protect Children’s Vision

Autosomal dominant optic atrophy (ADOA) is the most prevalent inherited optic nerve disorder, often beginning subtly during childhood with symptoms like blurred vision, difficulty focusing, or mild vision test failures. Despite its gradual onset, ADOA can lead to progressive, irreversible vision loss due to the degeneration of retinal ganglion cells (RGCs), which are essential for transmitting visual information to the brain. This damage is primarily linked to mutations in the OPA1 gene that disrupt mitochondrial function—cells’ energy producers and health regulators.

Recent groundbreaking research by scientists at Boston Children's Hospital, led by Thomas Schwarz, Ph.D., and Chen Ding, Ph.D., has uncovered a promising therapeutic target aimed at preventing RGC damage. The discovery was partly motivated by a family in 2019 that requested research help for their daughter at risk of ADOA, prompting scientists to explore if their studies on mitochondrial dysfunction could help preserve her vision.

The team's latest study, published in the Journal of Clinical Investigation, revealed that disabling a protein called SARM1 could protect RGCs and sustain vision. SARM1 is known to initiate axon degeneration—the process that causes nerve fibers to break down—which is central to the progression of ADOA. In experiments with mouse models carrying the OPA1 mutation, removing SARM1 kept RGCs healthy and maintained their visual function. This insight offers a new perspective in neurodegenerative disease treatment—aiming not just to slow damage but to intervene at a molecular level to halt it altogether.

Building upon these findings, the Schwarz Lab is now examining whether pharmaceuticals can inhibit SARM1 activity, paving the way for potential therapies. One promising candidate is ASHA-624, a drug designed to keep SARM1 inactive, thereby preventing nerve degeneration.

As SARM1-targeted therapies move closer to clinical trials, early diagnosis through genetic screening becomes crucial. Identifying at-risk children promptly can provide opportunities for future interventions, offering hope for preservation of vision rather than inevitable loss. This innovative approach signifies a major shift in treating ADOA, moving towards molecularly targeted treatments that could be within reach soon.