From Darkness to Light: Gene Therapy Breakthrough Offers Hope for Inherited Eye Diseases

Ten years ago, my mom shared a heartbreaking story that stuck with me.

It was about her friend's daughter, around my age, who lost her sight at a very young age due to a genetic condition called Retinitis Pigmentosa (RP).

Back then, the future seemed bleak for RP patients. But today, thanks to incredible scientific progress, a new ray of hope has emerged – gene therapy.

What is Gene Therapy?

Gene therapy is a cutting-edge approach that delivers healthy genes directly into cells to fix genetic defects that cause diseases. For inherited eye disorders like RP, this means replacing the faulty genes responsible for vision loss with functional ones.

A Groundbreaking Milestone

Gene therapy for eye diseases. (Image created using Canva)

In 2017, the FDA approved Luxturna, a gene therapy developed by Spark Therapeutics, to treat a specific form of retinitis pigmentosa (RP) caused by mutations in the RPE65 gene.

The treatment uses an adeno-associated virus (AAV) vector, to deliver functional copies of the RPE65 gene to retinal cells. The AAV vector is engineered to be non-pathogenic. The modified AAV vector is injected under the retina in a surgical procedure.

This revolutionary treatment has shown remarkable improvements in vision and light sensitivity for patients with the specific RPE65 mutation, as measured by their ability to navigate a mobility course at various light levels.

Luxturna was the first-ever gene therapy approved for an inherited genetic eye disease, paving the way for more breakthroughs.

Beyond Luxturna: A Spark of Hope from Ongoing Trials

While Luxturna marked a groundbreaking first, the fight against inherited eye diseases doesn't stop there. A new wave of clinical trials is exploring the vast potential of gene therapy for various retinal conditions:

• Ocugen's OCU400: OCU400 aims to improve retinal health and function by utilizing modifier gene therapy. Instead of targeting single gene mutation, OCU400 will address underlying cellular processes disrupted in various forms of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA), and even those caused by different gene mutations. Imagine a future where a single treatment could offer hope to a broader range of patients with these inherited retinal diseases.

• Editas Medicine's CRISPR Gene Editing: Heralding a new era of precision medicine, CRISPR technology is being used to directly edit the faulty genes responsible for LCA10 and Usher syndrome type 2A. This holds promise for a potential cure, offering a chance to rewrite the genetic code and restore vision.

• Beacon Therapeutics (formerly AGTC) AGTC-501: This therapy aims at X-linked retinitis pigmentosa (XLRP). AGTC-501 works by introducing a functional copy of the mutated gene, potentially restoring its role in healthy vision.

• REGENXBIO's ABBV-RGX-314: Developed in collaboration with AbbVie, the ABBV-RGX-314 gene therapy targets wet age-related macular degeneration (AMD), a condition affecting millions. 
  

• Other Notable trials: 4D Molecular Therapeutics' 4D-150 as a potential treatment for diabetic macular edema (DME) and wet-AMD. 
  

A Brighter Future

These ongoing trials represent a significant leap forward in the fight against inherited eye diseases. The results hold the potential to pave the way for new treatments, offering hope and a brighter future for millions living with vision loss.

This is not just a scientific breakthrough; it's a human story of resilience and the relentless pursuit of a cure. The journey from a personal encounter with RP to witnessing the dawn of gene therapy is a testament to the power of scientific progress and the unwavering hope for a world where vision loss is no longer an inevitable consequence of genetic inheritance.

As we eagerly await the outcomes of these trials, one thing is clear: gene therapy is shining a light on the path to overcoming inherited eye diseases, illuminating a future where sight is no longer a privilege, but a right for all.

Source:

• Banfi, S., & Berger, W. (2020). Gene therapy for inherited retinal diseases. Retinal Diseases Clinical Research, 2(1), 70–84. [PMC article]

• Food and Drug Administration (FDA). (2017, December 18). FDA approves novel gene therapy to treat patients with rare form of inherited vision loss. [Press release]

• Ocugen, Inc. (2023, June 14). Ocugen announces OCU400 modifier gene therapy Phase 1/2a data to be presented at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting. [Press release]

• National Eye Institute (NEI). (2020, March 12). Participants in pioneering CRISPR gene editing trial see vision improve. [Press release]

• Beacon Therapeutics Inc. (2023, April 12). Beacon Therapeutics announces positive 12-month data from Phase 2 SKYLINE trial of AGTC-501 in patients with X-linked retinitis pigmentosa. [Press release]

• REGENXBIO Inc. (2023, April 19). REGENXBIO announces Lancet publication of Phase II/III study results demonstrating durable safety and efficacy of RGX-314 for the treatment of wet age-related macular degeneration (AMD). [Press release]

• 4D Molecular Therapeutics. (2023, September 7). 4D Molecular Therapeutics Announces First Patient Enrolled in 4D-150 Phase 2 SPECTRA Clinical Trial in DME, and Expansion of 4D-150 Phase 2 Stage in PRISM Clinical Trial in Wet AMD. [Press release]. Assessed and Endorsed by the MedReport Medical Review Board