The first approval of a gene therapy for blindness in December has opened the way for a new wave of gene therapy treatments to cure genetic blindness. Let’s have a look at the different therapies promising to restore sight and their real potential. 

A few days before Christmas last year, the FDA approved the first gene therapy to ever treat a genetic disease causing blindness. Developed by Spark Therapeutics, Luxturna is designed to fix mutations in a gene called RPE65 that causes blindness. A single injection in each eye has shown to be enough to improve the lost vision for at least 3 years.

Novartis is now working to bring Luxturna in Europe, where multiple companies are developing their own gene therapy technology to address different mutations and diseases causing blindness. Interestingly, France seems to be the hub where most of these efforts are taking place. Let’s explore their technology and what they are up to.

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How gene therapy for blindness works

A gene therapy works by providing a functional copy of a gene that is missing or mutated. In the case of Luxturna, a copy of the RPE65 gene is delivered to the patient’s eye using a viral vector. The virus is modified to eliminate its capacity of infection while keeping the DNA sequences that lets the body read and translate the DNA into a functional protein.

Gene therapy is particularly suited to treat blindness and other eye diseases. First of all, the eye is an immune privileged area of the body where the immune system cannot detect and react against the viral DNA used as a delivery vector. Second, the cells of the retina that detect light do not get renewed as we age.

“These cells don’t renew or mutate, and therefore should conserve expressions all their lifetime,” says Bernard Gilly, CEO of GenSight. “A study on neurons in monkeys showed up to eight years of expression of the protein.”

gensight gene therapy blindness ophtalmology

Treating different forms of blindness

Following Luxturna, many biotech companies are advancing their own technology to fix different mutations causing blindness. One of the most advanced so far was GenSight, a Parisian company aiming to restore sight in patients with Leber hereditary optic neuropathy (LHON), a rare mitochondrial disease that causes irreversible loss of vision.

Although GenSight’s gene therapy did improve the sight of the patients significantly in one of their eyes, recent Phase 3 results showed that so did the placebo injected into the other eye. The company is now trying to figure out whether the therapy is affecting both eyes or it just is no better than a placebo.

While GenSight figures it out, another company from London is getting closer to launching a gene therapy for choroideremia, another rare disorder that causes blindness. Nightstar has just started a Phase 3 trial testing a gene therapy aiming to replace a missing protein necessary to remove waste from retinal cells to keep them healthy. Although Spark — Luxturna’s developer — is also working in choroideremia, it is still is early clinical trials.

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Back to Paris, the company Horama is seeking to cure retinitis pigmentosa, a hereditary disease that results in progressive vision loss. The company has just started a first trial in humans with a gene therapy that targets one of the most common mutations causing retinitis pigmentosa.

Another Parisian biotech called Eyevensys is seeking to remove the use of viruses in gene therapy for the eye. Eyevensys electroporates the DNA directly into the ciliary muscle — a tiny muscle that surrounds the iris and adjusts the focus. This can be done through a minimally-invasive procedure that lasts less than 2 minutes, according to the company.

Is gene therapy for everybody?

The progress made by more traditional gene therapy approaches is astounding, but one of the limitations of gene therapy is that each treatment can only fix a single gene. That significantly reduces the number of people that can benefit from a gene therapy when considering diseases like retinitis pigmentosa, which can be caused by mutations in 60 different genes.

Developing a gene therapy is extremely expensive, so developing 60 doesn’t seem feasible considering many of these mutations can be extremely rare. So instead, some companies are designing new approaches to make a single therapy suitable for everyone.

That is the goal of GenSight, which is developing a treatment that combines gene therapy with a wearable device to potentially treat all types of retinitis pigmentosa. As CEO Bernard Gilly explains, the gene therapy is used to introduce a light-sensitive protein within neurons in the optic nerve. A pair of goggles then “helps redirect and concentrate the light toward the modified cells, which will then convert it into a signal for the brain.” A Phase 1/2 trial with this technology is starting in the UK.

Sounds great, but how much will it cost?

Gene therapy is unfortunately not cheap. Luxturna costs a whopping $425,000. Per eye. Meaning that, after the withdrawal of Glybera — another gene therapy — last year, Luxturna is now the most expensive drug in the world.

We can expect upcoming gene therapies to have similar price ranges, especially for those treating rarer forms of genetic blindness. These prohibitive figures might mean that not everyone will have access to curative treatments.

One of the solutions some companies are testing include spacing out the payment over time and conditioning the payment to the therapy working. For example, Spark Therapeutics has set up a payment scheme for Luxturna in the US that is based on the outcome of the gene therapy. The company will offer partial refunds depending on whether the therapy works in the short term (30-90 days) or the long term (30 months).

This little green-capped vial of Luxturna (voretigene neparvovec-rzyl) comes with an $850,000 price tag per patient

The future is now

In the coming years, we can expect more and more examples of gene therapy for blindness to enter the market and start providing curative solutions for many patients in need. As technology advances, new technologies that make it work better, be safer and cost less will surely arrive. One of the most expected technologies is CRISPR-Cas9, a tool that has revolutionized the world by making gene editing much simpler than ever.

With CRISPR, it would be possible, in theory, to fix the mutation causing blindness directly in our cells. Although the technology is still in the early stages and the first treatments are directed at other conditions, US-based Editas Medicine is working with Allergan to develop a CRISPR therapy for blindness caused by Leber congenital amaurosis.

Still, the use of gene therapy will likely be limited to a small number of patients with specific mutations and rare diseases. It will take a long time before gene therapy can become a mainstream treatment that can really cure multiple causes of blindness.

However, as time goes on, advances in the technology will help expand the conditions in which gene therapy can cure blindness. And as technology advances and gene therapy is used more and more, the manufacturing process will become more efficient, reducing the costs of producing a gene therapy and therefore making it accessible to more people.


Images via GenSight; Eyevensys

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