With the first gene therapy for blindness in the market, the door has been opened for a new wave of gene therapy treatments with the potential to cure genetic blindness.
In December 2017, the FDA approved Luxturna, the first ever gene therapy to treat a genetic disease causing blindness. A year later, the therapy was approved in Europe with the help of Novartis.
Developed by Spark Therapeutics, Luxturna is designed to fix mutations in a gene called RPE65 that cause blindness. A single injection in each eye has shown to be enough to improve vision for at least 3 years.
Although its price has caused controversy, Luxturna has set a precedent for many other gene therapies in development that are aimed at fixing the many different genetic mutations that can result in blindness. Interestingly, France seems to be the hub where most of these efforts are taking place.
How gene therapy for blindness works
Gene therapy provides 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 for infection while allowing the translation of the DNA it carries into a functional protein.
Gene therapy is particularly suited to treat the eye. 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 for delivery. In addition, the cells of the retina can keep this DNA functioning for longer than other cells in the body.
“These cells don’t renew or mutate, and therefore should conserve DNA expression 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.”
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 is GenSight. This Parisian company aims to restore sight in patients with Leber hereditary optic neuropathy, a rare disease that causes irreversible vision loss.
GenSight suffered an unexpected setback during clinical trials, where patients treated with the therapy in just one eye saw improvements in the eye that had been treated with placebo. But the company sees it as an advantage and is now seeking approval for the therapy in Europe and the US.
Biogen recently acquired Nightstar Therapeutics, a London-based company working on gene therapies for blindness. With the acquisition, Biogen has incorporated to its pipeline a treatment for choroideremia, a condition that impairs night vision. Being tested in phase III trials, the gene therapy is the most advanced for this condition — Luxturna’s developer is also targeting choroideremia, but its therapy is still in early clinical trials.
Back to Paris, the company Horama is seeking to cure retinitis pigmentosa, a hereditary disease that results in progressive vision loss. The company recently 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 inserts 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?
Although the progress made by gene therapy is astounding, one of its limitations 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 expensive, making it unfeasible to develop one for each mutation, especially for extremely rare mutations. To overcome this challenge, some companies are designing new approaches to make a single therapy suitable for everyone.
That is the goal of GenSight. The company is developing a treatment that combines gene therapy with a wearable device to potentially treat all types of retinitis pigmentosa. As CEO Bernard Gilly explained, 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 I/II trial with this technology has started in the UK.
Sounds great, but how much will it cost?
Gene therapy is unfortunately not cheap. In the US, Luxturna costs a whopping $425,000. Per eye. That makes Luxturna one of the most expensive drugs in the world (along with other gene therapies such as Novartis’ Zolgensma or bluebird bio’s Zynteglo).
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).
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. One of the most anticipated 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 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.