13.06.2024

Developments in gene therapies and legal access to innovative treatment

Gene therapy is a therapeutic method that uses genes and the information they carry to treat a genetic disease or modify cellular behavior. Some of the gene therapies have proven effective in improving disease, but they come with a high price tag and other affordability issues: even when people know a protocol exists for their disease, and even if they can afford it or have an insurance company that will cover the cost - which can range from $400,000 to $2 million - they may not be able to travel to the few academic centers that offer it. Other therapies relieve symptoms but do not eliminate the underlying cause.

Thanks to this new knowledge and constant investigation, gene therapy researchers can now point to a growing list of successful gene therapies.

There are, unfortunately, cases of babies born with severe vision loss caused by retinal diseases that once inevitably led to total blindness. Today, some of them may benefit from a gene therapy created by husband-and-wife research team Jean Bennett and Albert Maguire, who are now ophthalmologists at the University of Pennsylvania.

When the pair began researching retinal disease in 1991, none of the genes now known to cause vision loss and blindness had been identified. In 1993, researchers identified a potential target gene, RPE65, and seven years later tested a therapy targeting that gene in three dogs with severe vision loss, with dramatic results - restoring sight to all three.

In humans, the inherited condition that best corresponds to vision loss in dogs is Leber congenital amaurosis. This prevents the retina, a layer of light-sensitive cells at the back of the eye, from reacting correctly or sending signals to the brain when a photon hits it. The condition can cause uncontrolled shaking of the eye (nystagmus), prevents the pupils from responding to light and usually leads to total blindness by the age of 40. Researchers have linked the disease to mutations or gaps in any of 27 genes associated with retinal development and function. Until gene therapy, there was no cure.

Mutations in RPE65 are only one of the causes of inherited retinal dystrophy, but it was a cause that researchers were able to act on. The researchers used a harmless adeno-associated virus, which they programmed to find retinal cells and insert a healthy version of the gene, and injected it into a patient's eye directly under the retina. In 2017, after a series of clinical trials, the Food and Drug Administration approved the drug, marketed as Luxturna, for the treatment of any inherited retinal dystrophy caused by the mutant RPE65 gene, including congenital amaurosis type 2 and retinitis pigmentosa, another congenital eye disease that affects photoreceptors in the retina. Luxturna was the first FDA-approved in vivo gene therapy that is delivered to target cells inside the body (previously approved ex vivo therapies deliver the genetic material to target cells in samples collected from the body, which are then reinjected).

Beyond the scientific success itself, there are many legal questions. For example, given the extremely high costs of these treatments, who will be entitled to benefit from them? Naturally, there will always be people who can afford the very high medical costs. Usually, however, because life is ironic, they are not the people who need those expensive treatments.

Ethical considerations aside, public health systems can only operate within a pre-determined budget, where demand always exceeds supply. As more and more innovative treatments will be offered by genetics, obviously at substantial cost, legislation will have to meet patients with a set of transparent procedures that will carry out what in fact no one is directly responsible for, namely sorting out who can and who will not benefit from these treatments.

For the time being, both in Romania and in other countries, the choice is left to the health and insurance systems. Recourse to the judicial system is sporadic and the outcome usually late and unpredictable.

An article by Veronica Dobozi (vdobozi@stoica-asociatii.ro), Partner, STOICA & ASOCIAȚII.