Last year ended on a high note for those suffering from a range of genetic disorders. In December, scientists based at St Bartholomew’s, London who had been investigating the genetic blood disorder haemophilia A came up with a new way to use a virus to carry the gene for a critical blood-clotting chemical to patients’ livers. According to the World Federation of Haemophilia, this development signals a potential cure for a condition affecting nearly half a million people globally.

In a remarkable breakthrough for Huntington’s disease patients, a team from University College London discovered a way to suppress the build-up of harmful proteins via injections of the drug Ionis-HTTRx. The ability to ‘silence’ the mutated gene offers hope for those not only with Huntington’s, but also with other neural conditions like Alzheimer’s.

These were only two of the latest medical advances in gene therapy that took place over the past year, with major breakthroughs for conditions like sickle cell disease, blindness, and spinal muscular atrophy (SMA).

Correcting the underlying causes of disease through modifications to patients’ DNA, rather than merely treating symptoms, signals a sea change in medicine and gives doctors the chance to administer a ‘one-shot’ cure. But hope of eradicating a range of debilitating conditions comes at a cost – up to $1 million per treatment – which has caused some lawmakers to reject new treatments for coverage, preventing some of their constituents from gaining access to new therapies. The question for patients thus becomes: how will public health regulators respond to new medical advancements?

The slow road to success

Twenty-five years ago, molecular biologists were just beginning to finetune the tools that would allow them to manipulate DNA. At the time, it was believed that gene therapy could address countless conditions, from Alzheimer’s to cancer. Yet with results slow to emerge, early optimism appeared to have been misplaced and, far from being an instant cure-all, gene therapy proved to be tricky to deliver.

It takes time to understand the pathway that leads to the onset of a disease and to isolate the stage at which it is most susceptible to modification. But now, the dedication of gene therapy specialists is beginning to pay off, with the recent announcement of a number of promising new treatments. According to the Alliance for Cell and Gene Therapy, 504 gene-therapy clinical trials are under way worldwide, including 34 in the most advanced stages of testing, with large pharmaceutical companies taking a keen interest in the sector.

What a difference a year makes

Over the past 12 months, in addition to the December breakthroughs, there have been exciting gene therapy developments for those suffering from genetic abnormalities, certain forms of cancer, and inherited blindness. In March, researchers announced the successful treatment of a young French patient with an experimental gene therapy designed to tackle sickle cell disease, an inherited blood disorder that affects millions.

Later in the year, the US Food and Drug Administration (FDA) approved two pioneering treatments, Kymriah and Yescarta, which use a patient’s own genetically modified T cells to fight rare types of cancer like lymphoma. A number of patients have responded positively and remain in remission months or years later.

Another promising treatment for retinal diseases that lead to blindness – Luxturna – has also been approved by the FDA. Though not an outright cure, the treatment, which was given the green light in October, has already restored vision for a number of patients who were losing their sight.

Hope – for some

New gene therapy treatment Spinraza has been one of the biggest recent developments. Spinraza (nusinersen) is the only known treatment for SMA, a rare disease that affects muscle strength and movement. It is caused by a deficiency in survival motor neuron protein which causes muscles to atrophy over time, complicating even basic motor functions like breathing. Infants stricken with the most severe form of SMA rarely live beyond age two.

In June, the European Medicines Agency (EMA) approved Spinraza for marketing authorisation in the EU. But many member states are still deciding whether or not to approve the drug for reimbursement, which is the only way patients can get affordable access.

Sweden has agreed to offer Spinraza to children suffering from SMA Type 1, and Italy has said it will offer the treatment for SMA sufferers irrespective of age, functional level, or type diagnosis. Other EU member states, such as Spain, France and the UK are in the process of deciding whether to approve Spinraza for coverage. In Denmark and Norway, however, the authorities have delayed approving the drug for patient reimbursement, concerning patients who need immediate access to the breakthrough treatment.

Luck of the draw

This conundrum exposes the extent to which public health policies still have to catch up with the times. As last year’s developments showed, breakthrough gene therapy treatments are being issued more rapidly than ever before, yet even governments in some of the wealthiest parts of the world – like Scandinavia – still balk at the price.

This, despite the fact that these treatments differ from other medicines in important ways. For one thing, in contrast with drugs that need to be purchased indefinitely, gene therapies are generally administered only for a truncated time period or even once, often with permanent effects. Mark Trusheim, director of MIT’s New Drug Development Paradigms program, has compared it to a shift from “renting” treatments to “buying” long-term improvements or even cures.

The price some of these treatments – Luxturna costs $425,000 (£300,000) per eye – might shock, but the overall impact on public insurers is relatively small both due to the one-off cost and the low incidence of these diseases.

When it comes to bringing a cure to patients, the discovery of a new treatment is merely the first step. The most difficult part is set to roll out over the coming months – meaning that for those suffering from haemophilia, Huntington’s, SMA, and other genetic diseases, it might be too soon to celebrate.


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Caroline Holmund

Caroline Holmund is a consultant and aspiring freelance journalist based in New York

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