Gene Therapy Slows Huntington’s by 75% in ‘Groundbreaking’ Clinical Trial

Doctors in the UK are claiming to have performed a monumental medical breakthrough. Using a form of gene therapy, they successfully treated—for the first time—the neurodegenerative disorder Huntington’s disease.

On Wednesday, the company uniQure announced the results of its phase I/II trial testing the therapy, code-named AMT-130. The trial, conducted with the help of researchers from University College London, found that AMT-130 slowed the progression of people’s symptoms by 75%. It also appeared to reduce the death of brain cells, a signature feature of the disease. It’s still early days, but the results could soon herald the arrival of a remarkable treatment for the currently life-shortening condition.

“I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington’s disease, where an urgent need persists,” said Sarah Tabrizi, director of the UCL Huntington’s Disease Center and the study’s lead scientific advisor, in a statement from UCL.

A genetic curse

The disease is triggered by a mutation in the huntingtin gene, which causes the body to produce a defective version of the huntingtin protein. This mutant protein then gradually destroys brain cells, particularly those found in the areas that govern movement and cognition. The genetic mutation that causes Huntington’s is dominant, meaning people only need to have one copy of it from a parent for the disease to occur; as such, a person has a 50% chance of inheriting it if one of their parents carries the mutation.

People typically live into their 30s and 40s before symptoms appear, such as trouble moving. But the disease progressively worsens from there, and people will eventually develop dementia and other serious health problems. Most people with Huntington’s only live 15 to 20 years once the illness manifests. And though there are treatments that can help people manage their symptoms, there is no therapy that will stave off its inevitable destruction of the brain—until now, quite possibly.

Short-circuiting Huntington’s

AMT-130 is intended to short-circuit the process by which Huntington’s slowly kills off the brain.

Using a neutered virus to deliver DNA to a person’s brain cells, the therapy instructs these cells to produce a small bit of genetic material called microRNA. This microRNA should then hamper the cells’ ability to produce huntingtin protein (both the normal and mutant versions), in turn hopefully reducing the damage caused by the disease. And since brain cells aren’t constantly recycled like other parts of the body, the gene therapy ideally only needs to be a one-time treatment.

The primary part of the trial involved 29 patients with early Huntington’s who were treated with AMT-130 (some patients in the control group would later receive treatment as well). At 36 months, the treatment met its main goal, appearing to slow people’s symptoms by 75%, as judged by a common scale used to assess the illness. Biomarker tests also suggested the treatment prevented further expected brain cell death. What’s more, the results were most impressive in people given the highest dose, indicating a true therapeutic response (the dose-response effect).

Though none of the patients are being identified, some are still walking despite being expected to require a wheelchair by this point, the BBC reported Wednesday, while one person has returned to work after initially taking a medical retirement. While it’s still too early to know for sure, it’s possible the level of improvement seen with AMT-130 could provide years, even decades, of extended life and good health to patients.

The therapy also appeared to be safe and tolerable, with most adverse events linked to the general anesthesia and surgery needed to deliver the therapy to the brain.

The future of AMT-130

Importantly, the company’s data has yet to be reviewed and evaluated by outside researchers, an important part of the scientific process. So these results remain preliminary for the time being.

But the company is certainly banking on its data to stand up to scrutiny. It plans to meet with the Food and Drug Administration later this year, and assuming all goes well, will formally submit an application for the therapy’s approval early next year.

Even if this therapy is approved, however, there will be important questions about how accessible and affordable it will be for the people who need it. Gene therapies are generally very expensive, and AMT-130 is unlikely to be an exception. But for the first time ever, patients with this incurable condition may have real hope.