Wonderful news: uniQure’s one-and-done drug slows Huntington’s disease

 

AMT-130, a one-time gene therapy developed by uniQure, has successfully slowed the progression of Huntington’s disease.

 

While that is not a cure, and the therapeutic process is hardly simple, it is the first evidence that scientific progress translates into meaningful results for those suffering from HD.

 

The treatment is far more complex than a pill: it involves 12 to 18 hours of delicate brain surgery. A neurosurgeon injects AMT-130 directly into the brain under the guidance of an MRI. As a gene therapy, AMT-130 requires just this one application. (Watch the uniQure video about how AMT-130 is administered here).

 

According to clinical trial results reported by uniQure on September 24, AMT-130 achieved its main goal (primary endpoint) and demonstrated a 75 percent slowing in the progression of the disease over a three-year period.

 

“High-dose AMT-130 also demonstrated statistically significant slowing of disease progression as measured by TFC, a key secondary endpoint, and favorable trends across additional clinical measures,” the release stated. TFC is total functional capacity. It refers to a person’s ability to function – a key loss in HD.

 

Other progress

 

The company, based in Lexington, MA, and Amsterdam, reported that AMT-130 also reduced the measure of a protein known as neurofilament light, a marker of disease that reveals stress on the brain.

 

The clinical trial showed “favorable trends” in other second measures of motor (movement) and cognitive function, the release stated. Movement disorders and cognitive loss are major HD symptoms. Trial results demonstrated that AMT-130 is safe and well-tolerated.

 

“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,” Sarah Tabrizi, M.D., Ph.D., a leading HD specialist at University College London, stated in the release. “These data indicate that AMT-130 has the potential to meaningfully slow disease progression – offering long-awaited hope to individuals and families impacted by this devastating disease.”

 

 

David Margolin, M.D., Ph.D., uniQure's vice president for clinical development, presents data illustrating ATM-130's slowing of the progression in Huntington's disease at the 20th Annual HD Therapeutics Conference, Palm Springs, CA, February 25, 2025 (photo by Gene Veritas, aka Kenneth P. Serbin).

 

Transforming the HD landscape

 

AMT-130 seeks to lower the amount of harmful mutant huntingtin protein in the brain cells of patients. Whether the drug has actually done this has yet to be verified.

 

In early 2026, uniQure plans to apply to the U.S. Food and Drug Administration (FDA) for drug approval. Pending drug approval, the drug would be launched in the U.S. later in 2026.

 

“We are incredibly excited about these topline results and what they may represent for individuals and families affected by Huntington’s disease,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders.”

 

Hopes for a life-long treatment

 

“This is the first time any drug has been shown to alter the course of HD in people in a clinical trial,” the scientist-written website HDBuzz stated. “uniQure believes that AMT-130 has the potential to be a treatment that lasts for life.”

 

uniQure officials told HDBuzz that, beyond the FDA, they plan to seek approval with other regulators, including the European Medicines Agency, which oversee drug approvals in Europe.

 

HDBuzz cautioned that key details need to be worked out before AMT-130 can be administered to a large group of people beyond the fewer than 30 people whose data were analyzed by uniQure.

 

Only some of those individuals received the high dose of the drug that proved effective. Also, because AMT-130 requires an operation, the company must find a way to provide access to the drug, and at an affordable level, to a larger number of people.

 

On the whole, despite the caveats and complexities, this is wonderful news for the HD community.

 

"We never in our wildest dreams would have expected a 75% slowing of clinical progression," Dr. Tabrizi told the BBC.

As a ‘biological being,’ I embrace science’s fight against disease

 

I am a biological being.

 

This phrase came to me about a decade ago, and I have been hoping to write about its meaning for a long time.

 

Now, with scientific research at key American institutions such as the National Institutes of Health and university labs under attack from the Trump administration, the phrase resonates with me stronger than ever.

 

From the time I was hospitalized in 1977 with two herniated discs after shoveling heavy snow through decades of participation in Huntington’s disease research studies, I have been acutely aware of my body as the object of biomedical observation.

 

Seeing scans of deteriorating HD brains at scientific conferences leaves me deeply worried about the shrinking of my own brain – the inevitable result of the fact that I carry the HD gene.

 

In March 2022 I observed preliminary data presented by Triplet Therapeutics from SHIELD-HD, a two-year research study of 70 presymptomatic and early-disease-stage carriers of the HD mutation. Triplet aimed to use SHIELD-HD to support plans for a groundbreaking clinical trial to attack a key driver of HD, somatic expansion, the mutant huntingtin gene’s tendency for continued expansion with age. The program was scuttled because the firm folded in October 2022 as it lacked investment funds.

 

The 2022 SHIELD-HD data showed deterioration in the brains of the gene carriers.

 

For the first time, I saw information about the impact of the HD gene on my own brain. I had volunteered for SHIELD-HD, undergoing MRI brain scans and cognitive tests and giving samples of blood and my cerebrospinal fluid (CSF) at the HD clinic at the University of California, San Diego.

 

Below are photos of me in the clinic in August 2022, just two months before the Triplet shutdown. The first shows a neurologist injecting an anesthetic to prepare for the drawing of my CSF. In the second photo the doctor draws a small amount of my CSF. It was the last of my several CSF drawings over the course of SHIELD-HD. Scientists see analysis of CSF, which bathes the brain, as a major tool in the search for therapies for HD. 

 

Having CSF drawn is a safe procedure but can be painful. Each time I drove home by myself within a couple hours of the drawing. I am very glad I did it.

 

 

 

 

Analysis of SHIELD-HD

 

With the end of Triplet, final analysis of the key SHIELD-HD data was completed by CHDI Foundation, Inc., the largest private funder of HD research. The analysis was presented at the 19th Annual HD Therapeutics Conference, sponsored by CHDI, in February 2024.

 

A future article will further explore my participation in SHIELD-HD and the importance of that program for HD research.

 

The 20th Therapeutics Conference: a sign of collaboration

 

As a biological being, I embrace science, not useless conspiracy theories. At the University of San Diego, where I teach and research, I began a new course this month called “A History of the Brain: Examining Huntington’s Disease.” One key lesson from the history of brain science: reliance on superstition was replaced with scientific observation – the key to solving neurodegenerative disorders like HD.

 

On a large scale, so has the HD community participated in and supported science – from the start of the hunt for the gene in the 1970s to programs today such as Enroll-HD. Tens of thousands of individuals from around the world have taken part, despite the fact that HD is a rare disease, with about 40,000 affected individuals in the U.S.

 

CHDI, the Huntington’s Disease Society of America, the Hereditary Disease Foundation, Help4HD International, and other HD organizations also rely on science and cooperate with scientific institutions.

 

A magnificent example of scientific collaboration will take place starting this evening in Palm Springs, CA, as the 20th HD Therapeutics Conference gets under way at the Parker hotel.

 

Stay tuned for reports about the meeting.