Brutal, so far intractable disease may finally have a treatment

Doctors in the United Kingdom are reporting that they’ve successfully used gene therapy to treat Huntington’s disease for the first time. With the treatment, the doctors said it would take four years to see the level of decline typically seen in a single year.

Professor Sarah Tabrizi told BBC News it offers patients a “good quality life.”

The genetic disease has been likened to a combination of Alzheimer’s disease, Parkinson’s and multiple sclerosis at the same time for the havoc it wreaks for those who inherit the condition, though there are varying degrees. It kills both brain cells and motor skills and within a couple of decades, the individual dies.

Approximately 75,000 people in the U.S., European Union and UK have Huntington’s, while hundreds of thousands of their offspring have the potential to inherit it. No cure or even tool to slow progression has been found.

In 1999, Deseret News followed four generations of a Utah family that had multiple members living with the condition and others waiting to see if they would inherit the autosomal dominant disorder, which gave each individual a 50% chance of developing Huntington’s. In many families, the disease shows up after an individual already had one or more children.

As the BBC reported, since first symptoms typically appear in one’s 30s or 40s, the researchers believe that earlier treatment could prevent symptoms from emerging at all, since the disease can be discovered through genetic testing.

The treatment is given in a 12- to 18-hour brain surgery and they acknowledge it will likely be expensive. So is caring for someone who has the disease.

While the team didn’t divulge who the patients receiving treatment in a clinical trial were, they did say that one had taken a medical retirement and has since returned to work. They said some patients are walking, though without treatment they would likely be using a wheelchair.

A brutal disease

As Deseret News earlier reported in an article called “Generations of Tears,” the disease is marked by progressive degeneration from within the brain. Symptom severity hinges on how many brain cells are lost.

“Most cruel of all, doctors say that people with Huntington’s retain their memories of who and what they were before. But it destroys the ability to reason, to communicate, to focus,” the article reported.

Huntington’s was first documented in 1872 and bears the name of the doctor who discovered the symptoms, Dr. George Huntington. He said that similar descriptions could be traced as far back as the Middle Ages.

He discovered, correctly, that if someone didn’t inherit the disease, they could not pass it on. So whole branches of families are sometimes at risk, while others are not.

The gene therapy

The mutation causing Huntington’s is in the huntingtin protein, which leads to toxic proteins in the brain cells. The gene therapy uses a virus that has a specific DNA sequence. It’s placed deep in the brain by way of a microcatheter, using a functional, real-time MRI to reach the caudate nucleus and the putamen. The virus delivers the DNA inside brain cells and they create their own therapy.

As BBC explained it, the cells produce a small fragment of genetic material called microRNA that intercepts the messenger RNA instructions for building mutant huntingtin, leading to less of the mutated protein in the brain.

The gene therapy company uniQure issued a press release Wednesday announcing the results from the phase I/II clinical study, and heralding “significant slowing of disease progression.”

The study involved 29 patients, some treated with high dose and some treated with low dose of the therapy, called AMT-130.

Said Tabrizi in the release, “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. 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.”

uniQure said that the high dose group saw “consistently favorable results in functional, motor and cognitive endpoints at 36 months,” while the low dose group results varied. That suggests a “dose-dependent response to AMT-130. It also noted that the gene therapy was generally well tolerated and the safety profile was manageable at both doses.

It’s a small study in early phase trials, however, and more research is needed. It could be several years before the treatment is widely available, assuming it continues to prove effective. But those paying attention are already discussing the potential to treat other neurodegenerative disorders as well.