Huntington’s disease treatment breakthrough

This debilitating neurodegenerative disease is currently incurable. But an exciting breakthrough treatment is offering patients hope.

Health Agenda magazine
July 2018.

Huntington’s disease is a serious and rare genetic brain disease. There’s currently no cure, but an experimental drug is showing promising results and giving those living with the disease, and their families, hope.

What is Huntington’s disease?

The disease is caused by a defective gene that produces too much of a protein called huntingtin. The build-up of this protein damages cells in the brain, affecting the nervous system.

If you have the faulty gene, it isn’t possible to prevent or slow the disease. It’s very rare to have the faulty gene if neither of your parents do.

The symptoms typically appear when people are in their 30s or 40s and worsen over time.

People with Huntington’s can have different symptoms but, in general, it can affect your ability to think, walk, speak and swallow. It can also cause involuntary movements and mental health problems. People with Huntington’s usually die around 15 to 20 years after their symptoms first appear, mostly due to complications such as pneumonia and heart failure.

Associate Professor Clement Loy, neurologist and director of the NSW Huntington Disease Service at Westmead Hospital, says cognitive (brain), behavioural and personality changes frequently occur before movement symptoms.

“For many people, it’s not until issues with movement occur that they get diagnosed with Huntington’s. This can be devastating for many families because they hadn’t realised the cognitive, emotional and behavioural changes have been part of the disease,” he says.

A person with Huntington’s may be diagnosed based on family history or genetic testing, in addition to an assessment of symptoms.

Current treatment

While there’s no cure for Huntington’s, there are medications that help control some symptoms. Some medications help suppress involuntary movements and some antipsychotic medications may assist in subduing the movements and help manage agitation and excessive mood swings.

“Most patients will take some medication in addition to participating in an exercise plan and receiving support from a treatment team including a neurologist, psychiatrist, nurse, social worker, physiotherapist, speech pathologist, occupational therapist and dietitian,” says Assoc Prof Loy.

A research breakthrough

In 2017, an Ionis Pharmaceuticals study showed that an experimental drug called RG6042 could lower the amount of the problematic protein ‘huntingtin’ (also known as mHTT) in the spinal fluid for people in the early stage of the disease.

“This protein causes the breakdown of nerve cells in the brain, believed to be the underlying cause of Huntington’s disease,” says Dr Scott Schobel, associate group medical director at Roche, the pharmaceutical company which is handling the next phase of research.

The data show that the largest reductions of mHTT were seen in participants who received the 2 highest doses of RG6042 for 3 months – of up to 60% in some cases. 

Dr Schobel says these findings are important because it’s the first time a therapy has been shown to reduce mHTT in people with Huntington’s. The trial only had 46 participants so a much larger trial will be necessary to demonstrate the drug’s efficacy and safety before it can become widely available.

“This study will determine whether the lowering of mHTT translates into meaningful benefit for people living with Huntington’s. We recognise the urgent need to bring effective therapies to individuals affected and are working to advance RG6042 into the next clinical study as quickly as possible,” he says.

Living with Huntington’s

David, 63, was diagnosed with Huntington’s 11 years ago. He finds the news of the treatment breakthrough exciting.

“I take an interest in research that’s going on,” he says, speaking slowly and pausing every 4 or so words. “I’m always very encouraged by the research that’s being done. I take big tablets every morning and at night and I wouldn’t have to take any pills if we could have this gene silencing.”

As an active person who loves the outdoors, David has been determined to maintain his physical capabilities for as long as possible.

“I used to go on lots of long bushwalks with friends of ours in places like the Blue Mountains and Snowy Mountains,” he says. “I’ve given those away but each weekend I go for a walk with what we call my 4-wheel-drive walker.”

David’s wife Christine says his exercise program is very important to him, as are the connections he has with others who have Huntington’s.

“David participates in a lunch club with Huntington’s NSW and is an important member of that social club,” she says. “He’s fairly motivated to get out and spend time with people and continue on with his exercises because he sees the benefit of doing so.”

David and Christine’s 2 adult children each have a 50% chance of having Huntington’s. David’s mother was diagnosed in her 60s. “She died when she was 82,” says David. “That’s a good innings for Huntington’s, but I’m going to beat her!”

Looking to the future

Assoc Prof Loy says he is “cautiously optimistic” about the future. 

“If [these gene-silencing agents] do work then, for the first time, we may be able to slow the disease or even stop it. I think it will take at least another 5 years before we know whether this approach will work. But out of the 100 or so trials that have been carried out in the past few decades, this recent one is the most exciting.

“I’m optimistic that something will work and will transform what we do and the lives of people with Huntington’s.”

Image credit: Christopher Ireland