1800 244 735

Helpline (02) 9874 9777

Anti-nausea drug helps cells with the HD mutation stay healthy in a surprising way

The connection between cellular energy levels and HD is more complicated than we previously thought, but in a way that opens a door to more possible treatments. It seems drugs that actually slow down the production of energy can rescue cells with the HD mutation from dysfunction and death.

Energy in HD

Energy is a big problem in HD. One of the most common symptoms in people with HD is weight loss: the emaciated facial features of HD patients are immediately recognizable to many HD family members. Surprisingly, not much is known about how and why this happens. HD patients generally eat as much as people without HD, if not more, but they have a hard time keeping on weight. So it seems that the problem is not getting enough calories, but some problem with using the energy they consume.

Scientists are beginning to understand that one of the jobs of the huntingtin protein is to regulate energy production within cells. Dr Marcy MacDonald’s group of researchers have shown that in blood cells from HD patients, longer CAG repeats in the huntingtin gene go along with lower total energy levels. That’s important, because longer CAG repeat counts tend to produce an earlier age of onset of the disease.

Because of that link between CAG repeats and energy, researchers have been looking at whether bolstering energy levels might be helpful in HD. Several trials underway, including those with creatine and coenzyme Q10, are based on the idea that increasing energy levels in HD will be helpful.

But symptoms in HD are complex – it can be difficult to figure out which symptoms are causing the disease, and which symptoms are the body’s attempts to deal with it. It’s a bit like having a fever – it’s not comfortable, but it’s one way the body fights infections. So, are reduced energy levels in HD causing the disease, or something the body is doing to cope with another problem we don’t understand?

Could reducing metabolism be good for cells with the HD mutation?

A surprise came about two years ago, when a team of researchers working with Dr Brent Stockwell at Columbia university were looking for drugs that rescue cells with the HD mutation from dying. They found that drugs that slow down metabolism, or energy production, made cells with the HD mutation healthier.

That caused some confusion – energy levels are low in cells with the HD mutation, and many HD patients take drugs aimed at increasing their energy levels. Despite this, Stockwell’s team suggested that or slowing down metabolism can protect cells with the HD mutation. Could this be true?

Vamsi Mootha, working with Vishal Gohil and others, has been working to understand the situation. Energy levels are also important in conditions like heart attack and stroke, where important cells are not getting enough oxygen. Previously, Mootha has shown that a compound called meclizine protects heart cells from damage caused by lack of oxygen.

Meclizine works, in part, a bit like the way Stockwell’s compounds worked, so he tested it in another HD cell model. Meclizine does turn out to protect cells with the HD mutation from dying, and it does so by slowing down their metabolism, in agreement with Stockwell’s data.

It’s not clear if the effects observed by Stockwell and Mootha will translate from cells to HD patients. In order to improve on simple cell models, Mootha examined the effects of Meclizine in worm and fly models of HD. These animal models showed some improvements when treated with Meclizine, but additional studies in mice or rats would be beneficial. Rodent studies take more resources and time to conduct, which is why scientists often study shorter-lived organisms like flies and worms first.

Now what?

This set of unexpected findings demonstrates why we have to be very careful with drug development in HD. On the surface, it’s easy to look at a problem like low energy levels and conclude that increasing energy levels would help. But, if we dig below the surface, the picture becomes more complex. It’s still not clear what aspect of metabolism is damaging cells with the HD mutation, or how it’s helped by Meclizine, but you can be sure that these scientists are trying to figure it out.

An interesting twist to the story is that Meclizine is already an approved drug – but not for HD. It’s an anti-nausea drug that’s available over the counter in many countries. It’s too early for anyone to take any drug based on this research, but it’s heartening to see that researchers are trying to use drugs in their scientific studies that could quickly translate to use in humans, once we understand them better.

Share on facebook
Share on twitter
Share on pinterest
Share on email

Latest Research Articles

Scientists identify precisely how pridopidine works in models of Huntington’s disease

Published date: 12 June, 2021

Pridopidine is a drug developed to treat Huntington’s disease (HD) and now scientists have a clearer understanding of how it works in the body and brain. In a series of academic papers, researchers figured out that pridopidine is working by targeting a particular receptor protein called S1R. With this new understanding, the researchers believe pridopidine ... Read more

Huntington's disease therapeutics conference 2021 – Day 3

Published date: 29 April, 2021

We are back for the last day of the virtual 2021 CHDI Therapeutics conference. This article summarises our live Twitter updates on the exciting science being presented, which you can find with the hashtag #HDTC2021. The final session of the conference will provide the latest news on more Huntington’s disease clinical programs. A new way ... Read more

Huntington's disease therapeutics conference 2021 – Day 2

Published date: 28 April, 2021

We are back with Day 2 of the virtual 2021 CHDI Therapeutics conference. This article summarises our live Twitter updates on the exciting science being presented, which you can continue to follow with the hashtag #HDTC2021. The morning session focussed on promising HD therapeutics that are in preclinical development and the afternoon session covered different ... Read more

Huntington’s disease therapeutics conference 2021 – Day 1

Published date: 28 April, 2021

The CHDI Therapeutics Conference 2021 kicked off today. This article summarizes our live Twitter updates on the exciting science being presented, which you can continue to follow with the hashtag #HDTC2021. The morning of Day 1 focused on clinical trial updates, while the afternoon explored genetic modifiers of HD and how they might be harnessed ... Read more

Huntington’s disease clinical trial round up

Published date: 26 April, 2021

It seems like the HD community has been inundated with updates from different companies and clinical trials recently. The news is far from complete doom and gloom; although there have been some real disappointments from some of the frontrunner trials, there are also positive updates from many different companies and lots of reasons for us ... Read more

Good news from uniQure: gene therapy trial on track, and promising data in animals

Published date: 15 April, 2021

Two recent press releases from uniQure provide welcome good news: the first ever HD gene therapy, known as AMT-130, has been administered via brain surgery to a small set of participants in an early safety trial. At the same time, uniQure has published findings in HD animal models that increase confidence in the drug’s ability ... Read more