Why you should care

Because scientists might have discovered a way to delay the onset of Huntington’s disease — and convince more at-risk individuals to enroll in clinical trials.

Throughout much of her teen years, Kristen Powers watched a neurodegenerative illness called Huntington’s disease (HD) gradually destroy her mother’s life. Declining motor skills meant her mother fell more often, bruising her skin and scraping her knees. She lashed out in violent outbursts. Later, she lost the ability to speak altogether, uttering only small noises. Eventually, she moved into a nursing home, where she died in 2011 at the age of 45.

Powers knew she had a 50 percent chance of inheriting the genetic disease that had killed her mother. And she knew that if she had HD, she risked passing it on to her future children. But the self-described “information-needy” teenager wanted to know for sure. So when she turned 18, she decided to undergo genetic testing to find out whether she had HD, too. In Twitch, a documentary Powers filmed to tell her story, she sat expressionless in an examining room in the children’s outpatient clinic at the University of North Carolina, bracing herself for the results.

“We have good news for you today,” the genetic counselor said. “You tested negative.” A smile instantly lit up Powers’ face, while her dad sobbed and hugged her.

The possibility of remaining blind to their HD status might make at-risk individuals more willing to enroll in clinical trials.

More than 250,000 Americans are at risk for developing HD and many grapple with the same decision: to test or not to test. Those who decide not to undergo testing still want to find treatments, since there’s no way to cure HD or slow its progression. The problem is that clinical trials seek certain numbers of HD-positive and -negative participants, meaning that prospective participants must provide genetic test results that confirm their disease status. But Massachusetts General Hospital researchers recently completed a trial cleverly designed to respects patients’ right not to know their genetic information — which also revealed that a nutritional supplement known as creatine might delay the onset of HD symptoms.

Woman on left with child on right outdoors sitting on steps

Author with her mother

Described in the journal Neurology last month, the new trial design could also give a needed boost to HD research: the possibility of remaining blind to their HD status might make at-risk individuals more willing to enroll in clinical trials.

Unlike other neurodegenerative disorders like Alzheimer’s disease, HD is caused by mutations in a single gene. Those who carry the mutations begin to show symptoms around age 40, starting with muscle twitches and progressing to loss of motor control and dementia.

A single defective gene causes HD, making diagnosis possible even before symptoms appear. This feature also makes this hereditary disease ideal for controlled scientific studies. But since enrolling in clinical trials requires them to confirm whether they have the disease, they often forgo them.

Individuals with Huntington’s disease progress from muscle twitches to loss of motor control and dementia.

But why not know your status? Some might cite the fear of losing their health insurance. After all, not too long ago, those with preexisting health conditions couldn’t readily get a health insurance policy. But even in the United Kingdom, which provides free health care to all permanent residents, “Only about one in four at risk come forward and get tested,” says H. Diana Rosas, a neurologist at Massachusetts General Hospital who led the new study. Often, however, more personal fears play a role.

“Genetic discrimination is a problem in trial design. We should be more creative and open-minded,” Rosas says. “Many carriers have to live with the fact they have exposed their families to the disease. Their caregivers and children see them becoming shadows and ghosts of their former selves, losing their personality, intellect and all the things that make you ‘you.’ These households know that this may be their fate and they don’t know when it is going to happen.” Plus, why know ahead of time whether you have a disease that has no cure?

Dr on left and patient on right of frame

Scene from the movie

Rosas’ clinical tral might offer a solution. The phase II trial enrolled 64 participants: 19 who knew they had a mutated HD gene, and 45 who had a 50 percent chance of carrying the disease but preferred not to know their status. Rather than requiring study participants to provide genetic test as proof of their HD status, the study staff tested the participants themselves. But the results were made available only to a statistician, not to the study staff or participants. Testing brought the total number of HD-positive patients to 26. Meanwhile, 17 HD-negative participants served as controls.

Participants were randomly assigned to two groups, regardless of their HD status. One group received an oral dose of creatine twice a day, while the other got a placebo. Six months later, all participants received creatine for an additional year.

Often found in energy bars and protein shakes, creatine works by restoring ATP, the molecule that powers most biological processes. But it does more than beef up bodybuilders and athletes; previous studies have shown that it holds promise for treating Parkinson’s disease, muscular dystrophy and other neurodegenerative diseases.

A high-dose creatine regimen had slowed the rate of degradation in brain regions known to be affected by the disease.

Rosas’ team took MRI scans of the participants’ brains at the trial’s outset, after six months and then after the trial had ended. The MRI images were stunning — revealing that a high-dose creatine regimen had slowed the rate of degradation in brain regions known to be affected by the disease.

Fifteen participants stopped taking creatine because they couldn’t stand the taste or the stress of being reminded of their HD risk, for example. But the drug had few adverse effects, other than occasional diarrhea and nausea.

Today, Xenazine is currently the only FDA-approved drug that alleviates involuntary movements, a primary feature of HD. But Xenazine increases risk of suicidality in HD patients, causing a need for alternative treatments of HD-associated symptoms.

Creatine is now being tested on larger groups of participants in a phase III trial, expected to wrap up in three years. Findings from this trial could reveal biomarkers — such as the presence of certain proteins — that could indicate the severity of HD. These can then be used to assess the therapeutic benefit of creatine and other experimental treatments. The current study is also designed to assess creatine’s ability to treat other diseases, such as Alzheimer’s.

“I want to make this the last generation with Huntington’s disease,” Powers says in the trailer for her documentary. Creatine might at least buy this generation some time, already a big step. And Rosas’ innovative trial design could be applied to future experimental drugs, possibly bringing Powers’ bold declaration within reach.

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