Nav: Home

Stanford study identifies new biomarkers for Huntington's disease

November 07, 2016

Researchers at Stanford University School of Medicine have identified several new biological markers to measure the progression of the inherited neurodegenerative disorder Huntington's disease (HD). Their findings, which will be published online November 7 ahead of issue in The Journal of Experimental Medicine, could benefit clinical trials that test new treatments for the disease.

In HD, an expansion of a trinucleotide repeat sequence in the gene encoding huntingtin protein results in the production of a mutant form of huntingtin that can aggregate and damage cells, particularly neurons in the striatum and cerebral cortex. Patients display a progressive loss of voluntary and involuntary movements, as well as psychiatric and cognitive disturbances, and usually die 10-15 years after its onset.

Though genetic testing can identify HD patients long before their first symptoms appear in middle age, there are still no pharmacological treatments that can prevent or ameliorate the disease. A few drugs have shown promise in cell culture or animal models, but clinical trials in humans are time consuming because of the slow onset and progression of the disorder's clinical symptoms. Moreover, researchers are unable to take biopsies of the brain to assess the effects of potential therapeutic compounds.

One of the earliest events in HD is that mutant huntingtin aggregates disrupt the function of mitochondria, lowering cellular energy levels and causing oxidative damage. Daria Mochly-Rosen and her team at Stanford have previously identified a molecule, P110, that can restore mitochondrial function and prevent neuronal death in mouse models of HD (*). Now the researchers set out to identify markers of HD in non-neural tissues that could be used to track the progression of the disease and its response to P110 or other candidate drugs.

The team found that the levels of mitochondrial DNA, presumably released from dying neurons, were increased in the blood plasma of mice that were starting to develop the symptoms of HD. In contrast, mitochondrial DNA levels decreased at later stages of the disease. P110 treatment corrected plasma mitochondrial DNA back to the levels seen in healthy mice.

Mochly-Rosen and colleagues identified several other potential biomarkers that were elevated in HD model mice, including the levels of 8-hydroxy-deoxy-guanosine, a product of oxidative DNA damage, in the urine and the presence of mutant huntingtin aggregates and oxidative damage in muscle and skin cells. The levels of each of these biomarkers were reduced by P110 treatment.

It remains to be seen whether all of these biomarkers are reliable indicators of HD in humans. The Stanford team found, however, that mitochondrial DNA levels were significantly elevated in plasma samples from a small number of HD patients. "We have identified several biomarkers that correlate with disease progression and treatment in mice," says Mochly-Rosen. "We hope that our work will provide the basis for a larger study of patient samples that may ultimately identify biomarkers that can be used as surrogate markers to determine the benefit of therapeutic interventions in diagnosed but asymptomatic HD patients to prevent or delay disease onset."
-end-
(*) Conflict of interest statement: Several authors on this study own shares or share options in MitoConix, a company founded by Daria Mochly-Rosen that owns a patent on the design and application of P110.

Disatnik, M.-H., et al. 2016. J. Exp. Med.http://dx.doi.org/10.1084/jem.20160776

About The Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM provides free online access to many article types from the date of publication and to all archival content. Established in 1896, JEM is published by The Rockefeller University Press. For more information, visit jem.org.

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JEM on Twitter at @JExpMed and @RockUPress.

Rockefeller University Press

Related Clinical Trials Articles:

Review evaluates how AI could boost the success of clinical trials
In a review publishing July 17, 2019 in the journal Trends in Pharmacological Sciences, researchers examined how artificial intelligence (AI) could affect drug development in the coming decade.
Kidney patients are neglected in clinical trials
The exclusion of patients with kidney diseases from clinical trials remains an unsolved problem that hinders optimal care of these patients.
Clinical trials beginning for possible preeclampsia treatment
For over 20 years, a team of researchers at Lund University has worked on developing a drug against preeclampsia -- a serious disorder which annually affects around 9 million pregnant women worldwide and is one of the main causes of death in both mothers and unborn babies.
Underenrollment in clinical trials: Patients not the problem
The authors of the study published this month in the Journal of Clinical Oncology investigated why many cancer clinical trials fail to enroll enough patients.
When designing clinical trials for huntington's disease, first ask the experts
Progress in understanding the genetic mutation responsible for Huntington's disease (HD) and at least some molecular underpinnings of the disease has resulted in a new era of clinical testing of potential treatments.
More Clinical Trials News and Clinical Trials Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...