Mass General researchers like Ghazaleh Sadri-Vakili, PhD, are pursuing new genetic advances that offer hope for Huntington’s disease treatments.

Ghazaleh Sadri-Vakili, PhD, director of the NeuroEpigenetics Laboratory at Massachusetts General Hospital’s Institute for Neurodegenerative Diseases (MIND), is uncovering important new clues that may lead to new treatments for Huntington’s disease (HD).

Medications can manage the symptoms, but no effective treatments have been developed to slow or prevent the disease.

Understanding why the disease progresses and how to stop it has been a research challenge. HD, which affects 1 in every 10,000 Americans, is an inherited disease that causes the progressive breakdown in nerve cells in the brain, resulting in psychiatric and neurological difficulties, including abnormal movements and cognitive impairments, as well as severe weight loss. Medications can manage the symptoms, but no effective treatments have been developed to slow or prevent the disease.

Dr. Sadri-Vakili’s lab studies gene expression; that is, the way instructions in our DNA are turned into functional products, like proteins or other molecules.

Recent genetic advances have shown there is a problem with gene expression in HD that happens before symptoms of Huntington’s disease occur.

Investigating a Huntington’s Disease Pathway

One pathway involved in changes in gene expression is known as the Hippo pathway and it plays a critical role in cell survival and death. While activation of the Hippo pathway increases resistance to cancer, too much Hippo activation can cause cell death. Interestingly, patients with HD and other neurodegenerative diseases have a lower incidence of cancer, demonstrating that Hippo activity is increased in HD and may kill off neurons.

Understanding how the Hippo pathway is activated and regulated can provide critical information for researchers pursuing new therapies for cancer and HD.

Dr. Sadri-Vakili’s lab is focusing on understanding what the level of Hippo pathway activation is in the human brain affected by HD.

Her team has determined that two major components of the Hippo pathway malfunction in Huntington’s disease. Specifically, decreasing MST (an enzyme that adds phosphate groups to other proteins) and thereby increasing YAP (a protein that eases gene expression), may reduce cell death in HD.

This discovery offers great promise for identifying therapies that can slow the progress of HD and may move us closer to a cure. MIND relies on the generosity of our patients, families and friends to help us keep the momentum of this research going and move the promising findings from the lab to our patients’ bedsides.

To learn more about how you can support Huntington’s disease research at Mass General, please contact us

MIND: Collaborating for a Cure

The MassGeneral Institute for Neurodegenerative Disease (MIND) is committed to finding treatments and cures to improve the lives of patients with neurodegenerative disorders including Alzheimer’s, Amyotrophic Lateral Sclerosis (ALS), Huntington’s and Parkinson’s disease.

Founded in 2001, MIND unites scientists and physician-scientists across disciplines with the common goal of translating laboratory findings into therapies that can reach patients in the clinic. Researchers in MIND laboratories work collaboratively to achieve the most promising results.

To learn more about MIND, please visit our website.