SRX246 is an investigational medicine being developed by Azevan Pharmaceuticals to potentially treat neuropsychiatric symptoms in Huntington’s disease and other neurodegenerative disorders like Alzheimer’s disease, intermittent explosive disorder, and post-traumatic stress disorder.

How SRX246 works

SRX246 is a medicine that blocks a receptor in the brain called the vasopressin 1a (V1a) receptor. It is therefore called a V1a antagonist.

Vasopressin is a small molecule normally produced by the body, which is thought to be involved in social and emotional behaviors. In Huntington’s disease, the body makes too much vasopressin, causing behaviors of stress, fear, aggression, depression, and anxiety.

The V1a receptor is the main receptor for vasopressin in the nervous system. By blocking the V1a receptor, SRX246 prevents vasopressin from binding to the receptor and causing the irritable and aggressive behaviors commonly observed in people with Huntington’s disease.

SRX246 in clinical trials

Preclinical studies with animal models of mood disorders initially highlighted the potential effectiveness of vasopressin antagonists in the treatment of neurodegenerative disorders. One study used magnetic resonance imaging (MRI) in rats to show that drugs that block vasopressin neurotransmission suppressed electrical activity in the region of the brain that is responsible for aggressive motivation. Another study showed that SRX246 and another drug candidate from the same class known as SRX251 were able to penetrate the central nervous system efficiently, reaching high levels in the brain.

Based on these findings in animal models, SRX246 moved to human studies and its safety and tolerability were assessed in healthy volunteers.

SRX246 is currently being investigated in a Phase 2 clinical trial (NCT02507284) called STAIR. The trial will evaluate the tolerability, safety, and effectiveness of SRX246 in the treatment of irritability in people with Huntington’s disease. It is currently recruiting up to an estimated 108 participants at 22 locations across the U.S. To be eligible for the study participants must have Huntington’s disease with irritable and aggressive symptoms.

During the trial, two-thirds of all participants will receive SRX246 in two different doses (120 and 160 mg), while the others will receive a placebo, both taken orally and twice a day.

The primary goal of the study is to determine the tolerability of SRX246 measured by the percentage of participants taking the medicine who complete the study. The secondary goal is to determine whether SRX246 is safe for patients. This will be measured by the proportion of participants who experience an adverse effect. The third and final goal is to examine several measures of irritability and other behavior issues in patients to evaluate whether SRX246 is effective and helpful in decreasing these symptoms.

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