KU Medical Center researcher testing drug to improve concussion symptoms

Right now, the treatment for most people with concussions is simply to rest their brain by limiting physical and mental activities. Michael Rippee, M.D., associate professor of neurology at the University of Kansas School of Medicine, is partnering with a company to research a new drug treatment that might be a significant improvement over dark rooms and reduced activity.

“This could also be a critical step forward for the 20% or more of patients who have ongoing symptoms or have trouble with daily activities,” Rippee said. “Concussions can lead to a lifetime of health issues, including chronic headaches, depression, problems with thinking and memory, vision and balance issues, and sleep disorders.”

Rippee and his team have completed a pilot study testing ghrelin, a multifaceted gut hormone known for its stimulatory effects on food intake, fat deposition and growth hormone release. Famously known as the “hunger hormone,” ghrelin is being developed synthetically as a concussion drug, OXE103, by Oxeia Biopharmaceuticals, which sponsored this clinical trial of off-label use with the University of Kansas Medical Center.

A concussion is a mild traumatic brain injury that occurs when a head injury causes the brain to move back and forth against the walls of the skull. Concussions can result from falls, car accidents or sports injuries. According to multiple studies, concussions are a common reason to seek medical treatment, and a study done by National Public Radio found that nearly one in four Americans reported sustaining a concussion, with a third of those experiencing long-lasting symptoms.

Many studies have shown that 5-10% of athletes experience a concussion in any given year. As medical director of the Center for Concussion Management at The University of Kansas Health System, Rippee sees a lot of patients with concussions.

“During a concussion, the blow to the head causes the brain to discharge its energy like the draining of a battery,” Rippee said. “In addition, the movement of the brain within the skull during injury can lead to stretching damage to axons [parts of neurons that transmit electric impulses]. This damage can slow down or inhibit information transfer between nerve cells. Both the lack of energy and lack of effective information transfer in the brain results the symptoms we associate with concussion, such as problems with thinking, difficulty with emotions and issues with body function.”

The clinical trial involved 21 participants who had experienced a concussion within 28 days of the beginning of the study. Trial participants self-injected themselves with OXE103 twice a day for 14 days.

OXE103 is not a new drug, but it has never been studied in concussion. “It’s a synthetic version of a hormone that is produced in the stomach and enters the brain,” Rippee said. “As a natural hormone product, it has been shown to be very safe and is well tolerated.”

Rippee’s study found that trial participants significantly improved versus those who received a standard treatment of rest. Participants improved their scores on a test measuring quality of life after brain injury while reducing their scores on a post-concussion symptom test.

“I am encouraged by the results we are seeing from the trial,” said Michael Wyand, Ph.D., chief executive officer of Oxeia Biopharmaceuticals. “The data provide hope for an effective treatment for the millions of people who suffer ongoing post-concussion symptoms as a result of a lack of effective treatment options.”

Preclinical models have shown that ghrelin impacts both the neurometabolic cascade, the disorder of the physiologic process that is characteristic of a concussion, and the associated axonal damage.

“While we recognize the limits of this study, including a small sample size, the results indicate that ghrelin is a promising potential therapy to treat concussions soon after occurrence,” Rippee said, noting that a larger multi-center randomized trial will be an important next step.