February 10, 2016 – Daniel Laskowitz, MD, MHS, and researchers at the DCRU are studying a new drug that might help the brain protect itself against serious damage.
Researchers at the Duke Clinical Research Unit (DCRU) are taking the first steps toward a new treatment for acute brain injury. If their efforts are successful, it could be the first treatment of its kind for patients.
Traditionally, treatment options for patients with acute brain injuries—such as those resulting from car accidents or combat situations— have been limited to surgery to reduce pressure inside the skull and medications to prevent seizures and limit fluid retention. But a new discovery might lead to a treatment that could allow the brain to protect itself from the most severe effects of these types of injuries.
“No pharmacological agent to date has ever been shown to reduce brain injury,” said the DCRI’s Daniel Laskowitz, MD, MHS (pictured). “What we have done is to create a potential therapy for acute brain injury based on a naturally occurring protein that seems to modify outcomes for patients with brain injuries.”
Laskowitz and his colleagues have evaluated the mechanisms by which different isoforms of apolipoprotein E (ApoE) can influence patient outcomes after acute brain injury. Different variants of ApoE have previously been linked to Alzheimer’s disease and various cardiovascular ailments. The Duke researchers have spent more than 20 years examining how this protein can also affect how people respond to brain injuries.
The culmination of this research is CN-105, a small peptide derived from the receptor binding region of ApoE. The peptide is already known to improve outcomes in a number of animal models of brain injury. CN-105 is believed to work by blocking the brain’s inflammatory response to injury, and the researchers think the peptide could be used to treat intracranial hemorrhage, stroke, and other forms of acute brain injury.
Intracerebral hemorrhage, or bleeding within the skull, accounts for between 8 and 13 percent of all strokes, and is more likely to result in death or major disability than ischemic stroke or subarachnoid hemorrhage. Intracerebral hemorrhage and accompanying edema can also disrupt or compress adjacent brain tissue, leading to severe neurological dysfunction.
Now a team of researchers led by DCRU Associate Director Jeffrey Guptill, MD, are beginning the first in-human trials of CN-105 to see if the peptide could be a viable treatment for these patients. The team is roughly halfway through a single-dose escalation trial in healthy volunteers to determine the drug’s safety and efficacy. The next step for this compound is a phase II study, which is anticipated to start in the fall of 2016.
Although there is still much work to do, Laskowitz is optimistic that the years of research will eventually pay off.
“This would be the first neuroprotective drug of its kind,” he said. “Our hope is that we will finally have something to help people who otherwise would have very few options.”