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Local drug developer targets traumatic brain injury

Animal trials show promise, according to university researchers.

July 29, 2016
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Tetra Discovery
Mark Gurney said the drug A33 could help with chronic traumatic encephalopathy, a condition in the spotlight due to concussions and brain injuries in the National Football League. Courtesy Adam Bird

Anyone who’s suffered or watched a loved one suffer from a traumatic brain injury will appreciate that a group of local scientists may have found a way to help the healing.

A potential therapy drug developed by Grand Rapids-based Tetra Discovery Partners is being tested by University of Miami researchers. If successful, the drug would help victims of traumatic brain injury improve learning and memory.

“Concussions are all too common. Most people injured by a concussion recover, although that may take weeks to months. However, four (to) five million Americans sustaining a brain injury fail to recover completely and live with chronic disability,” said Mark Gurney, Tetra chairman and CEO.

Gurney said the drug, called A33, has the potential to help some people who have sustained multiple concussions and developed a severe condition known as chronic traumatic encephalopathy or CTE.

A33 is something called a selective phosphodiesterase 4 subtype inhibitor, or PDE4B.

“The PDE4B inhibitor has the potential to treat chronic disability after brain injury,” Gurney said.

A new report on the drug’s development was recently published in this month’s edition of the Journal of Neuroscience. The report was prepared by Coleen Atkins, associate professor in the University of Miami’s department of neurological surgery, W. Dalton Dietrich, Ph.D., scientific director of The Miami Project, and Gurney.

Dalton and Atkins approached Tetra soon after the company began operations in 2011, Gurney said.

“(This is) exciting data that shows that chronic disability due to brain injury may be treatable with a drug. Given the large and expanding unmet need among patients, and the realization that multiple concussions may have devastating impact on the brain, Tetra is viewed as an innovative, high-potential company in this sector,” he said.

Gurney said Tetra has spent upward of $4 million so far to develop the drug.  The development effort has been funded by Small Business Innovation Research grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

TBI is caused by impact to the head, and Gurney said one of the most common problems facing victims afterward has to do with memory and learning. About eight out of 10 people with TBI have to cope with learning problems in the months that follow the injury, he said.

Tetra has been testing its drug on rats with TBI. Three months after the rats’ injury, the researchers gave the animals the inhibitor and then checked their learning and memory behaviors.

“Treating TBI survivors during the months to years after brain trauma is a very promising area of research, and several clinical trials are already tackling this problem by using drugs repurposed from other neurological disorders such as Alzheimer’s disease,” Dietrich said.

“This selective PDE4B inhibitor from Tetra Discovery Partners has great promise, restoring the learning and memory performance of TBI animals to nearly non-injured levels. This project represents an excellent example of a collaboration between academic researchers studying animal models of brain injury and a biotech company with expertise in human clinical trials.

“We expect that this collaboration with Tetra will yield a new clinical trial using this therapeutic strategy in human TBI survivors.”

According to Gurney, the inhibitor significantly reversed the deficits in the rats’ memory problems caused by TBI. Tetra’s timeline is to enter human clinical trials in 2017.

“The compound used by the Miami researchers was an early compound that required further chemical optimization. Tetra is working on a second-generation compound that will be effective in people. Three months after brain injury, the rats are unable to learn simple tasks.  Dosing once daily with the PDE4B inhibitor restores learning and memory on multiple behavioral tests to near normal levels,” he said.

“We know this type of drug works in rats. We now need to show in well-controlled clinical trials that it benefits people with chronic disability due to brain injury.”

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