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UI team works on brain drug

BY ALEKSANDRA VUJICIC | OCTOBER 09, 2014 5:00 AM

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For individuals who suffer from a traumatic brain injury or a neurodegenerative disease, it may seem like there is no hope.

But one team of University of Iowa researchers may offer some optimism as they progress toward a possible drug that could protect and preserve brain cells in situations where they would normally die.

In 2010, UI neuroscience Associate Professor of Andrew Pieper discovered a compound that could block cell death in the hippocampus of the brain, important for learning and memory. Pieper was an assistant professor at the University of Texas-Southwestern in Dallas when he made the discovery in collaboration with Joseph Ready and Steven McKnight.

Pieper came to the UI two years ago, where the compound has been further tested.

When Pieper found this particular class of compounds, called P7C3, he tested whether or not it would work on other types of neurons.

He found the compound achieved a dramatic protective effect in more than one area of the brain.

“It has pretty broad utility throughout the nervous system to protect nerve cells from dying,” he said.

Pieper said the molecule could not only block cell death but also prevent the degeneration of axons, which facilitate communication between brain cells, after injury to the brain.

“It’s like giving the brain an extra reserve of energy essentially, to repair itself and to compensate for injury,” Pieper said.

So far, mice and rats have been the only test subjects used.

Pieper and his team of researchers looked at different models of traumatic brain injury, one of which involved sending shock waves to the head of a mouse. In human cases, this can be comparable to being in the vicinity of a bomb explosion.

The compound was administered to the mice 24 to 36 hours after the injury.

“After the shock wave goes through the head the first thing that happens is the axons, that allow brain cells to communicate with each other, degrade from the physical force of the blast and that’s what we’re able to block,” Pieper said.

With the presence of this molecule, the mice showed normal learning and memory skills along with motor coordination after the injury.

Along with traumatic brain injuries, some researchers have studied the compound’s effect on neurodegenerative diseases such as Parkinson’s, a common movement disorder.

Roughly 60,000 Americans are diagnosed with Parkinson’s disease each year, and an estimated 10 million people worldwide, according to the Parkinson’s Disease Foundation.

“Parkinson’s disease is a disease in which a lot of neurons die, so we tried to use this compound to protect against some of the effects of neurodegeneration,” said Kumar Narayanan, a UI assistant professor of neurology who specializes in Parkinson’s disease.

Hector De Jesus-Cortes, a fourth year graduate student at UT-Southwestern, came to the UI to join Narayanan’s efforts. They used models in which rats were induced with a drug that caused dopamine neurons to die in a region of the brain associated with Parkinson’s disease.

The compound seemed to protect the neurons even after they had started to die, Narayanan said.

“It’s pretty exciting,” he said. “This could be protective in whatever is causing neurons to die during Parkinson’s disease.”

De Jesus-Cortes said throughout his years of research on the compound one of the most important things the compound is able to achieve goes beyond just a molecular level of protection.

“We’re not only protecting the cell, or the neuron, but we are also protecting the behavior, which is always a goal in neuroscience,” De Jesus-Cortes said. “We want to show this at the molecular level and the behavioral level because that’s human.”

Before the potential drug can reach human trials, it must go through rigorous toxicity testing. The time frame could vary based on toxicity test results in two different animal species. Pieper and his team have partnered with Calico, a Google biotech company, to assist them during the process of drug development.


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