UNC-Pembroke professor doing ‘important work’ – Fayetteville Observer

Michael Futch Staff writer @fo_futch

PEMBROKE Ben Bahr is not one to say he's going to cure Alzheimer's.

But the University of North Carolina at Pembroke faculty member regarded as an expert on age-related neurodegenerative disorders strives to be an important link in the research chain that may one day lead to a remedy for the irreversible, progressive brain disorder. He knows it's going to take the work of many researchers the world over to overcome Alzheimer's and other similar conditions that can destroy a person's mind.

Inside the William C. Friday Lab found at the back of the Office for Regional Inquiries on the grounds of the COMtech Center, roughly five miles from the main college campus Bahr and his small group of researchers and biotechnology students are pursuing a treatment pathway no one has ever shown before. They carry on work to test a drug compound that Bahr stumbled on by mistake about two decades ago when he was working on his post-doctorate. It is one that may help clear the tangle of toxic proteins thought to contribute to Alzheimer's disease.

The hope is that this compound abbreviated as PADK can slow and even reverse the progression of the disease that affects an estimated 5.5 million Americans. Alzheimer's is the most common form of dementia, and one in 10 people ages 65 and older have the disease, according to the Alzheimer's Association.

Over the last 16 years, traumatic brain injury has drawn considerable attention and remains an important public health problem, in part, because of the thousands of cases that have emerged among active military personnel engaged in the Iraq and Afghanistan conflicts.

Traumatic brain injury and post-traumatic stress disorders are signature injuries of those wars and have been linked to an increased risk of Alzheimer's disease and other dementias. Some of Bahr's work on blast-induced brain injury, funded by grants from the Department of Defense and Army Research Office in Raleigh, has resulted in the discovery of "very subtle" changes to synaptic proteins and the circuitry of the brain. This could explain personality changes from a slowing down of how brain nerve cells send messages to each other.

Bahr, who is 55 and a native of Escondido, California, arrived in Pembroke in 2009, after being designated the William C. Friday chair and distinguished professor at UNC-Pembroke. That appointment carried with it a couple of hundred thousand dollars to set up his lab as well as a salary stipend.

Before that, Bahr spent nearly 12 years on his research as a faculty member at the University of Connecticut.

"He was looking to make a move from where he was in Connecticut. I think it had a lot to do with lifestyle, for both he and his wife," UNC-Pembroke Chancellor Robin Cummings said. "He was looking at Hawaii. I can say he chose Pembroke over Hawaii."

For his work in the field of Alzheimer's disease research, the University of North Carolina system named Bahr the 2017 O. Max Gardner Award winner in May. Selected by the UNC Board of Governors, the honor recognizes faculty who have "made the greatest contribution to the welfare of the human race."

Bahr teaches the course, the Principles of Medical Biotechnology, at the Robeson County college, established in 1887 by American Indians to train Indian teachers to teach Indian youth. Today, this masters degree-granted institution boasts a diverse enrollment of about 6,400 students.

"It's the highest award a faculty member of the UNC system can receive, in terms of being able to do research and teach," Cummings said. "At Pembroke, it's huge on several levels. It shows you can make contributions that make an impact even from Pembroke and Robeson County. From a modest lab surrounded by cornfields. That speaks volumes."

The recognition is not the first to trickle down Bahr's way. Four years ago, the Board of Governors also awarded him the James E. Holshouser Jr. Award for Excellence in Public Service for Alzheimer's disease awareness.

"You can do research anywhere. Give me a freezer and a chopper," he said. "I can get more work done here. Here, they gave me a lab and said, 'Do important work.' "

Bahr views the honors as more recognition for the lab. In humble fashion, he embraces the personal kudos as a huge team effort.

"I'm not in the lab," he said during an interview from his office on the outskirts of town. "I'm in here trying to raise funds, trying to write papers. I design experiments, but I need a good research team. So this is definitely a team effort. If I don't have a good team, I can't make heads or tails out of the data. And I keep them enthusiastic because they want to learn how the brain works.''

In a related laboratory endeavor, members of Bahr's team are studying traumatic brain injury and other types of neurotrauma for military purposes. Based on that research, Bahr believes that combat-related blast waves are likely impacting the same pathways in the brain that affect Alzheimer's. He thinks it's likely that blast-induced changes in the brain could be producing a boost to Alzheimer's problems, increasing the risk of the dementia that may show up at an earlier stage.

As of 2016, the Defense and Veterans Brain Injury Center of the Department of Defense had reported 361,092 cases of service members diagnosed with traumatic brain injury since 2000. The majority of these impairments sustained by members of the Armed Forces are classified as mild traumatic brain injury, according to the center.

In March 2016, Fort Bragg and Womack Army Medical Center opened the $11 million Intrepid Spirit Center to treat symptoms connected to traumatic brain injuries, chronic pain and psychological health conditions like post-traumatic stress. At the time, Fort Bragg reported an increase in traumatic brain injury evaluations.

On Wednesday, Dr. Don Algeo, an Army colonel and deputy commander of medical services on Fort Bragg, said the post has been seeing several hundred traumatic brain injuries a year since the Afghanistan War started in 2001. Before the center opened, he said, Fort Bragg operated a similar clinic that functioned as an Intrepid Spirit team.

"Hundreds of mild to moderate, with rare severe traumatic brain injuries, come through Womack," Algeo said. "We're actually seeing a decrease of combat-blast brain injuries. We're still seeing the same number of training injuries. But the combat-blast TBIs have gone down" over the last 18 to 24 months.

Other studies conducted in the William C. Friday Lab have looked at how the drug compound and its derivatives work on the clustering of the toxic proteins in models of Parkinson's disease and frontal temporal dementia.

Bahr said there are probably thousands of risk factors for Alzheimer's. Being dropped on your head as a baby, he offered as an example, may increase one's risk of Alzheimer's. With the study of traumatic brain injury, his team is trying to understand about blasts and the suitable markers for blast-induced mild TBI. An MRI is unable to see subtle changes in a person's circuitry.

"We're still discovering how the brain works every day," said Bahr, whose disheveled laboratory appearance on this Thursday in June matches his distinguished salt and pepper beard with an ill-fitting striped sports jacket that usually hangs in his office. "I would love it if we could fix Alzheimer's, and I think we're on a path. I've been saying for 20 years that drug companies are spending too much money on the direction they were taking. Focusing too much on a tiny little protein. Drug companies are very good at turning off enzymes that block the bad protein. That was the most logically straight-forward pathway. That turned out to be very difficult, because if you block an enzyme, that same drug might be blocking important things the enzyme might be doing."

Bahr and his team have taken a different approach with PADK, the drug compound he found by mistake at the University of Connecticut while researching different means of eliminating the Abeta protein plaques. At the time, he was using a highly concentrated formula of PADK when it occurred to him to try a watered-down version. The result in this "Eureka" moment?

The implication was that it enhanced lysosomal capacity, increasing the enzyme function in the brain. It's this enzyme, he said, "that helps chew the bad proteins."

In Alzheimer's and Parkinson's diseases, certain proteins in the brain stick together in toxic, knotted clumps that cause cognitive decline. An example in Alzheimer's disease is tau protein, which has been called an often overshadowed counterpart to the more heavily studied amyloid beta protein.

The toxic proteins can accumulate for up to 20 years before memory problems begin to show, according to Bahr. In the huge field of Alzheimers researchers, brain scans have been developed that can detect the accumulation of the amyloid and tau proteins before a person reaches the cognitive state of Alzheimer's disease. The scans may provide a more accurate predictor before someone develops serious issues with memory loss.

Based on the Bahr team studies, treatment would begin at a much earlier phase, before the gradual buildup of bad protein in the brain. Before patients develop problems with recall. The first drug his research team worked with, in both cultured brain slices and mouse models of Alzheimer's disease, carries the long name of carbobenzoxycarbonyl-L-phenylalanyl-L-alanyl-diazomethylketone. Or, much simpler, PADK.

"So the work we're doing right now is trying to confirm this avenue of treatment can actually slow down the gradual protein accumulation pathology before you reach the Alzheimer's phase," Bahr said. "You need to start being treated so you don't get Alzheimer's. But treated with what is the big question. There is nothing there, but the drug class we're developing is exactly that drug you want to start giving to people that have early protein accumulation events that tell you they're on their way to Alzheimer's disease. And they're using those scans now in clinical tests so you can tell which people are on the way to Alzheimer's."

Though he can be plain-spoken, an interview with Bahr about his team's research is peppered with such scientific jargon as:

Neurons (nerve cells in the brain)

Lysosomes ("tiny little garbage disposals," as he describes them, "inside each brain cell")

Hippocampus (thought to be one of the most important areas of the brain for memory)

Axons (long wires that allow neurons to talk to each other inside the brain)

Synapse (the very end of the axon, where two neurons are making a connection and where memories are formed)

Synaptic mechanisms (how memories are encoded)

"He can either talk scientifically to you or put it in layman's terms," said Heather Romine, his lab manager who has worked with Bahr for 6 1/2 years at UNC-Pembroke. "People appreciate it more when you can put it on a level they understand."

Dr. Ralph Nixon, the director of the Center for Dementia Research at the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, New York, worked in a parallel area of research while Bahr was doing post-doctoral work at the University of California-Irvine. He said he has known Bahr since the 1980s and that Bahr's work is making a difference in the field of Alzheimer's research at UNC-Pembroke.

"I think he has been a champion for the idea that the lysosomal system is disrupted in various diseases in aging and that it is a good target for therapy," he said. "I think more and more people are agreeing with that. We've always shared that view. I think the field has evolved to accept it and that it's true. Lysosomes are a prominent aspect of the ideology of the pathogenesis cause of diseases like Parkinson's and Alzheimer's."

Until recently, Nixon said, the ideas surrounding lysosomes were not as ensconced in the mainstream as they are now. Bahr's approach was broader than a specific disease, which Nixon said, turns out to be a correct view of the tissues. Bahr's general strategy of enhancing lysosomal function and trying to make enzymes in lysosomes work better is of strong interest to the neurodegenerative field, he concluded.

"People in the Alzheimer's field and the aging field know him pretty well because his work is more fundamentally related to neurodegenerative disease more broadly," Nixon said. "He's not necessarily identified with one disease."

Bahr, who studies the human organ that serves as the center of the nervous system, was initially intrigued by the solar system and space beyond. He cites the influence of his late father, Lyle, for this early interest in the universe.

During the 1950s, the elder Bahr worked with General Dynamics in San Diego while the company was working on missiles and the different rockets that ended up being the ones needed for the Saturn and Atlas families of American rocket boosters. Lyle Bahr also was employed for a time by Rocketdyne, which became the major supplier for NASA's development efforts, supplying all the major engines for the Saturn rocket.

"He's one of the million or so people that helped get us up there," Bahr said.

As for Bahr's mother, Anna, he attributes her with instilling in him a devoted work ethic. She was a beautician, and he saw how hard she worked to get him through college, the first in his family to earn a diploma from a four-year institution.

Bahr sought to become a cosmologist, studying the cosmos. But the California Institute of Technology turned him down when he applied after high school. Instead, the University of California, Santa Barbara, admitted him as a student, and the direction of his life and career would change course like the stars in the sky.

There, he caught the research bug as soon as he was introduced to the basis of neurons, how the complicated brain is designed and how the brain codes memory forever.

He believes he chose the right path. Bahr talks about his brain being more linked to biology than the physics of the universe. At Santa Barbara, he would earn his bachelor's degree in molecular biology and biochemistry and later a doctorate in chemistry.

"The universe is like the brain," he said. "Billions of stars vs. billions and billions of neurons. As soon as I saw the complexity of the brain that's what got me interested. Why do we remember a phone number we remember all our lives? I can tell you the phone number of my girlfriend in high school. Why does my brain hold that number? It's not a single cell that remembers that number. It's something that got changed in my head, and it's there forever.

"I know how cells work," he said. "Cells make proteins; cells get rid of proteins. There are glycosylation events. Phosphorylation events. These tiny little changes that happen all the time. But all these changes only last a few hours or days. So how is a memory stored in our heads for 80 or 90 years, or however long I live?"

It was at Connecticut that Bahr submitted his first patent with the idea for treatment of Alzheimer's. That patent now hangs on his office wall. Since joining the faculty, he has submitted several related patents with the idea of not only treating Alzheimer's with this new way to get rid of proteins but also using a drug class that make lysosomes work a little better. As the brain ages, neurons get older and old lysosomes don't work as effectively as young lysosomes.

"I won't be able to solve Alzheimer's in my lifetime, likely," Bahr said. "If I don't do it, I want to at least put people out there that will be the next researchers using the next tools because I don't know how those brain scans work that can now detect proteins that build up in Alzheimer's. My students are going to do PhD programs and start using research methods and laboratory equipment that I've never heard of before because technology is progressing rapidly. If my drug class doesn't take off from the work I'm doing, I'm hoping at least new researchers keep up their enthusiasm from my lab and chase new ideas.

"They caught the bug of research, as I say."

Staff writer Michael Futch can be reached at mfutch@fayobserver.com or 486-3529.

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UNC-Pembroke professor doing 'important work' - Fayetteville Observer