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Mentor Fulbright Scholar to study way to treat Parkinson's disease

Tuesday August 21, 2012

Janet Pokolak

News-Herald of Northern Ohio - One day Patrick Chirdon's name may be linked with a cure for Parkinson's disease, which today affects about 3 percent of the older population.

The Mentor man, who recently graduated with honors from Case Western Reserve University in Cleveland, is off to Switzerland next month as a Fulbright Scholar to continue research he began in Northeast Ohio.

Chirdon found evidence that a thyrotropin-releasing hormone, called TRH, protects brain cells in a way that could make it an effective treatment against Parkinson's disease.

But it's the mice in Switzerland, not its storied scenery, that has excited Chirdon the most. The laboratory where he'll work is the Brain Mind Institute at the Ecole Polytechinque Federale de Lausanne (Swiss Federal Institute of Technology in Lausanne) — the only one in the world to develop a laboratory rat with a gene specific to his area of study.

"Their rat model is the only one to have the specific gene mutation (LRRK2) that's recognized as the most common genetic cause of Parkinson's," he said.

"I've come to the conclusion that drugs based on a structure of thyrotropin-releasing hormone may inhibit the LRRK2 enzyme and be an effective treatment for Parkinson's. It is my intent to study to effects of these drugs on these animals."

It's something that would need to be done before clinical trials with humans could be done, he said.

"And this is the only place in the world where it is possible."

His research at CWRU found that TRH helped to regrow neurons and minimize cell death in a brain region, known as the striatum, that is heavily affected by Parkinson's. The cell death of dopamine neurons leads to some of the motor symptoms of Parkinson's, he said.

The hormone is known primarily for affecting thyroid metabolism, but Chirdon found mounting evidence in spinal muscular atrophy and epilepsy that it helped protect neurons against toxicity and stressors. But the evidence was a review of literature, and the reality is what he needs to test in mice.

He first became interested in how the thyrotropin-releasing hormone works while working in the lab of the late Mark A. Smith, a professor of pathology and director of basic science research of the University Memory and Cognition Center. Smith, who was dedicated to teaching and mentoring students, infected Chirdon with his passion for science and pushed him to think critically.

"My inspiration for this project came directly from Dr. Smith," Chirdon said. "He had a huge impact on my career choice."

Because Chirdon's grandfather had Alzheimer's disease, his early studies went in that direction — another area of expertise for Smith.

In fact, Chirdon worked in Smith's Alzheimer's pathology lab at Case as well as the labs of Dr. Kingman Stohl and Dr. Pingfu Feng at the Veterans Affairs Hospital.

"I used human brain samples from Alzheimer's patients and age-matched controls to analyze thyrotropin-releasing hormone concentration in various brain regions," he said.

But after Smith was struck by a car and killed in December 2010, Chirdon no longer had a lab for his research. But his dedication didn't end.

He spent last summer studying in Baltimore with Dr. Bronwen Martin at the National Institutes of Health. As his research mentor, she invited Chirdon to be first author on a paper that proposes using thyrotropin-releasing-hormone-based drugs for Parkinson's disease treatment. It would serve as an alternative to the current treatment, which sometimes results in painful muscle spasms.

Not only was the paper submitted to the journal Current Alzheimer's Research, it also went to the Brain Mind Institute at the Swiss Federal Institute of Technology, Lausanne, as part of his application for a Fulbright Scholarship.

In her letter of recommendation to the Fulbright Program Selection Committee, Martin cited Chirdon's resourcefulness.

"He even translated some very relevant papers that were only available in Japanese," she wrote.

After graduating in 2008 from Mentor High School, Chirdon went to Case to study psychology. But it is the biology of the brain that has captured his interest. He hopes to go on to earn a doctorate degree in pathology but is leaving himself open for his year in Switzerland to help him further fine-tune his focus.

"It was determined that the TRH project would take longer than a year to complete and would cost more than I had requested from the Michael J. Fox Foundation, so it might be better for me to save it as a Ph.D. dissertation," he said.

Dr. Patrick Aebischer, one of a pair of doctors who will oversee Chirdon's work in Switzerland, said Chirdon will be able to use animal models with neurodegenerative diseases to investigate how pathology interacts with genes involved in the process of brain aging.

"During his stay in my laboratory, Mr. Chirdon will have full access to all available equipment," Aebischer wrote in his Fulbright Scholarship letter of affiliation. "A personal lab space, including a desk, will be provided, and Mr. Chirdon will be accredited as a member of the EPFL, which offers various activities on the campus."

That affiliation will allow him to explore Switzerland and nearby France in his free time. But for the next year he doesn't expect to have much in the way of free time.

The study I propose will take a year to complete working full-time," he said. "It helps that I speak German and have a working knowledge of French."

He said middle-aged rats — 17 months old — will be used because the thyrotropin-releasing hormone expression varies with age. Behavioral effects will be evaluated by using tests for motor activity.

"Aging research, which I am primarily interested in, is especially significant in Switzerland because of all the countries in Europe, it has the most people 100 years old and older," he said.

He's learned that 15,000 people in Switzerland are living with Parkinson's and hopes this research can help build a bridge between the U.S. and Switzerland with this collaboration.

In America, more than 50,000 cases of Parkinson's are diagnosed each year.