08:00pm Friday 20 October 2017

UNMC takes next step in developing Parkinson’s disease vaccine

The findings appear in the March 1 issue of the Journal of Immunology, a leading scientific journal in the field of immunology.

 
The cause of Parkinson’s disease is the loss of neurons which produce dopamine, a nerve signaling chemical that controls movement and balance. The Parkinson’s Disease Foundation estimates that about 1 million people in the United States and more than 4 million people worldwide have the disease.
 
Degeneration and loss of these dopamine-producing neurons typically occur after age 60, and it is estimated that one person in 20 over the age of 80 has Parkinson’s.
 
Neurodegeneration occurs when a normal protein called alpha synuclein clumps, changes shape, then accumulates in the brain. This results in the body attacking it through inflammation and causing destruction of dopamine-producing nerve cells.
 
In the study, researchers reversed the neurodegenerative effects of alpha synuclein by changing immune responses to it. The vaccine strategy trains the immune system for eliciting neuroprotective responses in damaged brain regions.
 
In mice with an experimental form of Parkinson’s disease, injection of the vaccine produced cells that were able to reverse the disease. After receiving the treatment, these mice were found to have a similar number of dopamine-producing nerve cells and fibers as mice without Parkinson’s.
 
“We believe this could be a revolutionary means for Parkinson’s disease therapeutics,” said Howard Gendelman, M.D., who partnered with R. Lee Mosley, Ph.D., to lead the research. “It has been a long journey representing more than 10 years of hard work by our research team.”
 
The researchers found that the vaccine enabled T cells in the treated mice to migrate to the damaged area of the brain and triggered a neuroprotective response that reduced disease-linked reactions in the brain.
 
T cells are white blood cells that are of key importance to the immune system and are at the core of adaptive immunity, the system that tailors the body’s immune response to infectious organisms. The T cells act like soldiers who search out and destroy the targeted invaders.
 
“The identical immune deficits seen in mice are being looked at in humans with Parkinson’s disease,” Dr. Mosley said. “Early results are encouraging. This should pave the way for researchers to begin follow-up studies on the Parkinson’s treatments and open up new opportunities to realize an immunization approach for other neurodegenerative disorders such as Alzheimer’s disease and amyotrophic lateral sclerosis (Lou Gehrig’s disease).”
 
Dr. Gendelman said additional work is needed to determine how to translate the study results into a therapy for humans and to make sure the treatment is safe for patients.
 
Human studies are being conducted at the University of Alabama-Birmingham and within the next month at UNMC to determine if the immune deficits seen in mice also are present in humans with Parkinson’s disease. Such studies are required before vaccine trials are performed in humans, Dr. Gendelman said. This phase of the research is being made possible through funding from the Shoemaker Foundation in Nebraska.
 
James Linder, M.D., CEO of UNeMed, UNMC’s technology transfer company, said UNeMed has filed a patent application on the vaccine and will soon commence discussions with commercial partners on bringing the vaccine to the clinical setting.
 
Dr. Gendelman is professor and chairman of the UNMC Department of Pharmacology and Experimental Neuroscience (PEN). Dr. Mosley is associate professor in the PEN department. They teamed with three graduate students, Ashley Reynolds, Ph.D., David Stone and Jessica Hutter, who were responsible for performing the study and analyzing its results.
 
As the state’s only academic health science center, UNMC is on the leading edge of health care. Breakthroughs are possible because hard-working researchers, educators and clinicians are resolved to work together to fuel discovery. In 2009, UNMC’s extramural research support topped $100 million for the first time, resulting in the creation of 3,600 jobs in Nebraska. UNMC’s academic excellence is shown through its award-winning programs, and its educational programs are responsible for training more health professionals practicing in Nebraska than any other institution. Through its commitment to education, research, patient care and outreach, UNMC and its hospital partner, The Nebraska Medical Center, have established themselves as one of the country’s leading health care centers. UNMC’s physician practice group, UNMC Physicians, includes 550 physicians in 50 specialties and subspecialties who practice primarily in The Nebraska Medical Center. For more information, go to UNMC’s Web site at www.unmc.edu.
 
 

What others are saying:
 
“Dr. Gendelman and his team are to be congratulated for their important insights as to why dopamine-producing cells die and how to rescue these cells, which are the pathological hallmark in Parkinson’s disease. This seminal work is extremely significant since it provides a cogent rationale for immune-based strategies in human Parkinson’s disease and a unique and important opportunity to develop novel neuroprotective therapies.”
 
Stanley Appel M.D., chairman, neurology, Methodist Neurological Institute, Houston
 
“I think this work is really important. The studies in this new report, along with other data from the Gendelman group, our own lab, and others are leading to a completely new way of thinking about the role of immunity in PD. The new information points to a central role of the immune system as a causative element of the Parkinson degenerative process.
 
“This work leads to the idea that it might be possible to develop a vaccine which could alter immune responses in human PD and slow or prevent the progression of Parkinson’s disease. This concept would most likely have been dismissed as a ‘crazy idea’ just a few years ago, but these studies put the proposal on solid scientific footing. If we can confirm Dr. Gendelman’s findings in humans, this would open the door to an important new class of therapies for Parkinson’s disease.”

David Standaert, M.D., Ph.D., professor and vice chair, neurology, University of Alabama at Birmingham (UAB), who is collaborating with Dr. Gendelman by studying T cell functions in Parkinson’s patients
 
“This discovery has the potential to impact millions of people affected by Parkinson’s disease. We are very enthusiastic about finding a company to help bring this technology through the clinic.”
 
Michael Dixon, Ph.D. president, UNeMed Corporation, technology transfer company for UNMC
 
“As a treating physician, using medications or surgical interventions to manage the disabling symptoms of Parkinson’s disease is rewarding. But having the possibility to alter the course of the disease would be revolutionary. The successful approach to a vaccine in a mouse model of Parkinson’s disease opens new treatment horizons. If eventually proven to have similar effectiveness in humans, such a vaccine could dramatically change what can be done about Parkinson’s disease. I am proud of our efforts at UNMC to treat and find a cure for Parkinson’s disease and other movement disorders.”
 
Diego Torres-Russotto, M.D., assistant professor, neurological sciences, and director of UNMC Movement Disorders Program

 For more information, please contact :

Tom O’Connor, UNMC Public Relations, (402) 559-4690 (402) 650-7063


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