If confirmed in additional laboratory research and clinical trials, the researchers’ study in mice engineered to have Parkinson’s disease symptoms could pave the way for a Parkinson’s disease therapy based on the hormone irisin.
Johns Hopkins Medicine’s Ted Dawson, and the Dana Farber Cancer Institute’s Bruce Spiegelman worked together to look into the link between the exercise molecule irisin and Parkinson’s disease.
In the past decade, other laboratories have found that exercise elevates levels of irisin, and there is interest in looking into the connection between irisin and Alzheimer’s disease as well as Parkinson’s disease.
In the laboratory model, the researchers found that irisin prevented the accumulation of alpha synuclein clumps and its associated brain cell death.
Next, the research teams tested irisin’s effects on mice engineered to have Parkinson’s-like symptoms. They injected alpha synuclein into an area of the mouse brain, called the striatum, where dopamine-producing neurons extend. Two weeks later, the researchers injected a viral vector, which increased blood levels of irisin, which can cross the blood-brain barrier, into the mice.
Six months later, mice that received irisin had no muscle movement deficits, while those injected with a placebo showed deficits in grip strength and their ability to descend a pole.
The researchers demonstrated that irisin also speeds up the transport and degradation of alpha synuclein via fluid-filled sacs called lysosomes in brain cells.
“If irisin’s utility pans out, we could envision it being developed into a gene or recombinant protein therapy,” says Dawson, referring to the widening field of drug development aimed at using cellular genetics to treat disease. Dawson is a professor in neurodegenerative diseases, a professor of neurology, and director of the Johns Hopkins Institute for Cell Engineering.
“Given that irisin is a naturally produced peptide hormone and seems to have evolved to cross the blood brain-barrier, we think it is worth continuing to evaluate irisin as a potential therapy for Parkinson’s and other forms of neurodegeneration” adds Spiegelman.
Dawson and Spiegelman have filed for patents on the use of irisin in Parkinson’s disease. Spiegelman has created a biotechnology company, Aevum Therapeutics Inc., based in Boston, to develop irisin into treatments for neurodegenerative disease.
Additional scientists who contributed to the research are from Johns Hopkins and Harvard Medical School.
Funding for the research came from the JPB Foundation, the Maryland Stem Cell Research Fund, the Mark Foundation for Cancer Research, the Damon Runyon Cancer Research Foundation, and Deutsche Forschungsgemeinschaft.