A hormone called irisin, which is secreted into the blood during aerobic exercise, has been found to reduce levels of alpha synuclein, a protein linked to Parkinson’s disease (PD), and halt movement problems in mice. The new work could pave the way for a therapy for PD if confirmed in additional laboratory research and clinical trials.
The work was led by Ted Dawson, MD, PhD, from Johns Hopkins Medicine and Bruce Spiegelman, PhD, from the Dana Farber Cancer Institute in Boston. They published their study in the Proceedings of the National Academy of Sciences “Amelioration of pathologic alpha-synuclein-induced Parkinson’s disease by irisin”.
PD is a neurologic condition that causes people to lose control over their muscles and movements, and endurance exercise has long been known to alleviate symptoms of it.
“Physical activity can prevent and ameliorate the symptoms of multiple forms of neurodegeneration, including Alzheimer’s disease (AD) and PD,” the researchers wrote in their article. “[I]risin carries some of the benefits of exercise to adipose tissues, [so] we and others have begun to study the effects of irisin in various models of neurodegeneration.”
The team used a cell culture model in which alpha synuclein proteins clump in a way that is very similar to what occurs in the brains of people with PD. The clumps kill dopamine-producing brain cells, a key trigger of Parkinson’s disease. In the laboratory model, the researchers found that irisin prevented the accumulation of alpha synuclein clumps and associated cell death.
Next, the researchers 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 into the mice to increase the blood levels of irisin, which can cross the blood-brain barrier. Six months later, mice that received irisin had no muscle movement deficits, whereas those injected with a placebo showed deficits in grip strength and their ability to descend a pole.
Additional studies of brain cells of the mice given irisin showed that the exercise hormone lowered levels of PD-related alpha synuclein between 50% and 80%. The research team demonstrated that irisin also speeds up the transport and degradation of alpha synuclein via fluid-filled sacs called lysosomes in brain cells.
“The major phenotypic conclusion of this paper is that irisin prevents the degeneration of [dopaminergic] neurons and thereby reduces the motor deficits induced by pathologic alpha-syn,” the researchers wrote. “Mechanistically, it appears that irisin reduces the level of pathologic alpha-syn at least in part, through increasing the lysosomal degradation of pathologic alpha-syn.”
Dawson and Spiegelman have filed for patents on the use of irisin in PD. “If irisin’s utility pans out, we could envision it being developed into a gene or recombinant protein therapy,” Dawson said.
Spiegelman has also created a biotechnology company, Aevum Therapeutics Inc., based in Boston, to develop irisin into treatments for neurodegenerative disease.
“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,” he said.