Researchers at Tel Aviv University, together with colleagues from the UK and Germany, said they have found biomarkers in mice that help detect the buildup of a protein that is linked to the development of Parkinson’s disease.
The discovery could enable early detection and treatment, helping potentially to “significantly delay” the progression of the debilitating illness, the researchers said.
Parkinson’s disease is a debilitating neurodegenerative disease affecting everything from speech, posture and gait to digestion, sleep, impulse control and cognition. Current treatments are able to alleviate some symptoms, but there is still no cure for the disease, which affects close to a million Americans and 10 million people worldwide.
By the time a patient is diagnosed with Parkinson’s disease, 50 percent to 80 percent of the cells in the part of the brain called substantia nigra — which is responsible for coordinating movement — are already dead, possibly due to development of toxicity as result of the build-up — or aggregation — of the alpha-synuclein protein, a hallmark of the disease.
Studying samples from the brains of mice affected by the disease, the researchers used super resolution microscopy and analysis to find “new biomarkers” associated with the progression of the disease, said Prof. Uri Ashery, head of the Sagol School of Neuroscience and from the George S. Wise Faculty of Life Sciences at Tel Aviv University who co-authored the report.
These “biomarkers” are very early stages in the accumulation of the protein, he explained, something that was not detectable before, via regular microscopes “and this therefore can allow starting treatment at early stages of the disease.”
The study was published on June 5 the journal Acta Neuropathologica.
“Together with our collaborators at Cambridge University, who developed a special mouse model for Parkinson’s disease, we were able to detect different stages of the aggregation of this protein,” Ashery said in a statement. “We correlated the aggregation with the deteriorating loss of neuronal activity and deficits in the behaviour of the mice.”
The findings are “extremely important,” said co-author Dr. Dana Bar-On of the Sagol School of Neuroscience, because if the buildup of the protein can be detected at an early stage, physicians will be able to monitor the effects of drugs on this aggregation. “We hope that this research can be implemented for use in the early diagnosis of Parkinson’s in patients.”
In a phone interview, Ashery said the researchers then administered to diseased mice a new drug developed at the Max Planck Institute in Gottingen and the Ludwig Maximilian University of Munich, which is able to inhibit the aggregation of this protein. After these mice were treated with this drug for a few months, there was a “very significant” improvement in their pathology, he said.
The motoric behavior in the sick mice “was reversed,” he said, and the levels of dopamine, a transmitter involved in fine tuning an organism’s movement that is low in Parkinson’s patients, recovered.
There was a “recovery of motor disabilities,” he said.
After the treatment, when the researchers looked at the biomarkers in the sick mice, they saw that they had managed to get “rid of the toxic aggregate. We reduced the abundance of the dense aggregate.”
“This is a significant step forward in the world of Parkinson’s research,” he added.
The next step, said Ashery, is to try to detect these biomarkers in a noninvasive manner in human patients with Parkinson’s disease and in their family members.
“By detecting aggregates using minimally invasive methods in relatives of Parkinson’s disease patients, we can provide early detection and intervention and the opportunity to track and treat the disease before symptoms are even detected,” he said.
The idea is to “detect the disease early and non-invasively without needing to make samples from the brain to find the biomarkers. We want to be able to detect these aggregates maybe in the skin or in the blood or other fluids.”
The feasibility of that depends on “the amount of investment” that will now be put into the matter, he said.
“But it is possible, it is feasible,” he added. “You need a good collaboration with hospitals to get access to tissue samples from patients and then you can do it.”