In breakthrough, Israeli researchers detect Parkinson’s markers 15 years before symptoms
Tel Aviv University-led team uses super-resolution microscopy to detect abnormal aggregates in skin cells, focusing on 2 gene mutations known to be widespread among Ashkenazi Jews
Reporter at The Times of Israel
For the first time, researchers at Tel Aviv University have developed a method to detect protein aggregation in cells that are the hallmark of Parkinson’s disease. This discovery might enable diagnosis up to 15 years before the first symptoms appear, facilitating early treatment or even preventing the currently incurable disease.
The researchers focused on 2 gene mutations known to be widespread among Ashkenazi Jews, said Prof. Uri Ashery and PhD student Ofir Sade of Tel Aviv University, who led the team of researchers from Israeli medical centers, Germany, and the United States.
“We hope that in coming years it will be possible to offer preventive treatments for family members of Parkinson’s patients who are at risk of developing the disease,” Ashery told The Times of Israel.
Using super-resolution microscopy, the researchers examined Parkinson patients’ cells — not from their brains, but from their skin.
The study was published this month in the peer-reviewed scientific journal Frontiers in Molecular Neuroscience.
Parkinson’s disease
According to the World Health Organization (WHO), Parkinson’s disease is a brain condition that causes painful muscle contractions, tremors, and difficulty speaking.
The prevalence of Parkinson’s has doubled in the past 25 years. There are about 8.5 million people with the disease worldwide, and 1,200 new sufferers are diagnosed annually in Israel.
Ashery said that Parkinson’s is characterized by the destruction of neurons that produce dopamine in the midbrain’s substantia nigra area.
By the time the motor symptoms of Parkinson’s appear, from 50 to 80% of these dopaminergic neurons are already dead, and there isn’t a way to revive them.
Current treatments, therefore, are “quite limited,” Ashery said, because the patient is already in a “relatively advanced stage of the disease.”
‘Very big chunks’
The specific protein that the researchers studied, the alpha-synuclein protein, usually works as a single protein or what’s known as a tetramer, a protein with 4 subunits.
“But it needs a few other fellows, maybe 2 to 4,” to do its job of regulating the cell, Ashery said.
If there is a mutation, the protein starts to create what’s known as an aggregation, or binding. Instead of a few others, it binds “thousands of these nucleons” together, Ashery explained.
This abnormal aggregation is a hallmark of Parkinson’s.
“When you look at the brain of a person who died from Parkinson’s,” he said, “you will see very big chunks of abnormal aggregations of the protein.”
Sadeh said that if researchers can identify the process at an early stage, “we might be able to prevent further protein aggregation and cell death.”
Looking under the skin
Scientists are all “looking for the cell aggregates,” Ashery said, but they “don’t want to take biopsies of people from their brains.”
Ashery said they decided to take a biopsy from the skin because “the alpha-synuclein protein is found in every nerve cell, not only in the brain but also in nerve cells in the sweat gland and hair follicles.”
The researchers took skin biopsies from seven people with Parkinson’s and seven people without the disease.
“To see the aggregation, we used super-resolution microscopy that allows us to see a single molecule or an aggregate of molecules,” he said.
Sadeh said that the team examined the samples with the unique microscope, applying an innovative technique called super-resolution imaging.
Combined with advanced computational analysis, the team was able to map the aggregates and distribution of alpha-synuclein molecules.
Early detection
After doing an initial study on the brains of mice, Ashery said they found “a very nice correlation” between the progression of Parkinson’s and the aggregation of the protein in the brain.
They used an inhibitor to stop the aggregation, finding “treatment relief.”
A clinical trial is now underway to test this inhibitor on humans with the hope that it hinders the formation of the aggregates that cause Parkinson’s disease.
With the study’s proof of concept, the researchers now plan to expand their work with support from the Michael J. Fox Foundation for Parkinson’s Research.
In Israel, Ashery said, there is a large community of Ashkenazi Jews who have a lot of gene mutations that increase the risk for Parkinson’s and other diseases.
The goal is to look at younger Ashkenazi Jews who might have this genetic mutation even if they don’t yet have symptoms.
“We hope that in coming years, it will be possible to offer preventive treatments and early diagnosis of Parkinson’s as well as other neurodegenerative diseases, including Alzheimer’s,” Ashery said.
