Scientists at New York University Abu Dhabi have helped to develop a molecule that may prevent patients with Parkinson’s disease from deteriorating.
While trials in people have yet to happen, tests on tissue samples and in mice indicate that the substance combats the formation protein accumulations in the brain linked to the disease.
If effective in patients, the molecule SK-129 would represent a major step forwards, because currently doctors focus on treating Parkinson’s symptoms rather than dealing with the underlying disease.
“You always hope to come across something that gives you good results, but this does on so many levels,” said Dr Mazin Magzoub, an associate professor at NYU Abu Dhabi, who leads a research group involved in the work.
“We were getting very promising results as to its potential to prevent or stop the aggregation of this protein.
“In a lot of these diseases, none of them really have a therapy. A lot of things are done for management rather than for treatment.”
Dr Magzoub and his team in Abu Dhabi collaborated with the laboratory of Dr Sunil Kumar, an associate professor at the University of Denver’s Knoebel Institute for Healthy Ageing.
The Denver scientists synthesised the artificial molecule alongside hundreds of others.
They tested them on human cells and on tissue from patients to identify those that might combat the accumulation of the protein alpha-synuclein.
Aggregations of this in the brain, called Lewy bodies, are associated with Parkinson’s and related neurodegenerative disorders.
About a dozen of the chemical substances were sent to the researchers in Abu Dhabi for further tests.
SK-129 was highlighted as being the most promising. Like the other molecules, it is a foldamer, an artificial molecule that folds to mimic the structure of proteins.
Healthcare breakthrough
When tested in mice genetically engineered to develop symptoms similar to those of Parkinson’s, SK-129 was found to slow deterioration.
It also proved effective in mice that had samples from a diseased brain injected into them to speed up the disease’s development.
Dr Magzoub said that mice treated with SK-129 had “far fewer” protein aggregates in their brain than mice that had not been treated.
As well as Parkinson’s, other diseases that SK-129 may be effective against include Lewy body dementia and multiple system atrophy.
A key finding of the work is that the protein passes from the blood into the brain.
The blood-brain barrier prevents potentially harmful substances from getting into the brain, but if SK-129 is to be effective, it has to pass through.
“The nice thing about this molecule, as we tested it, we showed that it works well in cells and even in the brain, so it crosses the blood-brain barrier efficiently, and then prevents this protein alpha-synuclein from aggregating, thereby preventing the onset and development of Parkinson’s symptoms,” Dr Magzoub said.
The scientists found that the molecule also prevented the aggregation of proteins in a roundworm with the scientific name Caenorhabditis elegans, a species commonly used in studies.
The findings, the culmination of several years of work, have been released this month [April] in a study in Science Translational Medicine.
In Parkinson’s patients, changes in the brain cause deficiencies of the neurotransmitter dopamine in certain brain structures, resulting in physical symptoms, such as tremors and other problems, including sleep disorders and cognitive changes.
Making progress
While the results are promising, use of the molecule to treat Parkinson’s disease or related conditions in people is a number of years away, should it happen.
The molecule has been patented and Dr Magzoub said that there had been interest from a biotechnology company in licensing it.
Further refinement of the molecule, involving alterations to its structure to optimise the way it interacts with proteins associated with Parkinson’s, and further tests, including clinical trials, would be necessary before its commercial release.
“Hopefully with a second generation [molecule], we’d have potentially even more interest, once we develop and optimise it further,” he said.
“As university labs, we are well equipped and we do these extensive preclinical trials, but when it comes to then taking it to the next step, the clinical trials, this is where a big partner, a pharma or biotech company, would come in and … see whether it has potential in humans … The threshold for making it through clinical trials is very high.”
The hope is that, ultimately, other molecules developed in a similar way could even reverse the accumulation of proteins, which could lessen symptoms rather than simply stop them from getting worse.
Dr Ummulkiram, a specialist neurologist at Aster Hospital Muhaisnah in Dubai, described the development of SK-129 as “a promising step towards disease-modifying therapies in Parkinson’s disease”.
“By targeting the aggregation and spread of pathogenic proteins, processes believed to drive neurodegeneration, this approach goes beyond symptomatic relief and addresses a core mechanism of disease progression,” she said.
She said it was “particularly encouraging” that the molecule crossed the blood-brain barrier and was effective in different tests.
“While these findings are still preclinical, they highlight a potentially important direction for future therapeutic development,” she added.
