A new approach combining AI and genetics could be used to identify the risk factors of Parkinson’s, and drugs that could potentially be repurposed to treat the condition, scientists say.
Researchers have created an advanced AI-meets-genetics model described as “systems biology” which uses AI to integrate and analyse a range of info, including genetic, proteomic, pharmaceutical and patient datasets.
This enables the identification of patterns that may not be obvious from analysing one form of data on its own.
The work, at the Cleveland Clinic Genome Center (CCGC), could also help to find FDA-approved drugs that could potentially be repurposed for Parkinson’s treatment.
Making compounds that halt or reverse the progression of Parkinson’s disease is especially challenging because the field is still identifying which genes cause which Parkinson’s disease symptoms when mutated.
First author Lijun Dou says: “Many of the known genetic mutations associated with Parkinson’s disease are in non-coding regions of our DNA, and not in actual genes.
“We know that variants in noncoding regions can in turn impact the function of different genes, but we don’t know which genes are impacted in Parkinson’s disease.”
Using their integrative AI model, the researchers were able to cross-reference genetic variants associated with Parkinson’s disease with multiple brain-specific DNA and gene expression databases.
This allowed them to infer which, if any, specific genes in the brain are affected by variants in noncoding regions of our DNA.
The team then combined the findings with protein and interactome datasets to determine which of the genes they identified affect other proteins in our brains when mutated.
They found several potential risk genes (such as SNCA and LRRK2), many of which are known to cause inflammation in our brains when dysregulated.
The researchers then asked whether any drugs on the market could be repurposed to target the identified genes. Even after successful drugs are discovered and made, it can take an average of 15 years of rigorous safety testing for the medication to be approved.
Study lead and CCGC director Feixiong Cheng says: “Individuals currently living with Parkinson’s disease can’t afford to wait that long for new options as their conditions continue to progress.
“If we can use drugs that are already FDA-approved and repurpose them for Parkinson’s disease we can significantly reduce the amount of time until we can give patients more options.”
By integrating their genetic findings with available pharmaceutical databases, the team found multiple candidate drugs. They then referenced electronic health records to see if there were any differences in Parkinson’s disease diagnoses for patients who take the identified drugs.
For example, individuals who had been prescribed the cholesterol-lowering drug simvastatin were less likely to receive Parkinson’s disease diagnoses in their lifetime.
Dr. Cheng says the next step is to test simvastatin’s potential to treat the disease in the lab, along with several immunosuppressive and anti-anxiety medications that warranted further study.
