AI Identifies a Potential Drug for Parkinson's

Artificial intelligence has recently gotten a bad reputation, and for good reason. The release of OpenAI's ChatGPT has sparked fear that it would replace all forms of writing. Nevertheless, news outlets stated that Bing's new AI-powered search engine had done everything from threatening users to falling in love with them. Nonetheless, there are still AI applications that unquestionably benefit the planet. Take, for example, researchers who employed artificial intelligence to uncover a potential new Parkinson's disease treatment. At least five genes implicated in Parkinson's disease are associated with defective mitophagy, either directly or indirectly, so the researchers investigated substances that could improve the mitophagy process.

Drug in Test

Many similar compounds have been found; however, the majority of them cause cell damage, ruling them out as therapeutic options. This prompted the scientists to wonder if the literature describing these compounds could lead them to other compounds, ones that had not previously been connected to mitophagy enhancement but were characterized using phrases that also appeared in articles discussing the known enhancers.

One of the primary skills of IBM Watson for Drug Discovery, an AI program run on a supercomputer that examines published literature for patterns of important words, sentences, and juxtapositions, is identifying patterns of such semantic similarity.

The researchers utilized the algorithm to create a semantic "fingerprint" of genuine mitophagy enhancers, and then searched the literature for similar fingerprints on a collection of over three thousand candidates from a pharmacological database.

In cell culture, the top 79 candidates were tested against a mitochondrial toxin. The top three choices from that assay were then examined on multiple different mitophagy assays, and probucol, a cholesterol-lowering medication, was found to have the best combination of effectiveness and likely safety.

In two separate animal models of Parkinson's disease (PD), probucol was reported to enhance motor function, survival, and neuron loss (PD is primarily a movement disorder).

The effect of probucol on mitophagy was dependent on the production and function of lipid droplets, which are transient cell structures that help maintain mitochondrial integrity during stress and accumulate abnormally in Parkinson's disease.

Mystery Around Probucol

Probucol is known to target ABCA1, a lipid transport protein, and lowering ABCA1 levels lowered Probucol's ability to induce mitophagy, implying that ABCA1 is a plausible mediator of the involvement of lipid droplets in mitophagy (1^✔ ✔Trusted Source
Probucol: pharmacology and clinical application

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"Our study demonstrated a dual in silico/cell-based screening methodology that discovered known and novel mitophagy-enhancing mechanisms," McQuibban added.

"Given the linkage between lipid droplet accumulation and ABCA1, it seems likely that Probucol enhances mitophagy through mobilization of lipid droplets. Targeting this mechanism may be advantageous."

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McQuibban adds, "In our study, we used the AI platform IBM Watson to efficiently identify currently approved drugs that could potentially be repurposed as therapies for Parkinson’s disease."

Reference:

1. Probucol: pharmacology and clinical application - (https://pubmed.ncbi.nlm.nih.gov/2406299/)

Source-Medindia