CMU and UBC teams find potential Parkinson’s treatment

By Eshaan Joshi

Familial Parkinson’s is a horrifying disease. It’s similar to Alzheimer’s and dementia in its ability to destroy a patient — removing their ability to function properly, and isolating them from the life they used to lead.

It’s no wonder those three diseases, along with cancer, have remained the focus of treatment development for decades. We as a species want to claw back what we can in regards to our lives, and we continue to fight back even against things we can’t control.

Except, recently, Carnegie Mellon and the University of British Columbia (UBC) have put together research revealing several molecules that can inhibit Leucine-rich repeat kinase 2 (LRRK2), the most common genetic cause of Parkinson’s disease. Teams of researchers from both Carnegie Mellon and UBC took on a Drug Discovery Challenge, trying to harness new computational methods to find binding agents that can attach to and inhibit the WD40 repeat (WDR) domain of LRRK2. Being able to do that is exceptionally difficult — there are no known inhibitors of WD40, and finding tiny molecules that do exactly the sort of thing necessary to get other tiny molecules to stick to them is a notoriously difficult task. But the teams at Carnegie Mellon and UBC managed to pull it off.

Using artificial intelligence to improve and further progress their development, they were able to narrow down the many billions of molecules they were initially inspecting to a very small selection. This was a narrowing of several orders of magnitude, from four-and-a-half billion molecules to only about 800, a more feasible amount that could be tested experimentally in a lab. Using the Pittsburgh Supercomputing Center, a center used for computation-heavy research, the molecules were simulated in short order, narrowing the results to 76 molecules with which they could move forward. By further investigating the molecules, they took the two most promising molecules that could inhibit LRRK2 and submitted the best analogs to the organizers of the challenge.

Thanks to their novel methods and impressive findings, Carnegie Mellon and UBC tied for first place in the drug discovery challenge. While this work is most certainly significant and will propel research in the right direction, it is only the beginning. There is a lot more work to be done regarding developing a possible treatment for Parkinson’s, but hopefully the methods employed by the Carnegie Mellon and UBC teams can expedite the research process.