My PD Story

Resisting Parkinson’s Disease through Restoring Mitochondria Recycling  

The ability of a cell to recycle its defective parts is crucial for it to remain healthy and functional. This is especially true for neurons, which have some of the most complex processes to manage in the body and little room for inefficiency. In certain forms of Parkinson’s disease (PD), proteins involved in those critical recycling processes are damaged, which is believed to cause affected neurons to break down over time.  

Daniel Finley, PhD, a recipient of a Parkinson’s Foundation Impact Award, believes that he and his co-investigator Elena Ziviani, PhD, have found a “backup” compound that could fill in and restore neurons’ recycling abilities. With sufficient research and experimentation, this compound could become a new treatment that slows or prevents PD progression. 

Cells require a consistent and efficient supply of energy to function properly. This is provided by mitochondria, cellular powerhouses that turn oxygen into renewable chemical energy. Over time, these powerhouses wear down and eventually need to be recycled so that new mitochondria can be made.  

A protein called Parkin plays a major role in defective mitochondria recycling, and PD-linked mutations have been discovered that cause Parkin to become nonfunctional (in fact, the name “Parkin” comes from its discovery through PD research). Without functional Parkin, defective mitochondria clog up neurons and lead to their degeneration. 

In summary, healthy neurons rely on their ability to recycle defective parts, but in Parkinson’s, mutations in the Parkin protein hinder this process, leading to degeneration. Drs. Finley and Ziviani have identified a potential alternative way to stimulate the recycling function, which can potentially lead to new treatments. 

Recent experiments conducted by Dr. Ziviani have revealed that a compound they discovered, called IU1, can enhance an alternative mitochondria recycling process in neurons with dysfunctional Parkin. Additional chemistry led to the discovery of an IU1 variant, called IU1-366, that works even better. Next, the lab will test how it works in mice to ensure its safety and effectiveness for future human trials. 

From his lab at Harvard Medical School in Boston, MA, Dr. Finley will first administer IU1-366 to mice and measure how that changes mitochondria upkeep in brain neurons.  

Then, he will use mice genetically modified to have dysfunctional Parkin, simulating PD, to see if IU1-366 can overcome the disease-related mitochondria recycling issues. Across all mouse experiments, Dr. Finley will also monitor how IU1-366 affects the animals’ general health, assessing whether the treatment has side effects.  

Finally, Dr. Ziviani will delve deeper into the biochemistry of IU1-366 using neurons in petri dishes, looking to better understand the mechanisms behind how the compound works to guide future therapeutic improvements. 

These studies will determine if IU1-366 could be a future treatment for people with Parkin-affected PD, opening a potential new option that may slow disease progression.  

Speaking on the merit of his upcoming research, Dr. Finley said, “With this award, we will be able to assess more deeply, using a mouse model, whether IU1-366, or a closely related compound, could have therapeutic benefit in humans. We are very excited to move this work forward and are hopeful for interesting results.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.