What is UDCA and why is this a potential therapy for Parkinson's? 

UDCA, or Ursodeoxycholic Acid, is a bile acid which occurs naturally in the body and is secreted into the small intestine helping the body digest fats and, as the drug Ursidiol, is used to dissolve gallstones. Originally used to treat cirrhosis of the liver, researchers found that the rescue effect of UDCA on the liver cells may actually be due to cellular protective mechanisms rather than simply displacing the build up of bile acids. 

This drug has shown to have a marked rescue effect on the mitochondria or ‘cell batteries’ in Parkinson’s affected neuronal tissue. Researchers demonstrated that UDCA could protect dopamine cells grown in culture from apoptosis, or programmed cell death; and they also found that UDCA did this by regulating a specific cell 'survival pathway'(1). The neuroprotective effects of UDCA have also been found in a large screening study conducted by researchers at the University of Sheffield.(2)

Why do researchers think this drug has the potential to slow, stop or reverse Parkinson’s?

Mitochondrial dysfunction was first identified in the brains of people with Parkinson’s and is now universally accepted as a key PD causal factor. Neurons have particularly high energy demands so defects in their mitochondria will crucially affect their survival. The potential rescue of mitochondrial function is therefore widely perceived to be a promising therapeutic strategy in Parkinson’s. 

In certain genetic forms of Parkinson’s (such as those associated with mutations in the PARK2 gene), the mitochondria in cells becomes dysfunctional and may not be disposed of properly. When the researchers tested UDCA on PARK2 skin cells, and they found that the drug rescued the mitochondrial function in those cells. They next tested UDCA on skin cells from people with Parkinson’s who had mutations in the PARK8 (LRRK2) gene. And when they treated the PARK8 cells with UDCA, it rescued the mitochondrial effect in those cells(3).

Further research(4) has found that UDCA rescued a rodent model of Parkinson’s (involving the neurotoxin rotenone). UDCA not only improved mitochondrial performance here but also demonstrated anti-inflammatory and anti-cell death properties.

Given the extent of this research, CPT is keen to test UDCA in clinical trials for Parkinson’s and funding is being sought.

Sources:

1. https://www.ncbi.nlm.nih.gov/pubmed/22178905

2. https://www.ncbi.nlm.nih.gov/pubmed/24000005/

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560055/

4. https://www.ncbi.nlm.nih.gov/pubmed/25502462