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Scientific interpretation:

The rationale behind UDCA for Parkinson’s disease modification

Original article: Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease, Brain: 2013. 

The takeaway

Using a comprehensive screening approach, the disease modifying potential of 2000 compounds was tested. By addressing their potential to rescue mitochondrial function, researchers identified a family of compounds related to bile acids, one of which is UDCA.

Why is it important?

UDCA is an FDA approved liver drug. Testing its potential for disease modification in Parkinson’s is therefore that much more feasible and has been prioritized by the Linked Clinical Trials programme.


Efforts to discover disease modifying therapies for Parkinson’s often focus on assessing how good a given compound is at rescuing neurons which have been damaged with a particular toxin. But compounds can fail to get through this important stage, for a number of reasons which don’t necessarily reflect their true disease modifying potential.

To get around difficulties with this method, the Sheffield-based team took a different approach. Rather than look at whether a compound could reverse damage caused by a toxin (which in fact rarely resembles the effects of Parkinson’s), they looked at measures of mitochondrial function. It has long been known that mitochondria, the power houses of neuronal cells, begin to fail in Parkinson’s and limit cell survival. Therefore, compounds with disease modifying potential could be identified on the basis of their ability to reverse mitochondrial problems.

The details

The researchers used a type of skin cell donated by 2 people with Parkinson’s who had an identified mutation in the parkin gene – mitochondria in these skin cells show similar function to that seen in neurons. Using these cells, they screened an entire, 2,000 strong compound library, taking readings of mitochondrial function after treatment with each of these. This process gave 60 positive hits.

These were then tested for their toxicity and important drug-related characteristics, leaving 49 candidates to be taken through to the next stage: at this point, skin cells from 2 people with Parkinson’s and 2 controls were treated with each of these compounds at different doses, and their ability to produce energy was measured. This left 29 viable candidates, which were tested again on skin cells donated by a further 2 patients and controls, narrowing these down to 15, which were researched in terms of previous findings in the literature and their feasibility for use in trials. THis left 2 candidates, ursocholanic acid and DUA, belonging to the family of bile acids – substances produced naturally bt the body and found in bile. However, neither of these are FDA approved drugs.

Interestingly, the chemically related compound called UDCA is safe and in use for the treatment of a type of autoimmune liver disease for almost 30 years. The researchers replicated their findings with ursocholanic acid, as well as UDCA, in Parkin-deficient mouse neurons. They also replicated UDCA’s mitochondrial rescue effect in skin cells from 3 people with Parkinson’s who were carrying a LRRK2 mutation, known to cause a familial form the condition.

Next steps

A clinical trials of UDCA is running in Sheffield, UK and currently recruiting participants.

Related work

Original article: Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease, Brain: 2013. 


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