Click the play button for the audio version of this Research Summary
Deep phenotyping of skin cells in Parkinson’s
Original article: Deep phenotyping of peripheral tissue facilitates mechanistic disease stratification in sporadic Parkinson’s disease. Prog Neurobiol 2020
Skin cells have been used to characterize specific cellular problems in people with Parkinson’s, in a new approach that may help match them to particular drugs that may work best for them.
Why is it important?
It is part a new approach to characterizing Parkinson’s and personalized medicine, not just in terms of overt symptoms but also on the basis of biological markers at the cellular level.
- Novelty 70% 70%
- Proximity 70% 70%
- Deliverability 70% 70%
Personalized medicine is a major goal for the future treatment of medical conditions. Tailoring therapies to each individual will have important benefits not only for the well being of the affected individuals, but also for society as a whole. This study is a first step in that direction. It is also an interesting study from the stand point of UDCA – a gallbladder treatment being repurposed for Parkinson’s by The Cure Parkinson’s Trust. The results of this new study provides further support for the ongoing clinical trial.
One of the most important hurdles in developing disease modifying treatments for people with Parkinson’s is that the condition manifests in different ways. Because of these differences in its symptoms, onset, and progression, research is increasingly focusing on identifying features that might predict which drug may benefit each individual best. This is personalized medicine, an approach to understanding and treating disease as it manifests in the person, rather than on average.
The rationale for this study was based on this idea. Teams in Sheffield and Oxford joined forces to attempt to subtype people with Parkinson’s depending on two major kinds of cellular problem, already identified as causing damage to neurons. One is energy production (which involves mitochondria, the powerhouses of the cell), and the other refers to lysosomes (which are responsible for efficient waste disposal inside the cell). This distinction is thought to be important because different kinds of cellular dysfunction have different effects, which will respond to different drugs.
The researchers concentrated on characterizing each participant in this study according to what they call their “deep phenotype”. The phenotype is the collection of measurable characteristics of the organism (such as blue eye colour), but in this case it is referred to as deep because it focuses additionally on the characteristics of individual cells.
They took small samples of skin cells from 100 people with Parkinson’s, and 50 healthy control individuals of the same age. A series of in-depth laboratory tests performed on these cells allowed the researchers to identify two subgroups, which showed the most pronounced energy production and waste disposal deficits. Some of these cells were then cultured into neurons, which eventually showed the same problems, and confirmed the utility of this approach in categorizing individuals with Parkinson’s as having a particular kind of cellular deficit, target through different treatments. UDCA (see linked summaries below), a drug that is normally used to treat liver and gallbladder disease and which is now being repurposed for Parkinson’s in work supported by The Cure Parkinson’s Trust. In this new cell culture study, UDCA was shown to restore mitochondrial function in cells that showed pronounced and even milder dysfunction. This result further bolsters the rationale for the UDCA clinical trial, and speaks for itself as a new way of predicting response to treatment.
A larger study replicating these findings in conjunction with trial data will be helpful in supporting this approach to identifying the right candidates for new potentially disease modifying therapies.
Related work and trials
UDCA trial in Sheffield, UK, now recruiting:
US Minnesota trial
Carling, P. J., Mortiboys, H., Green, C., Mihaylov, S., Sandor, C., Schwartzentruber, A., . . . Bandmann, O. (2020). Deep phenotyping of peripheral tissue facilitates mechanistic disease stratification in sporadic Parkinson’s disease