Thursday, September 4, 2014

Applications: Screening for Parkinson's disease treatments

Parkinson’s disease is the second most common neurodegenerative disease that affects 7 million people worldwide. It is an incurable, progressive disease with treatments currently restricted to symptom reduction, with debatable efficacy.

TEM image of mammalian lung showing mitochondria
by Louisa Howard
One of the potential causes of the disease is poorly functioning mitochondria in the neurons of affected
individuals. A recent study has also shown that mitochondria are also abnormal in the skin cells of patients. This observation was used to test skin cells derived from Parkinson’s sufferers for potential drugs that can restore mitochondrial function.  Previous compound screens have typically used toxin induced models of Parkinson’s in unaffected cell lines. The authors adopted the approach that even though their model uses skin cells, as they are patient derived they will be more physiologically relevant.

As a proof of principle, patient fibroblasts were treated with 2000 small molecules, and the effect on their mitochondrial membrane potential was measured using a BMG LABTECH FLUOstar Omega plate reader. After performing confirmation experiments, including checking the efficacy on cells from different patients, 15 compounds were found to have a significant effect on  mitochondria. Of these, 2 were taken for further study and were shown to be effective in models of inherited Parkinson’s disease as well as with neuronal models of the disease.

This paper proposes a very interesting method of screening for compounds with efficacy in cells of individuals affected by Parkinson’s in order to relatively cheaply identify compounds worthy of more extensive, neuron focused investigation.

Original article: 
  • H. Mortiboys
  • J. Aasly
  • and O. Bandmann 
  • Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease Brain (2013) 136 (10): 3038-3050