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TRANSLATE

Tuesday, October 25, 2016

Insights into Rare Disease May Lead to Novel Therapeutic Targets for Parkinson’s

 OCTOBER 25, 2016 BY ALEXANDRA ANDERSSON, PHD IN NEWS.



The rare lysosomal storage disorder Krabbe’s disease is caused by an enzyme deficiency and has been found to have surprising similarities with neurodegenerative disorders, including Parkinson’s disease.
Establishing this connection can be a valuable tool for developing novel therapeutic targets and new biomarkers for identifying patients at risk for developing Parkinson’s.
Krabbe’s disease causes mental and motor deficits, which mostly affects infants that usually die before the age of 2. It is included in a group of approximately 50 rare inherited disorders called lysosomal storage diseases. Lysosomes are commonly referred to as the “recycling center” in the cells and break down unwanted matter through a group of enzymes.
Due to a gene mutation, patients with Krabbe’s disease are deficient in one of those enzymes, called galactosylceramidase (GALC) — a compound of myelin — leading to damage of the protective myelin sheath that surrounds nerve cells and usually helps them communicate. This process causes severe motor impairments, some of which have Parkinson-like characteristics.
“It’s already been established that mutations to lysosomal enzymes, as present in Gaucher disease, can be a strong genetic risk factor for Parkinson’s disease. In this commentary, we highlight recent evidence that suggests pathophysiological changes due to GALCmutations in Krabbe’s disease may also be related to the pathology of neurodegenerating diseases like Parkinson’s,” Dr. Michael Marshall, co-author of the study, said in a press release.
In Parkinson’s disease, the protein alpha-synuclein accumulates inside neurons forming inclusions called Lewy bodies, which spread through the brain in a certain pattern as the disease progress and cause a loss of neurons. Researchers recently have found the same pattern in a mouse model of Krabbe’s, and alpha-synuclein has been identified in the brains of patients with the disease.
The findings may be a link between the two diseases. Researchers suggest that mutations causing only mild GALC deficiency could be a contributing mechanism in the accumulation of alpha-synuclein seen in late-onset conditions, including Parkinson’s and Alzheimer’s disease.
There is no cure yet for Krabbe’s disease, but researchers are working on a wide variety of promising therapeutic strategies that would potentially benefit patients with neurodegenerative disorders whose condition is influenced by GALC deficiency.
“A connection between Krabbe’s disease and Parkinson’s would also open the door for powerful new biomarkers for identifying subsets of patients at risk for the development of Parkinson’s,” the authors wrote.
http://parkinsonsnewstoday.com/2016/10/25/insights-rare-disease-may-lead-novel-treatment-targets-parkinsons

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