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Friday, March 22, 2019

Grant Will Enable Pharmacologist to Expand Gaucher Disease Research to Parkinson’s

 MARCH 22, 2019     BY MARY CHAPMAN 




As it sometimes happens in rare-disease research, a prospective therapy for one disorder has potential to help another. So it is that, at Temple University, molecular pharmacologist Marlene Jacobson, PhD, has been awarded a joint grant to explore how a discovery could affect Parkinson’s disease (PD) patients.
Specifically, The Michael J. Fox Foundation (MJFF) and The Silverstein Foundation for Parkinson’s with GBA want Jacobson to further study compounds that she found could reverse Gaucher disease Type 2, the most severe form of the lysosomal storage disorder caused by deficiencies in the glucocerbrosidase (GCase) protein due to mutations in the GBA1 gene. 
Some 10 percent of PD patients carry the same mutation, making it the most common genetic disease risk. GCase allows brain cells to clear debris via lysosomes, which are special compartments within cells that digest and recycle different types of molecules. Patients with reductions in GCase activity can’t effectively remove debris, which scientists widely hypothesize is toxic to brain cells.
“I came to Temple because I wanted to make a difference in patients’ lives,” said Jacobson in a press release. “I wanted to use my drug discovery skills and apply them to help patients who are underserved.”
An associate professor of pharmacodynamics in Temple’s Department of Pharmaceutical Sciences, and associate director of its Moulder Center for Drug Discovery Research, Jacobson will expand her Gaucher research to include PD patient cells that have the GBA1 mutation. She joined Temple six years ago after 24 years in research and drug discovery for Merck Research Laboratories.
”The key is we have the full disease environment in the cell,” said Jacobson. “We’re very fortunate to have access to these patient cells, and we treat them with respect as they provide an advantage in demonstrating a compound’s potential to reverse a disease state.”
Parkinson’s patients with the GBA mutation develop the disease at an earlier age, she said, and their cognition symptoms are worse relative to patients without the mutation.
”The link between mutations in Gaucher disease and Parkinson’s disease suggests a common disrupted mechanism or pathway. We can translate the compounds we have found to improve Gaucher and Parkinson’s.”
Currently, there is no effective treatment for Gaucher disease Type 2. In Parkinson’s, available therapies are focused on raising dopamine levels in patients’ brains, or on controlling the symptoms themselves.
“This work is so exciting and so primed for discovery,” Jacobson said, adding that the pharmaceutical industry is increasingly looking to academic investigators for breakthrough ideas leading to new treatments.
The amount of the grant was not disclosed.
The MJFF aims to find a cure for Parkinson’s through an aggressively funded research agenda, and to help develop improved therapies for current patients. The Silverstein Foundation is focused on finding ways to prevent the onset of Parkinson’s in GBA-mutation carriers.
https://parkinsonsnewstoday.com/2019/03/22/temple-pharmacologist-grant-expand-research-parkinsons/

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