In a new study, researchers have used patient-derived neurons to develop and test a new strategy to treat Parkinson’s disease by mitigating the effects of harmful genetic mutations.
The research was conducted by Northwestern Medicine scientists.
Parkinson’s is the second-most common neurodegenerative disorder, predominately affecting neurons in an area of the brain called the substantia nigra.
These neurons are responsible for producing dopamine—a chemical messenger used to transmit signals throughout the brain—and for relaying messages that plan and control body movement.
Some experimental treatments for genetic disorders target mutated proteins or enzymes, but this study took a different approach.
Instead of trying to fix broken enzymes, the scientists amplified healthy ones, an approach that successfully alleviated symptoms of Parkinson’s disease in human brain cells and in mouse models.
According to the team, mutations in the gene GBA1 represent the most common genetic risk factor for Parkinson’s disease, and GBA1 codes for an enzyme called glucocerebrosidase (GCase) that is important for neuronal function.
Parkinson’s disease -associated mutations can disable GBA1 and produce misshapen GCase enzymes, which contribute to an accumulation of toxic proteins in dopamine-producing neurons.
As this neuronal population dies, patients experience symptoms such as tremors and slowness of movement.
While some medications can offer relief for these symptoms, there is no treatment that can stop or slow the disease.
Drug development for patients with GBA1-linked Parkinson’s has largely focused on stabilizing mutated GCase and limiting its harmful effects.
However, these treatments would be effective only in a few types of Parkinson’s disease.
This study highlights targeting wild-type GCase activation as a treatment for multiple forms of Parkinson’s disease.
The team further emphasizes the value of patient-derived neurons for drug development in Parkinson’s disease.
The lead author of the study is Dr. Dimitri Krainc.
The study is published in Science Translational Medicine.
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