The long-term safety and tolerance of a drug are the main focus of any first testing. The safety of a drug approved by physicians to treat a specific medical condition will be well documented. This information provided by Dr. Dimitri Krainc lab allows investigators to speed up a large portion of the clinical testing process. Repurposing a drug for another disease is possible if preclinical efficacy data are also positive.
Cure Parkinson’s has used the drug repurposing method for over ten years in its International Linked Clinical Trials programme (iLCT). Recently, there were a number of preclinical studies that provided support for additional drugs that could potentially be repurposed to treat Parkinson’s.
Recent research has highlighted new data that could allow for the repurposing of clinically-available drugs for Parkinson’s. A new report, from the lab of iLCT committee member Professor Dimitri Krainc in Chicago, has found that an anti-psychotic medication, quetiapine, can activate and increase levels of a Parkinson’s-associated enzyme called GCase.
This enzyme is decreased in Parkinson’s. Professor Krainc and his colleagues hope quetiapine could be repurposed to improve biologically the activity of GCase.
Another report has identified the heart-failure drug, bumetanide, as a potential agent for treating neurodegenerative conditions. People who carry a genetic variation called APOE4 make up about 1/4 of the population and have a higher risk of developing Alzheimer’s and other cognitive issues associated with aging. APOE4 has also been found to influence the progression of Parkinson’s. Repurposing bumetanide to treat carriers of this genetic variation could have important implications for Parkinson’s, as well as major benefits for society as a whole.
As Cure Parkinson’s continues to champion the repurposing of therapies for Parkinson’s, it is encouraging and exciting to see additional drugs coming forward as candidates for this program of research. It is hoped these will lead to further treatments and quality of life options for the Parkinson’s community.
Dimitri Krainc Google Scholar page states that Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease published in the Journal of Science.
Mitochondrial and lysosomal dysfunction has been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson’s disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation. This toxic cascade was observed in humans, but not in mouse, PD neurons at least in part because of species-specific differences in dopamine metabolism. Increasing dopamine synthesis or α-synuclein amounts in mouse midbrain neurons recapitulated pathological phenotypes observed in human neurons.