Northwestern Medicine researchers, led by Dr. Dimitri Krainc, used patient-derived neurons to develop and test a novel strategy to treat Parkinson’s disease by mitigating the effects of harmful mutations. Taking a different approach, the Chicago-based group sought to amplify healthy enzymes, an approach that successfully alleviated symptoms of Parkinson’s disease (PD) in human brain cells and in mouse models! In an exciting move, Krainc has launched a startup venture to aggressively pursue commercialization.
The results were published in the October 16 edition of Science Translational Medicine.
‘Wild-Type GCase Activation: a Possible Translational Target
Dr. Krainc, chair of neurology and director of the Center for Neurogenetics at Northwestern University Feinberg School of Medicine commented that “This study highlights wild-type GCase activation as a potential therapeutic target for multiple forms of Parkinson’s disease.”
The second-most common neurodegenerative disorder, Parkinson’s disease (PD) predominantly affects 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.
The most common genetic risk factor for PD are mutations in the gene GBA1—and GBA1 codes for an enzyme called glucocerebrosidase (GCase) that is important for neuronal function. PD-associated mutations can disable GBA1 and produce misshapen GCase enzymes, which contribute to an accumulation of toxic proteins in dopamine-producing neurons.
Neuronal Death & No Cure
With neuronal population death comes patient symptoms such as tremors and slowness of movement. While some medications can offer for these symptoms, there is no treatment that can stop or slow the disease.
Krainc reports that most drug development for patients with GBA1-linked Parkinson’s has largely focused on stabilizing mutated GCase and limiting its harmful effects. However, these treatments are only effective in a few types of PD. The Chicago-team suggests that instead, by activating wild-type GCase may be more relevant for multiple forms of PD that exhibit the reduced activity of wild-type GCase suggests Dr. Dimitry Krainc.
The scientists developed a new series of chemical activators that stabilized and amplified normal GCase. The activator, a small molecule that binds to GCase, improved PD-related cellular dysfunction in patient-derived neurons. The Northwestern originated press release notes that these activators worked in several varieties of PD, evidencing the strategy may work for a wide range of patients.
Building on 2017 Research
Krainc led a study in 2017, published in Science, that found that some of the key pathological features of PD were only identified in human neurons and not in mouse models, leading him and the team to consider the value of patient-derived neurons for drug development in Parkinson’s disease.
Commercialization with Surmount Bio
Dr. Krainc has launched a Chicago-based startup venture called Surmount Bio which he will use to further develop GCase activators described in the study. Based in the Morton Medical Research Building, according to an SEC filing the venture already sold $6 million worth of stock to OrbiMed.
Call to Action: We think that Dr. Krainc could be on to something and it is definitely worth tracking his new venture called Surmount Bio.