First DUB Enzymes Identified by Partnership as Potential Therapeutic Targets for Parkinson’s and Alzheimer’s

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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dopamine and Parkinson's

Mission Therapeutics and AbbVie have identified several molecules, called deubiquitylating enzymes, or DUBs, that may be potential therapeutic targets to treat Parkinson’s and Alzheimer’s diseases.

This comes after the two companies announced a collaboration last year to identify DUB inhibitors to treat these neurodegenerative disorders. Identifying potential targetable DUBs is the first step in developing specific inhibitors.

In Parkinson’s disease, a protein known as alpha-synuclein becomes misfolded and forms toxic aggregates or clumps within nerve cells. These toxic aggregates result in the death of dopaminergic neurons, those that produce the neurotransmitter dopamine. Neurotransmitters are chemical substances produced in response to nerve signals that act as messengers.

DUBs are a large family of enzymes that help regulate protein degradation. Some of these enzymes help maintain neuronal health by regulating the destruction of misfolded and potentially toxic proteins.

Therapies that modulate the activity of specific DUBs in the brain may regulate the degradation of toxic proteins and therefore be used to treat neurodegenerative diseases, such as Parkinson’s.

Although DUBs represent an attractive therapeutic target for several disorders, development of potent inhibitors suitable for clinical use has been a challenge due to issues linked to lack of specificity and selectivity.

Mission Therapeutic’s discovery platform aims to overcome these limitations by identifying small molecule inhibitors that could function in the brain. The panel of DUBs identified as potential therapeutic targets will now be further characterized.

“The numbers of people living with Alzheimer’s and Parkinson’s is growing and there are currently no treatments capable of stopping or reversing either disease’s progression,” Eric Karran, vice president of Discovery Neuroscience Research at AbbVie, said in a press release. “This collaboration, using Mission’s DUB technology platform, shows promise for identifying potential drug targets and the development of new therapeutic options. We look forward to advancing our drug discovery programs with our Mission colleagues.”

The collaboration between the two companies has been short-listed for Scrip’s 2019 Best Partnership Alliance Award, which seeks to reward pharmaceutical and/or biotech companies working together to develop new medicines.

“Partnering with AbbVie has been a great experience and instrumental for our research. AbbVie brings expertise and capabilities complementary to our own, and it is a testament to all involved that we have reached this important milestone,” said Anker Lundemose, Mission’s CEO.

“We have made good progress to-date and our high-quality data has enabled AbbVie to take the decision to select multiple DUBs for further investigation. We look forward to continuing to work together to discover and develop DUB inhibitors towards the treatment of Alzheimer’s and Parkinson’s diseases,” Lundemose added.

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