Nitrase, HitGen Join to Discover Potential of Nitrase Enzymes

Current Parkinson's research shows synuclein nitrase lowers alpha-synuclein

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Nitrase Therapeutics has partnered with HitGen in the search for novel therapies that suppress nitrases, a class of enzymes discovered by Nitrase.

Nitrases are responsible for nitration, a type of biochemical modification of proteins that is linked to cellular stress and can change that protein’s structure, function, and localization.

These enzymes have been implicated in the development of Parkinson’s disease and other neurodegenerative diseases, as well as in cancer, and respiratory and fibrotic (tissue scarring) diseases. As such, blocking their activity may have several therapeutic applications.

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Blocking synuclein nitrase to ease alpha-synuclein clumping in nerve cells

Data presented by Nitrase earlier this year showed that blocking a type of nitrase, called synuclein nitrase, lowered toxic alpha-synuclein protein levels in neurons derived from Parkinson’s patients. It also restored these nerve cells’ electrical activity.

The buildup of toxic alpha-synuclein clumps is implicated in the progressive death of specific neurons in people with Parkinson’s.

“Nitrase Therapeutics has made breakthrough discoveries in the role of protein nitration, caused by company-discovered enzymes called nitrases, in various diseases,” Pierre Beaurang, PhD, CEO of Nitrase Therapeutics, said in a press release.

“We have identified over 30 nitrases thus far, and we look forward to working with HitGen to expand our existing pipeline of compounds that are capable of modulating nitration,” potentially leading to treatments, Beaurang added.

Under the collaboration, HitGen will apply its DNA-encoded library (DEL) technology with the aim of designing, generating, and screening compounds that are able to modulate the activity of nitrase enzymes that are of interest to Nitrase.

DEL is a recent advancement in drug discovery technology where small molecules are attached to a DNA “barcode.” This short piece of DNA contains the instructions for making a small molecule. This way, when testing several of these potential therapies simultaneously, the researchers can easily identify those binding to its target through their “barcodes.”

The DEL technology can be applied to rapidly make and test a large number of potential therapies in comparatively short and simple experiments, HitGen reports.

“DEL is an efficient ‘engine’ to advance drug discovery,” said Jin Li, PhD, chairman of the board and CEO at HitGen.

“We look forward to working closely with Nitrase’s scientists to identify novel hits from HitGen’s DNA-encoded libraries and generate new lead compounds for their research programs to address unmet medical needs associated with Parkinson’s and other diseases,” Li added.

Under the terms of the agreement, Nitrase will give HitGen an upfront payment, with the potential for additional payments if certain milestones are met. Payment amounts were not disclosed.

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