PARP inhibitors for ALS? Penn researchers post promising finds in brain disease

As a cancer drug, PARP inhibitors have inspired blockbuster projections for drugmakers like AstraZeneca and Pfizer. What if they can also treat brain diseases?

Leeanne McGurk

A team of researchers at the University of Pennsylvania are trying to answer that question, having found that aside from stopping tumor cells from repairing damaged DNA, PARP inhibitors can also reduce the amount of a harmful structure that’s associated with amyotrophic lateral sclerosis — known as ALS or Lou Gehrig’s disease — and some forms of frontotemporal degeneration (FTD).

The key here, according to their paper in Molecular Cell, is the interaction between the PAR molecule and a protein dubbed TDP-43. When TDP-43 is out of place, it sometimes binds with PAR, eventually forming a harmful structure called stress granules.

When the researchers performed tests on cultured cells, however, they observed that the PARP inhibitors could “alleviate the buildup of TDP-43 that mirrors the abnormal protein clumps we see in disease,” said lead author Leeanne McGurk, a research associate in Penn biology professor Nancy Bonini’s lab. Bonini led the study with colleague James Shorter.

AstraZeneca has been aggressively pursuing new indications for Lynparza, its first-in-class PARP star now approved for breast and ovarian cancers. Rivals including Tesaro, Clovis and Pfizer are coming up close in an increasingly crowded race, and that’s not to mention newer players like China’s Impact and UK’s Artios, run by a pair of Lynparza vets.

This preliminary scientific finding could well affect all of them.

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VP Oncology Biology
Skyhawk Therapeutics Waltham, MA
Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT

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