PMN310 is a monoclonal antibody being developed by ProMIS Neurosciences as a possible treatment of Alzheimer’s disease (AD), and is the first of three similar antibodies that ProMIS is working to move into clinical testing in patients.
PMN310 works by binding to neurotoxic forms of amyloid beta, a sticky protein that is found on the fatty membrane of nerve cells. Pieces of this protein can break from the membrane and clump together, forming the abnormal and misfolded — or prion-like — plaque clumps that are believed to be one of the principal cause of brain cell death and tissue loss in Alzheimer’s patients.
How PMN310 works
Current evidence suggests that amyloid beta oligomers (a compound made of monomers) are more toxic to neurons than single amyloid beta pieces (monomers), fibrils, or plaques.
PMN310 has the ability to selectively target and neutralize toxic amyloid beta clumps by binding specifically to these prion-like oligomers — and not the abundant but less toxic monomers, fibrils, or plaques — to potentially improve the treatment’s effectiveness in preventing neurodegeneration. Greater efficacy can also mean a lower dose is needed, so treatment may be safer and better tolerated.
ProMIS Neurosciences’ proprietary discovery platform, called Collective Coordinate, helped researchers identify five different targets on toxic amyloid beta strains, showing that the strain-specific epitopes are shaped differently than the fibrils that make up most brain plaques.
Researchers believe that monoclonal antibodies, such as PMN310, by selectively binding to toxic amyloid beta oligomers will stop them from propagating in the brain.
PMN310’s neuroprotective effect was investigated in mice. Researchers injected prion-like forms of amyloid beta into the brains of mice, causing a neurological deficit that was then assessed in a memory-behavior test called object recognition. Normal mice exposed to an object remember it when it is seen for a second time and don’t pause to study it again. Mice with induced amyloid beta damage, however, lost the ability to discriminate between familiar and new objects, and spent similar amounts of time exploring both objects.
After being treated with PMN310, these mice returned to normal behavior, distinguishing between new and known objects in their explorations.
Researchers concluded, based on these observations, that PMN310 may work to prevent the short-term memory loss caused by toxic amyloid beta.
PMN301 is in late preclinical development, and ProMIS plans to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration in late 2018. The company’s goal is to start a clinical trial of PMN301 by 2019, making it the first monoclonal antibody to be tested in patients.
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