Beta-amyloids, also called amyloid-beta or AB proteins, clump together to form plaques that collect in the brain, disrupting nerve cell communication. As the proteins accumulate, brain cells begin to die, eventually leading to the memory loss associated with Alzheimer’s.
ProMIS Neurosciences is developing and testing the drug.
How PMN350 works
Preclinical-trial studies have supported an association between the build-up of amyloid-beta protein plaque and the development of Alzheimer’s.
However, scientists now recognize that smaller toxic protein clumps, known as oligomers, and not the plaques are the primary driver of the loss of nerve cells associated with the development and progression of Alzheimer’s. Oligomers’ toxicity stems from the fact that they have the ability to make surrounding proteins misfold in a way similar to prions. Prions are small particles composed of an abnormally folded protein that cause progressive neurodegenerative conditions.
PMN350 binds to toxic AB oligomers, blocking their spread and protecting nerve cells from injury.
Pre-clinical studies of PMN350
To select PMN350 as its second lead product for Alzheimer’s, ProMIS performed a number of rigorous screening and validation tests. A lead product is a potential drug that has passed a number of tests showing that it is effective and will likely be a successful treatment for a disease.
ProMIS tested PMN350 in the laboratory to verify that it could bind to the toxic forms of AB that drive the development of Alzheimer’s. In addition, researchers verified that the drug could block the spread of the toxic proteins throughout the brain and stop the killing of nerve cells.
Researchers then evaluated PMN350’s ability to protect nerve cells by preventing short-term memory loss. They did this by using a memory behavior test in mice injected with toxic forms of AB, that were then treated with PMN350.
Normally, mice exposed to an object remember the object when re-exposed to it and spend less time exploring it the second time around. But mice injected with toxic forms of AB lose their ability to remember and discriminate between familiar and new objects. They spend equivalent amounts of time exploring both new objects and those they were exposed to before, suggesting they have lost their short-term memory.
When researchers gave PMN350 to mice injected with AB, the memory behavior test showed that signs of their memory loss disappeared, suggesting that the drug preserved the animals’ cognitive function. The drug’s benefit was supported by improvements in the levels of biomarkers in the mice that are associated with neuroprotection and molecular inflammation.
In addition to PMN350, ProMIS has developed two additional validated lead monoclonal antibodies for treating Alzheimer’s, PMN310 and PMN330. These are designed to target different regions on the toxic AB protein.
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