PMN350 is an experimental treatment being developed by ProMIS Neurosciences. It is a monoclonal antibody designed to treat Alzheimer’s disease by targeting toxic forms of beta-amyloid proteins, a hallmark of the disease.
PMN350 is the company’s second lead product for Alzheimer’s disease. A lead product is a compound that has passed a number of tests showing that it is effective and will likely be a successful treatment for a disease.
How PMN350 works
Preclinical studies have supported an association between the buildup of beta-amyloid protein plaques in the brain and the development of Alzheimer’s disease. 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 the disease. Oligomers’ toxicity stems from the fact that they have the ability to make surrounding proteins mis-fold in a way similar to prions. Prions are small particles composed of an abnormally folded protein that cause other proteins to also mis-fold, leading to progressive neurodegenerative conditions.
PMN350 binds to toxic oligomers and it is hoped that it will block their spread and protect nerve cells from injury.
PMN350 research
ProMIS tested PMN350 in the laboratory to verify that it could bind to the toxic forms of beta-amyloid. Researchers also verified that the compound could block the spread of the toxic proteins throughout the brain and stop them from killing 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 beta-amyloid that were then treated with PMN350.
Normally, mice exposed to an object remember the object and when re-exposed to it, spend less time exploring it. But mice injected with toxic forms of beta-amyloid lose their ability to remember and discriminate between familiar and new objects; they spend equivalent amounts of time exploring both new objects and those to which they had already been exposed.
When researchers gave PMN350 to mice injected with beta-amyloid, the memory-behavior test showed that signs of their memory loss disappeared, suggesting that the treatment preserved the animals’ cognitive function. The compound’s benefit was supported by improvements in the levels of biomarkers associated with neuroprotection and molecular inflammation.
Other information
In addition to PMN350, ProMIS is developing two other validated lead monoclonal antibodies for the treatment of Alzheimer’s disease, PMN310 and PMN330. These are designed to target different regions on the toxic beta-amyloid protein.
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