A type of immunotherapy, PMN330 is a monoclonal antibody that targets a form of amyloid beta (Aβ), one of the proteins whose accumulation damages and kills brain cells, leading to the progressive memory loss that characterizes this disease.
How PMN330 works
Aβ is a protein that has long been associated with Alzheimer’s disease, but research now suggests that only certain forms of Aβ are toxic to brain cells as evidenced by the fact that people with the larger, more visible collections of protein do not always have Alzheimer’s disease. Moreover, patients with severe Alzheimer’s disease do not necessarily have greater plaque buildup in the brain than those with less severe disease.
The toxic forms of Aβ are thought to be relatively small protein clumps, called oligomers, that behave in a similar way to prions. Prions are small proteins that cause other proteins to misfold and multiply in the brain, destroying brain cells in the process.
PMN330 targets prion-like Aβ to block the spread of the toxic protein and keep it from damaging nerve cells in the brain.
PMN330 is the third Alzheimer’s disease treatment being developed by ProMIS that has met the criteria to be a validated lead product. A lead product is a therapy with the potential to succeed in clinical studies, and a validated product is one that has shown sufficient evidence of its ability to bind to intended targets and act in the body.
Initial laboratory tests demonstrated that PMN330 binds specifically to the toxic form of Aβ and that this binding keeps the toxic proteins from multiplying and damaging nerve cells.
Next, investigators used a memory-behavior test to see whether PMN330 prevented short-term memory loss in mice injected with toxic Aβ. Healthy mice introduced to a new object are known to remember it when it is seen again, spending less time exploring the object than they did when they were first presented with it.
Aβ-injected mice in the ProMIS memory test showed signs of not remembering an object they had already explored, and spent about the same amount of time studying it again as they did a newly introduced object.
When these mice were treated with PMN330, their short-term memory loss seemed to have been prevented. The finding was supported by changes in measures of biomarkers associated with inflammation and neuroprotection.
The company’s two other lead potential Alzheimer’s disease treatments, PMN310 and PMN350, are also monoclonal antibodies directed against prion-like forms of amyloid beta. All three products have differing targets on these toxic proteins, meaning they bind to different regions.
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