A type of immunotherapy, PMBN330 is a monoclonal antibody that targets a form of amyloid beta, one of the proteins whose accumulation damages and kills brain cells, leading to the progressive memory loss that characterizes this disease.
How PMN330 works
Amyloid beta (AB) is a protein that has long been associated with AD, but research now suggests that only certain forms of amyloid beta are toxic to brain cells. People with AB plaques — the larger, more visible collections of protein — do not always have Alzheimer’s, while patients with severe Alzheimer’s do not necessarily have greater plaque buildup in the brain than those with less severe disease.
The toxic forms of AB 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 amyloid beta to block the spread of the toxic protein and keep it from damaging nerve cells in the brain.
Studies of PMN330
PMN330 is the third Alzheimer’s drug 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 in tests sufficient evidence of its ability to bind to intended targets (binding affinity) and act in the body.
In initial laboratory tests, PMN330 demonstrated that it binds specifically to the toxic form of AB, 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 AB. Healthy mice introduced to a new object are known to remember it when it’s seen again, spending less time exploring the object than they did when first presented with it.
AB-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, however, new test results suggested the drug prevented short-term memory loss in these mice. The finding was supported by changes in measures of biomarkers associated with inflammation and neuroprotection.
The company’s two other lead potential Alzheimer’s treatments, PMN310 and PMN350, are also monoclonal antibodies directed against prion-like forms of amyloid beta. But all three lead products have differing targets on these toxic proteins, meaning they bind to different regions.
PMN310 is on track to be the first to be tested in patients, with ProMIS planning to enter it in a clinical trial by 2019.
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