While large pharmaceutical companies have been reporting failure after expensive failure in their efforts to develop an Alzheimer’s drug by targeting amyloid, a growing number of startups have been quietly trying different strategies. One approach, pioneered by South San Francisco-based Cortexyme, is based on an old idea that is gaining traction after being shunted aside for decades: that an infectious agent causes Alzheimer’s, and that targeting that pathogen and the neuronal havoc it wreaks can stop and even reverse some aspects of the disease.
Proponents of the amyloid hypothesis — that clumps of this protein fragment cause the disease and that eliminating them can stop or reverse it — “have led this field astray for 30 years” said Cortexyme co-founder and CEO Casey Lynch in an email. “Unfortunately, the influence of the few and the groupthink is continuing.”
The amyloid dogma not only “unnecessarily consumes funding,” she added. It may also harm patients who volunteer for clinical trials: Several experimental drugs that block the production of beta-amyloid in people with no symptoms of Alzheimer’s, she pointed out, have caused cognitive worsening, according to studies in 2012, 2013, 2018, and last month. “We cannot continue to let the amyloid ‘cabal’ define the conversation.”
Elsewhere, studies have invoked other organisms eg herpes and fungi …
If this is so, and the infective hypothesis holds, then Alzheimer’s Disease may be at a common end pathway of several different infections, with inflammation being a common feature leading to neurodegeneration and death ..
Thus only inhibition of P gingivalis toxins may not address the whole AD population in the clinical studies ..
Immunomodulation, antiinflammation and neuroregeneration may thus offer more broadcast therapeutic intervention
This well-written report from Sharon Begley is timely now that Cortexyme has come out of stealth mode. Let’s hope their trial results are promising, but kudos to the company for trying something other than the traditional anti-amyloid approach. The role of other microbes found in brains must also be elucidated. Fortunately, the NIA has recently elevated “pathogens in Alzheimer’s” to “high priority” for research grants, and likely has millions of dollars to award to worthy proposals.
Do you know if people who are edentulous were involved in the study?
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