This is like a mystery novel. (Actually, most scientific studies ARE mysteries- because if we knew what we needed to know, there’d be no need to experiment and test. We need to develop a sound hypothesis, based upon what we learned, and then examine how we can extend that knowledge.)

As I said throughout this mini-series (here’s part 1, and this links to part 2), we really don’t know exactly why or how we develop Alzheimer’s- which leaves the 5 million folks over the age of 65 succumbing to the disease with no viable treatment. Some folks fear we can become infected from improperly sterilized surgical equipment, others from blood transfusions (actually, should this be true, it would require manifold doses), and then there’s those genes. Which is why we still have no drugs that can reverse the disease. And, if a subject has the suspect gene variants, diet and exercise really won’t provide much relief or be able to hold the disease in abeyance, either.

The basic knowledge for Alzheimer’s, though, is that it’s multi-factorial. That means poor diet, sedentary lifestyles, exposure to environmental chemical irritants, chronic inflammation, and genetics all play a part to one succumbing to Alzheimer’s. And, folks who develop Alzheimer’s manifest other brain pathologies, further complicating their study and the ability to discern results.

Moreover, the brain can’t be easily accessed by clinicians. We can’t take repeated biopsies to see how or where a drug may be providing some positive result.

Given these facts (and what we’ve discussed over the past few days), it’s not surprising that Pfizer pulled out of its Alzheimer’s drug development program. So did Merck. And, Axovant Sciences found its darling failing to routinely work against Alzheimer’s or other dementia.

There have been about 400 failed clinical trials for Alzheimer’s therapies- and 14 years since a new drug made its way through the channels to treat patients. Only one- aducanumab (developed at the University of Zurich and now controlled by the biotech firm, Biogen)- has demonstrated significant success in eradicating amyloids. Still, this drug is not ready for prime time.

But, aducanumab is a different sort of therapy. It’s a human monoclonal antibody, one which targets beta amyloid (the protein that accumulates in the brain). It actually binds to the amyloid plaques in the brain, enabling microglial cells to remove the offending structures. Normally, beta amyloid (Aβ) appears as a single protein (monomer) in the brain. But, with the development of Alzheimer’s, the protein clumps and aggregates (forming oligomers) and these preclude rapid communication among the brain cells- and this syndrome also leads to brain cell death.

With monthly infusions of the monoclonal antibody (as found during the phase 1B clinical trials), folks demonstrated a diminished cognitive decline and much lower beta amyloid levels. The testing has involved multiple doses (low, medium, high- plus a control)- and those receiving the highest dose (and the longer duration treatments) manifested the best results. (After a year at the highest doses, the PET scan was devoid of red- which means the beta amyloid was eradicated from the subjects’ brains.) But, on the other hand,  those folks with the APOE4 gene exhibited some brain swelling and bleeding.

Let’s hope the results from the phase 3 clinical trials (actually, fairly large tests- 300 centers, 20 countries across the world, with a 2700 patient census) continue to prove the value of the drug. But, there are clouds, since Biogen had to increase the sample size (adding 510 more subjects), as the results to date manifested a little too much “noise”. (That meant the test data could not be used to clearly prove drug efficacy; the data wasn’t clear-cut enough).

Sheesh!

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