Over the last decade, many of the attempted treatments for Alzheimer’s Disease have focused on the build of plaques in the brain associated with malformed proteins. It certainly seems like a reasonable approach, as these “amyloid beta plaques” are not only directly connected to damage to areas of the brain, they’re similar to the protein accumulations that have been noted in other brain-diseases of both humans and animals. So a whole series of drug trials have come and gone using various approaches meant to either prevent or remove these plaques. Unfortunately, no matter how reasonable this approach would seem, and no matter how obvious the connection presents, treatments following this course have generated very little sign of offering a significant, broadly-applicable solution to either preventing or treating Alzheimer’s and similar conditions.
But a study published this week in Science looks at a different aspect of Alzheimer’s, along with other brain diseases. It offers some intriguing hints about not just the disease mechanism, but also suggests that, in animal models at least, some of the resulting damage can be rolled back.
The study looks specifically at the “blood brain barrier.” The boundary between the vascular system that carries blood around the body, and the brain has been long recognized. Yes, cells of the brain need nutrition—quite a lot of it, in fact—but the mechanisms by which that happens block many compounds from entering the brain. It’s a system that both protects the brain from a number of disease mechanisms, and makes it more difficult for many drugs to be introduced because they simply can’t jump that boundary.
However, previous studies have found that in aging brains, and particularly those of patients with epilepsy or Alzheimer’s, the blood brain barrier becomes less effective. More, and more varied, compounds cross from the blood into the brain. Which is part of how those troublesome plaques get formed.
The new study, headed by scientists at the University of California, Berkeley, looks at that barrier breakdown on the molecular level. It ties the increasing failure of the barrier to an increase in a single enzyme called “transforming growth factor–β (TGFβ).” It also shows that, in mice at least, reducing the action of TGFβ reversed the effects of neural decline.
Hopeful studies on Alzheimer’s aren’t rare. As someone who suffers from the best early predictor of the disease (high blood pressure that developed in youth and persisted through middle age), I can testify that it is never difficult to find some new, apparently promising study when the latest round of being unable to locate my phone makes me start wondering how many little pink plaques are currently decorating my neural folds.
But, even sorting out the pseudoscience junk studies, many of the papers making it to publication seem to reflect treatments that are either following routes only very slightly removed from past failures, or looking at factors so broad they seem difficult or impossible to translate into a treatment anywhere in the near future.
The TGFβ approach appears, at first glance, to offer both something genuinely different, and genuinely encouraging. However … it’s early. Very, very early. Early like we’re talking about mice and every damn thing seems to work on mice early. Even so, it’s good to see something different enough to be interesting. This study suggests that the breakdown of the blood brain barrier is not the final stage of a decaying system, but one of the “earliest triggers of neurological aging.” If that’s the case, then restoring that barrier could be therapeutic well beyond just treating Alzheimer’s (if it’s possible to ever use “just” in association with something so terrible).
There’s also another interesting aspect of this study in that the ability to move compounds across the blood brain barrier is exactly why a currently available drug seemed to show promise in treating Alzheimer’s even though researchers were dismissive of early reports.
Back in June, reports emerged that a drug already on the marker from Pfizer—the commonly used arthritis drug, Enbrel—resulted in an astounding 64% lower incidence of developing Alzheimer’s. Not only is this a drug already on the market, it’s very close to losing its patent and becoming generic. So close, in fact, that Pfizer appears to have failed to follow up these rather amazing statistics … and they’ve had those statistics since 2015.
Another big reason this result was ignored: It was thought that Enbrel could not cross the blood brain barrier. But tie that information to the new study and … maybe the reason that Enbrel is being effective is because one of the first things that happens with developing neurological disorders is that the barrier starts to weaken. This suggests not only an exciting range of possible treatments ruled out in the past because they would be blocked by a healthy barrier, but leads to the idea that drugs might be tailored so that they would only treat those who needed them because their barriers had started to drop.
In any case, both these developments seem to offer some genuine hope — and a new light — on a subject where both are badly needed.