The ALZFORUM 2018 Retrospective

ALZFORUM should be on your reading list. It is a shining example of what can be accomplished online in focused patient advocacy, given sufficient funding and a good team. The Alzheimer's research community and its surrounding institutions represent a sizable fraction of all funding for the investigation and treatment of age-related disease these days, at least for public funding where such data is more reliably tracked. There is thus more money to go around for supporting initiatives like ALZFORUM than is the case in other fields, but it - of course - still requires a quality team to produce quality work. In this lengthy post, developments in Alzheimer's research over the course of 2018 are reviewed in detail. It is an exciting time for the field, given the first signs of progress after long years of failure in attempts to clear amyloid-β from the brain, and also given the rise of radical new directions in the development of therapies.

In 2018, a mix of positive and negative trial data left the field with a sense of unease that, in order to meet its goal of a game-changing treatment by 2025, everything has to go right from now on. On the up side, the SPRINT MIND trial indicated that keeping systolic blood pressure under 120 mm Hg in a person's 60s reduced mild cognitive impairment four years later by 19 percent, while in a Phase 2B trial, the anti-Aβ protofibril immunotherapy BAN2401 seemed to both mop up Aβ plaques from the brain and slow cognitive decline in people with early Alzheimer's disease (AD). Both trials generated optimism about early intervention.

BAN2401 joins the aducanumab, gantenerumab, and N3pG antibodies in removing amyloid plaques in the brain. Up to half the participants fell below the threshold for amyloid positivity over the course of one to two years. Convinced that their early antibody efforts were too timid, researchers at boosted dosing of gantenerumab, crenezumab, and N3pG, respectively, but as yet, none of these treatments has been shown to slow or halt dementia.

Taking a different tack, researchers claimed they cleared Aβ from the brain in a procedure akin to an engine oil change. They removed Aβ from blood by way of plasmapheresis, in which a person's plasma is exchanged for a solution of 5 percent albumin, the principal carrier of Aβ in the blood, and in some cases also containing blood immunoglobulins that bind Aβ. These carrier proteins indirectly coax Aβ from the brain, the theory goes. The Phase 2b/3 AMBAR (Alzheimer's Management by Albumin Replacement) trial missed its endpoint, but subgroup analysis suggested cognitive decline slowed in participants with moderate, though not mild, AD. Whether the albumin or the immunoglobulins did the trick is unclear, and the company plans to run a new trial to clarify. A related approach of soothing the "inflammaging" brain, either with whole plasma or defined fractions from the blood of young adults, is in early stage trials.



When this article appeared some days ago, I reviewed this year's FA! articles. My conclusion was that the main practical advances this year have been in the tissue engineering field (many small and useful steps) and also the good results of Gensight's mitosens trial.

Of course, there have been a lot of scientific results (increasing our theoretical knowledge) and very good funding news (mostly in cryptocurrencies), but as for the practical, engineering results, those were the main advances, I think.

Posted by: Antonio at December 31st, 2018 6:55 AM
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