Happy New Year for 2024! [above: Is that a blue space-filling model of amyloid beta behind the neuroscientist?]
Barbie is said to be the #1 highest grossing film of 2023. How was Alzheimer’s Clinical Research in 2023? The alzforum.org has a nice review, calling it a “Bumper Year for Treatment and Science of Alzheimer’s Disease (AD).” No Barbie blockbuster, though.
For ADGadfly, after reporting business news about Leqembi / lecanemab, it meanders a bit. It touches on donanemab (set for approval 2024?), gantenerumab (an endpoints failure reassessed but with positive “hints?”), ARIA and the possible role of complement proteins, along with BACE inhibitors again.
It also mentions other FDA neuro approvals in ALS, lysosomal storage diseases, and a behavior management agent for AD. The basic science review is amazing, but probably still far from therapeutics. In contrast, for 2023 cancer therapeutics, there were over three dozen FDA approvals, albeit most were for new indications.
NEJM January 2024 had a case series of three AD patients who received aducanumab, along with focused ultrasound to try to break down the blood brain barrier (BBB). The BBB is a conceptual barrier (nice review 2023 Nature Open Access) that allows certain things into the brain (anesthetics) more readily than other things (like chemotherapy). Ye Olde Ped Oncologist ADGadfly traversed the BBB with spinal taps for decades, to get the chemo in the right place directly. Interestingly, focused ultrasound by itself may reduce amyloid (their ref 5,6,12,13)
The NEJM report seemed to make a splash, not sure why, with so few patients; there is an editorial (both behind paywalls).
Now for some other papers from which to speculate, catching ADGadfly’s now cataract-free eye:
CSF proteomics 5 subtypes [science loves subtypes, proteomics basically seems like a snapshot of person’s variable protein output, in this case found in the subjects’ cerebrospinal fluid]:
Another new imaging research criteria proposal [a bit controversial, basically amyloid and tau, with less priority on neurodegeneration or vascular issues]:
Smartphone dx [“yeah, there’s an app for that!”]:
Plaque clearance and efficacy? [a news article quoting researchers’ opinions, with a nod to donanemab]:
Proteomics study from UK Biobank [news item, this time protein patterns in plasma (blood fraction) and correlations with AD and other conditions]
Donanemab persists in slowing cognitive decline [the company reported what some might say is good news/bad news at AAIC 2023. Good news is that the donanemab group did seem to decline more slowly than previously reported; the bad news is that the magnitude isn’t great, and even the treated group declines]:
https://www.alzforum.org/news/conference-coverage/donanemab-data-anchors-upbeat-aaic
Bryostatin, which has been around for awhile, yielded some equivocal, some positive results in a 122 subject 6 month trial.
Press releases and AD shorts: Speaking of AAIC, the Alz Assn sponsored meeting with Big Pharma support, their meeting highlights linked here. Agents mentioned to ADGadfly (passed along with no comment): Allopregnanolone (presented at CTAD Oct 2023, page S21).
In the “late-breaking” CTAD presentation for T3D-959, readers gotta love this: there was “an unexpected improvement in ADAS-COG11 [cognitive test] among placebo” subjects, page S37, so it couldn’t meet endpoints. Agent TB006, which purports to work on immune /inflammatory pathways, is in clinical trials.
That female / male issue again, in a meta-analysis, but not to harp on Barbie gender-roles:
Sex (gender) as a baseline factor in AD: [in this systematic review dated 2024, out of 2900+ studies, the authors chose 12 that met their criteria. They found that males and females generally had the same risk of AD progression from MCI. A few additional risk factors were statistically significant: APOE-e4 and depression in women, men who had strokes. Unmarried women seemed to do best (!?). Behind a paywall.]
- “By giving voice to the cognitive dissonance required to be a woman under the patriarchy, you’ve robbed it of its power.” — from the Barbie movie…
Congrats on landing in 2024! I’m glad we made it!