Tau Modification Drugs Take a Hit with Negative Trial
Lilly’s Phase 2 trial of its O-GlcNAcase inhibitor ceperognastat failed to meet clinical endpoints. The drug’s adverse events suggest potential off-target effects.
NEWS
Finally, Therapeutic Antibodies Start to Reduce Tangles
Bepranemab results bolster hopes for antibodies targeting tau’s middle section. Whether tangle clearance will improve clinical outcomes remains unclear.
Leqembi: Side Effects No Worse in Clinical Use Than They Were in Trial
ARIA rates have been the same or lower than in the Phase 3 trial. About 9,000 people are being treated in the U.S., half as many in Japan. EMA reverses course, recommending approval.
Donanemab: Small Tweak in Titration, Big Gain in Safety?
By starting at a low dose and upping it stepwise for four months, scientists nearly halved the risk of ARIA while preserving plaque clearance.
Trontinemab Data Strengthen Hope for Brain Shuttles
Trontinemab swooped into the brain and removed amyloid efficiently, while causing few cases of ARIA. One person with cerebrovascular pathology died.
That Mystery “Density” in α-Syn Fibrils: Polyphosphate, Anyone?
Modeling and recombinant protein chemistry suggest that strings of phosphate worm their way through the fibrils. Proof is still needed.
Remembering Bruce Albala, 70, Leader in BACE Inhibitor Development
Albala died suddenly while celebrating his 40th wedding anniversary.
Lysosomal Protein TMEM106b Is Tightly Linked to TDP-43, Tau Pathology
Neurons with TMEM106B aggregates lose nuclear TDP-43 in ALS models. In tauopathy models, they accumulate no p-tau.
SPOTLIGHT
From Madrid, News on Anti-Amyloid and Anti-Tau Immunotherapy
At an airport hotel outside of Madrid, researchers hunkered down for the better part of a week to trade news about clinical trials for Alzheimer’s disease. The field is watching the rollout for lecanemab and donanemab with bated breath, tweaking administration, debating appropriate use, and hoping for no more deaths. As the rollout picks up speed, European regulators reversed their earlier rejection of lecanemab, and this week issued a thumbs up. Meanwhile, brain shuttle versions are on the horizon, led by trontinemab. Tau as a target is beginning to yield to mid-region antibodies, though OGA inhibition in its current form appears too toxic.
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