CMA · Senescence · Preclinical
Decline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cells
Nature Aging (published October 5, 2026) links age-related CMA failure in fibroblasts and macrophages to a more toxic
SASP and weaker macrophage phagocytosis and efferocytosis. Oral CMA activator CA77.1 cut senescent-cell burden in aged
mice and eased bleomycin lung fibrosis when started early. Human IPF lung lysosomes showed reduced CMA activity.
Caveat: Mouse and correlative human tissue work. CA77.1 is not an approved therapy. The IPF human data are not a clinical trial. Einstein discloses related intellectual property.
Nature Aging →
EurekAlert →
AATD · RNA editing · Regulatory pathway
FDA feedback supports registrational pathway for WVE-006 RNA editing in AATD
Wave Life Sciences (October 1 press release; clinical coverage October 5) reports FDA alignment on one two-year
registrational trial for GalNAc-conjugated ADAR RNA editor WVE-006 in alpha-1 antitrypsin deficiency, with a one-year
biomarker interim that could support accelerated approval. FDA also accepted Wave’s LC-MS M-AAT/Z-AAT assay.
RestorAATion-2 600 mg monthly cohort data are expected in the fourth quarter of 2026. The approach contrasts with
permanent genome editors (for example BEAM-302) also in AATD.
Caveat: Regulatory pathway and Phase 1b/2a program — not approval. Repeat dosing is required. Efficacy and safety for registrational endpoints are not yet established.
Wave Life Sciences IR →
CRISPR Medicine News →
Senolytics · Fibrotic MASH · Phase 2 RCT
Senolytics dasatinib and quercetin in fibrotic MASH: proof-of-principle randomized trial
Nature Metabolism (published October 1, 2026) reports a single-center phase-2 double-blind randomized trial (n=31;
NCT05506488): intermittent dasatinib 100 mg plus quercetin 1,000 mg (3 days per week for 3 weeks, three 7-week cycles)
versus placebo. The primary endpoint (≥1 fibrosis stage improvement without MASH worsening on paired biopsies) was
47% versus 7% (P=0.02); MASH resolution was 53% versus 7% (P=0.02). Single-nucleus RNA sequencing showed lower
senescence and fibrotic signatures. Adverse events were more frequent with D+Q (82% versus 43%) but self-limiting.
Caveat: Small single-center proof-of-principle; not practice-changing. Dasatinib carries known toxicities and needs larger multicenter confirmation. Not treatment guidance.
Nature Metabolism →
