One CAR T infusion put 3 of 6 resistant arthritis patients into remission
Disease activity fell in all 6 adults with treatment-resistant rheumatoid arthritis after one CAR T infusion, and 3 entered remission. Alzheimer research separately tracks an APOE-independent multiancestry risk score and the escape of tau seeds from stiffened intracellular vesicles. The first result comes from a small safety study without a comparison arm; the Alzheimer findings combine observational human data with worm and cell models.
Science··Morning
Arthritis receded during drug-free follow-up
In the nonrandomized phase 1 part of COMPARE, 6 adults with rheumatoid arthritis resistant to standard treatment stopped disease-modifying drugs and received one infusion of CD19-targeted CAR T cells made from their own cells. Disease activity fell in everyone during 36–52 weeks of follow-up; 3 of 6 patients reached DAS28-CRP remission and an ACR70 response. The study was primarily designed to test safety in the first 4 weeks. Cytokine release syndrome occurred in everyone but remained at grade 1 or 2, and no neurotoxicity occurred. The lack of a comparison arm and a large patient group keeps the efficacy result preliminary.[1]
A risk score built for diverse ancestries
A Nature Genetics team responded to the inconsistent performance of earlier Alzheimer polygenic risk scores across ancestries by developing a multiancestry score independent of the APOE region. It was built from association data in European ancestry, African American, Caribbean Hispanic and East Asian cohorts, tested in independent groups and associated with disease in several populations. Higher scores also accompanied poorer memory, executive function and language performance, greater neuropathological burden, smaller hippocampal volume and shifts in tau and amyloid biomarkers. The authors present it as one component of broader risk assessment, rather than a test that can diagnose Alzheimer disease by itself.[2]
A cellular escape route for tau seeds
The eLife study examined how tau aggregates can spread inside cells in Caenorhabditis elegans and human cell-culture models. Silencing sphingolipid-metabolism genes lowered the membrane fluidity of endolysosomal vesicles and made them rupture more often. Accumulating tau aggregates worsened the stiffening and damage and promoted seeded tau aggregation. Unsaturated fatty acids improved membrane fluidity in cell models, suppressed vesicle rupture and seeded tau aggregation, and eased tau-associated neurotoxicity in Caenorhabditis elegans. The findings remain at the worm and cell-culture level; no treatment effect was measured in people.[3]
