The following is a summary of “Association of Plasma Phosphorylated Tau With the Response to Neflamapimod Treatment in Patients With Dementia With Lewy Bodies,” published in the September 2023 issue of Neurology by Alam et al.

Co-pathology with Alzheimer’s disease (AD) is associated with accelerated cognitive decline and more extensive cortical atrophy in a proportion of patients with dementia with Lewy bodies (DLB).

Researchers performed a retrospective study to evaluate the relationship between plasma tau phosphorylated at residue 181 (ptau181) and the treatment effects of neflamapimod (a p38α kinase inhibitor) in DLB.

They randomized (1:1), 16-week placebo-controlled clinical trial of neflamapimod in DLB. Pretreatment plasma (i.e., post-hoc), ptau181 levels determined and categorized participants based on a cut-off for AD pathology of 2.2 pg/mL (established in a separate cohort to distinguish AD from healthy controls). Clinical outcomes for comparing placebo with neflamapimod 40mg three times daily (TID; the higher and more clinically active of two studied doses) were analyzed using Mixed Models for Repeated Measures within each sub-group (baseline plasma ptau181 < and ≥2.2 pg/mL).

The results showed pretreatment plasma ptau181 levels were assessed in 85 participants with mild-to-moderate DLB on cholinesterase inhibitors, with 45 below and 40 above the 2.2 pg/mL cut-off at baseline. Participants below the cut-off showed greater improvements in all endpoints assessed at 16 weeks compared to those above the cut-off when taking neflamapimod 40 mg TID. Those below the ptau181 cut-off at baseline exhibited significant enhancements over placebo in an Attention Composite measure (+0.42, 95% CI: 0.07–0.78, P=0.023, d=0.78), the Clinical Dementia Rating Scale Sum of Boxes (−0.60, 95% CI: -1.04, -0.06, P=0.031, d=0.70), the Timed Up and Go test (−3.1 sec, 95%CI: -4.7, -1.6, P<0.001, d=0.74), and International Shopping List Test-Recognition (+1.4, 95% CI: 0.2–2.5, P=0.024, d=1.00).

They concluded that excluding patients with elevated plasma ptau181 enriched DLB patients were more responsive to neflamapimod.

Source: n.neurology.org/content/early/2023/09/01/WNL.0000000000207755#%20