Objective: To characterize the genetic and biomarker profile of patients with Progressive Supranuclear Palsy (PSP) and the relationship of potential biomarkers with baseline disease severity.

Background: ARISE (NCT02985879) is an ongoing phase 2, randomized, double-blind, placebo-controlled trial of the anti-tau antibody, ABBV-8E12, in patients with possible or probable PSP. Genetic, biochemical, and volumetric MRI (vMRI) data were obtained as potential biomarkers of disease severity. A preliminary analysis was conducted on the first 30 patients enrolled.

Method: Baseline disease severity was assessed by the PSP Rating Scale (PSPRS). MAPT haplotyping was determined for all enrolled subjects. At screening, neurofilament light chain (NfL) and total tau levels were measured in plasma and/or CSF. Quantitative vMRI measurements were obtained in the third ventricle, frontal lobe, and midbrain. Individual MRI measurements were adjusted for intracranial volume.  Association between variables was evaluated using Pearson’s correlation coefficient.

Results: A total of 378 patients with PSP were randomized into ARISE, and ongoing haplotyping analysis identified several H1-clade polymorphisms in MAPT. Baseline characteristics for the first 30 patients are described. [table 1] CSF and plasma tau concentrations were not significantly correlated with each other or with PSPRS. There was a positive trend between plasma NfL levels and PSPRS (r=0.33, p=0.089). Higher plasma NfL was significantly correlated with lower whole brain (r= –0.59, p=0.002), midbrain (r=–0.44, p=0.024), and frontal lobe volume (r= –0.55, p=0.004). PSPRS total score also significantly correlated with lower whole brain (r=–0.48, p=0.010), midbrain (r=–0.43, p=0.023), and frontal lobe volume (r=–0.40, p=0.033). Midbrain volume was significantly associated with the ocular motor, gait, and bulbar domains.

Conclusion: Baseline characteristics of patients in the ARISE trial are comparable to PSP patient profiles described in the literature, including an apparent predominant H1 MAPT haplotype genetic profile. Data indicated a positive trend between plasma NfL and disease severity. Lower whole brain, midbrain, and frontal lobe volumes were significantly correlated with both plasma NfL levels and total PSPRS disease severity.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-correlates-of-genetic-and-biomarker-profiles-in-patients-with-progressive-supranuclear-palsy-data-from-the-arise-study/