ATH-1105 Shows Promise as ALS Treatment, Eplontersen Granted Fast Track for ATTR Cardiomyopathy, Poor Oral Health Linked to Brain Profiles

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Welcome to this special edition of Neurology News Network. I’m Marco Meglio.

Athira Pharma recently announced a new publication in Frontiers in Neuroscience that showcased consistent neuroprotective and anti-inflammatory effects of ATH-1105, an investigational agent designed to enhance the neurotrophic hepatocyte growth factor (HGF) system. All told, thesepreclinical data provided a rationale for therapeutic interventions like ATH-1105 that leverage the positive modulation of the HGF pathways as a treatment for ALS. “These data demonstrate that ATH-1105 treatment results in significant, consistent beneficial effects both in cell culture and in vivo models of ALS,: Kevin Church, chief scientific officer at Athira, said in a statement. “Through enhancement of the neurotrophic HGF system, ATH-1105 protects spinal motor neurons from ALS-relevant insults in vitro and in animal models of ALS, prevents the progressive decline of motor and nerve function, reduces inflammation, preserves body weight and extends survival.”

Months after the FDA approved Ionis’ eplontersen (Wainua) as a treatment for polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN), the agency has granted fast track designation for an extended indication to treat adults with ATTR cardiomyopathy (ATTR-CM). The therapy is currently being assessed in the global, phase 3 CARDIO-TTRansform study (NCT04136171), a 1400-patient cohort trial that’s considered the largest of ATTR-CM to date. CARDIO-TTRansform, a multicenter, double-blind study, will randomize patients to receive subcutaneous injections of either eplontersen or placebo once every 4 weeks for up to 140 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A. The primary outcome is the composite outcome of cardiovascular (CV), mortality, and recurrent CV clinical events up to 140 weeks while secondary outcomes include change in 6-minute walk test (6MWT) distance and change in Kansas City Cardiomyopathy Questionnaire scores at week 12

Findings from a cross-sectional study of middle-aged British people without stroke or dementia found that individuals with poor oral health had higher white matter volume (WMH) and worse white matter architecture profiles, even after adjusting for confounding factors. Furthermore, Mendelian randomization (MR) analyses from the study completed in the genetic phase confirmed these findings and provided evidence to support the notion that the observed association between poor oral health and poorer neuroimaging profiles is causal. Data revealed that poor oral health was significantly associated with a 46% increase in WMH volume, a 41% change in aggregate fractional anisotropy and a 42% change in aggregate mean diffusivity (MD) scores.

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