SAGE-718 Fails Phase 2 Study, Foralumab Dampens Microglial Activation, MDA and FARA Collaborate on Gene Therapy Studies

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

Sage Therapeutics recently announced topline data from its pivotal phase 2 PRECEDENT study, with results showing that SAGE-718, an investigational agent, did not demonstrate statistically significant differences vs placebo on the primary end point in patients with Parkinson disease (PD) who had mild cognitive impairment (MCI). The company still plans to report topline data from studies assessing the NMDA receptor positive allosteric modulator in patients with Alzheimer disease (AD) and Huntington disease (HD) later this year. After 6 weeks of treatment, those on SAGE-718 failed to distinguish themselves from placebo on the primary end point of Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Test score. The trial, which randomly assigned 86 patients to either study drug or placebo, showed no between-group differences on other exploratory end points such as SCOPA-Cog.

Significant findings from an open-label expanded-access program revealed that treatment with investigational foralumab (Tiziana Life Sciences) resulted in damped microglial activation and clinical stability in patients with non-active secondary progressive multiple sclerosis (na-SPMS) who had progression independent of relapses (PIRA). Investigators are planning a double-blind, placebo-controlled, dose-ranging study of the agent in this population using (F-18)PBR06-PET, the main tool used to measure microglial activation, as a primary end point. At both the 3 and 6 month time points, 5 of 6 foralumab-treated patients (83%; 95% CI, 44%-97%) demonstrated a qualitative reduction in (F-18)PBR06-PET in multiple brain regions.

According to an announcement from the Muscular Dystrophy Association (MDA) and the Friedreich’s Ataxia Research Alliance (FARA), the 2 organizations have committed a $300,000 research grant to study novel genetic technologies to treat Friedreich ataxia (FA), a rare neuromuscular disorder. The grant, awarded to several notable research physicians, involves prime editing (PE), a next-generation CRISPR gene editing tool that aims to remove the GAA expansions in the frataxin (FXN), or the underlying root cause of FA. Otherwise known as the Paired Prime Editors to Treat Friedreich’s Ataxia grant, this money will be used to evaluate several PE approaches, including a split prime editing system, in which 2 halves of the PE machinery are delivered as separate molecules. This approach allows researchers the ability to quickly test combinations of editing enzymes with desirable properties. The hope is that the grant will support a diverse number of research opportunities to thereby increase the odds that 1 method will be found successful.

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