About the Study: In this randomized clinical trial, despite the relevance of the eIF2b activation pathway in ALS disease biology and supporting evidence of proof of mechanism and optimal dose selection in a prior phase 1B ALS clinical trial, 200-mg/d DNL343 did not show evidence of slowing disease progression in ALS, highlighting the need for alternative therapeutic approaches.
Corresponding Author : Sabrina Paganoni, MD, PhD, Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, 165 Cambridge St, Ste 600, Boston, MA 02114 ( spaganoni@mgh.harvard.edu ).
10.1001/jamanetworkopen.2026.34809
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