𝐈𝐬 𝐓𝐃𝐏-𝟒𝟑 𝐭𝐡𝐞 𝐥𝐲𝐧𝐜𝐡𝐩𝐢𝐧 𝐟𝐨𝐫 𝐟𝐢𝐧𝐝𝐢𝐧𝐠 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 𝐟𝐨𝐫 𝐀𝐋𝐒? Two pathologies, one protein The field has increasingly recognized that TDP-43 dysfunction operates through two parallel mechanisms. The cytoplasmic gain-of-function toxicity that CTx1000 directly targets is only half the story. Equally consequential is the loss of normal nuclear TDP-43 function, particularly its role in RNA splicing […]

𝐓𝐚𝐫𝐠𝐞𝐭𝐢𝐧𝐠 𝐓𝐃𝐏-𝟒𝟑 𝐢𝐧 𝐀𝐋𝐒: 𝐑𝐞𝐠𝐮𝐥𝐚𝐭𝐨𝐫𝐲 𝐡𝐮𝐫𝐝𝐥𝐞𝐬, 𝐭𝐫𝐢𝐚𝐥 𝐝𝐞𝐬𝐢𝐠𝐧 𝐝𝐞𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐢𝐞𝐬, 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐜𝐚𝐮𝐬𝐚𝐥 𝐞𝐯𝐢𝐝𝐞𝐧𝐜𝐞 𝐠𝐚𝐩 𝐟𝐨𝐫 𝐂𝐓𝐱𝟏𝟎𝟎𝟎, Michael A.S. Guth, Drug Discovery Today, Volume 31, Issue 5, 2026, 104752, ISSN 1359-6446, https://doi.org/10.1016/j.drudis.2026.104752. https://www.sciencedirect.com/science/article/pii/S1359644626001571 Highlights • Over 60 amyotrophic lateral sclerosis (ALS) drug failures since 1995 underscore a persistent trial graveyard. • CTX1000’s degron fusion selectively clears […]

The Dual Sequestration Hypothesis as a Clinicopathological Synthesis We propose the DSH as a unifying framework to resolve these converging crises. This clinicopathological update posits that sporadic Alzheimer’s disease, particularly in its modern manifestation, could be understood as a disease of maladaptive innate immunity. The DSH suggests reframing Aβ and tau pathologies not as intrinsic pathogens […]

𝐓𝐡𝐞 𝐌𝐢𝐜𝐫𝐨𝐩𝐥𝐚𝐬𝐭𝐢𝐜 𝐓𝐡𝐫𝐞𝐚𝐭 𝐀𝐜𝐜𝐞𝐥𝐞𝐫𝐚𝐭𝐢𝐧𝐠 𝐀𝐥𝐳𝐡𝐞𝐢𝐦𝐞𝐫’𝐬 𝐃𝐢𝐬𝐞𝐚𝐬𝐞 Parallel to this clinical quandary, environmental science has uncovered a novel, pervasive threat to neural integrity. Micro- and nanoplastics, ubiquitous contaminants of the Anthropocene, have infiltrated global ecosystems and, consequently, the human body. These synthetic polymer particles have been confirmed to breach critical biological barriers and have been detected […]