The biomarker neurofilament light (NfL) has taken on a central role in neurology drug development, with drugs being approved or dropped based on what they do to NfL. We, like everyone, long assumed increases in NfL always meant neuronal damage, and decreases in NfL meant amelioration thereof. Today we report some data that have made us think there may be exceptions. In human, mouse, and cell culture we see NfL rise after minocycline treatment. The increase is very specific to NfL, has rapid washout kinetics distinct from neuronal injury, and does not seem to be associated with any neurotoxic signature. Our hypothesis: minocycline, by inhibiting microglial activity, may block clearance of NfL. Pre-print: https://lnkd.in/eQs_dzHM Blog post: https://lnkd.in/eTeqQ6yK Open data & source code: https://lnkd.in/ejT5cMed
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With more and more endpoints of trials measuring nfl and go/no go decisions depending on its level, we must aware the likely drawbacks of such nfl subservience
The biomarker neurofilament light (NfL) has taken on a central role in neurology drug development, with drugs being approved or dropped based on what they do to NfL. We, like everyone, long assumed increases in NfL always meant neuronal damage, and decreases in NfL meant amelioration thereof. Today we report some data that have made us think there may be exceptions. In human, mouse, and cell culture we see NfL rise after minocycline treatment. The increase is very specific to NfL, has rapid washout kinetics distinct from neuronal injury, and does not seem to be associated with any neurotoxic signature. Our hypothesis: minocycline, by inhibiting microglial activity, may block clearance of NfL. Pre-print: https://lnkd.in/eQs_dzHM Blog post: https://lnkd.in/eTeqQ6yK Open data & source code: https://lnkd.in/ejT5cMed
Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker
medrxiv.org
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Hydration Methods for Cisplatin Containing Chemotherapy: A Systematic Review https://buff.ly/3OZCUJn This study from The Oncologist journal aims to provide objective evidence on the optimal design of hydration schemes to prevent cisplatin-induced nephrotoxicity based on an update of the literature.
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A recent study introduces two novel AAV capsids, Pep2hSC1 and Pep2hSC2, developed through functional transduction-RNA selection, demonstrating potent transgene delivery capabilities across various models. These breakthroughs hold potential for addressing disorders related to Schwann cells and peripheral nervous system injuries. #GeneTherapy #BiomedicalResearch #GeneticDisorders #AAVVectors #SchwannCells #ClinicalTrials #TransgeneDelivery #TherapeuticSolutions #IncurableDiseases #MedicalInnovation https://lnkd.in/eGZEXZUX
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Public Health Consultant | Health Advisor |Training Expert | Health and Climate Change Top 100 Moroccan scientists (Medical Sciences)🇲🇦 Top 04 Moroccan Scientists (Dentistry) 🇲🇦Source:ADScientificindex.com (2024)🇺🇸
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Dreamster dedicated to the prevention and treatment of mental health disorders that affect at least 1 in 6 people worldwide!
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Amyotropric Lateral Sclerosis (ALS) - A Giving Smarter Guide by Sylvie Raver, PhD, Quinton Banks, Megan van der Horst, Cara Altimus for Milken Institute https://lnkd.in/dgV5hDch. Further resources of interest: 1) Trends in drug development for amyotrophic lateral sclerosis https://lnkd.in/d7NHuxFD 2) Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation (2023) https://lnkd.in/din_JqJZ 3) Guiding principles for drug discovery and development in amyotrophic lateral sclerosis (ALS) https://lnkd.in/dkFG-EPj
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Discover the latest research on how METTL1-driven tRNA m7G modification plays a crucial role in AML leukemogenesis through tRNA-modulated translational control. Read the insightful article published by Physicians Weekly in January 2024, summarizing the findings of Zhao et al.
Analyzing METTL1-Driven tRNA m7G Modification Facilitates AML Leukemogenesis Through tRNA-Modulated Translational Control
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Professor of Neurology at University College London
3moOh this is YOU! This preprint has been making ripples in my tiny world but I scrolled right past the author list. It’s great and important work. The lesson for me is that an NFL increase on treatment may be tolerable if (1) you know why it’s happening and (2) you have reason to believe that it will be worth the wait, in the full context, for it to come down. I do worry that lots of people whose drugs have produced big NFL rises for the more prosaic reason will cite your work as a reason to press on regardless – investors are likely to be especially susceptible to this tactic - but that is not your problem!