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Introduction/Aims: Lipid peroxidation is thought to play a biologically important role in motor neuron death in amyotrophic lateral sclerosis (ALS). 11,11 Di-deuterated linoleic ethyl ester (RT001) prevents lipid peroxidation in cellular and mitochondrial membranes. Herein we report on the use of RT001 under expanded access (EA).Methods: We provided RT001 to patients with ALS via EA at a single site. The starting dose was 2.88 g/day, which was increased to to 8.64 g/day as tolerated. Participants were not eligible for alternative clinical trials. Participants were followed for adverse events and pharmacokinetic (PK) parameters were measured approximately 3 months after RT001 initiation.Results: Sixteen participants received RT001 (5.6 ± 1.6 g/day; dose range, 1.92 to 8.64 g/day) for a mean period of 10.8 ± 7.1 months. After 3 months of treatment, PK studies showed that RT001 was absorbed, metabolized, and incorporated into red blood cell membranes at concentrations expected to be therapeutic based on in vitro models. The most common adverse events were gastrointestinal, including diarrhea, which occurred in 25% of the participants, and were considered possibly related to RT001. One participant (6%) discontinued due to an adverse event. Ten serious adverse events occurred: these events were recognized complications of ALS and none were attributed to treatment with RT001.

Signal Amplification By Reversible Exchange (SABRE) boosts NMR signals of various nuclei enabling new applications spanning from magnetic resonance imaging to analytical chemistry and fundamental physics. SABRE is especially well positioned for continuous generation of enhanced magnetization on a large scale, however, several challenges need to be addressed for accomplishing this goal. Specifically, SABRE requires (i) a specialized catalyst capable of reversible H 2 activation and (ii) physical transfer of the sample from the point of magnetization generation to the point of detection (e.g., a high-field or a benchtop NMR spectrometer). Moreover, (iii) continuous parahydrogen bubbling accelerates solvent (e.g., methanol) evaporation, thereby limiting the experimental window to tens of minutes per sample.In this work, we demonstrate a strategy to rapidly generate the best-to-date precatalyst (a compound that is chemically modified in the course of the reaction to yield the catalyst) for SABRE, [Ir(IMes)(COD)Cl] (IMes = 1,3bis-(2,4,6-trimethylphenyl)-imidazol-2-ylidene, COD = cyclooctadiene) via a highly accessible synthesis. Second, we measure hyperpolarized samples using a home-built zero-field NMR spectrometer and study the field dependence of hyperpolarization directly in the detection apparatus, eliminating the need to physically move the sample during the experiment. Finally, we prolong the measurement time and reduce evaporation by presaturating parahydrogen with the solvent vapor before bubbling into the sample. These advancements extend opportunities for exploring SABRE hyperpolarization by researchers from various fields and pave the way to producing large quantities of hyperpolarized material for long-lasting detection of SABRE-derived nuclear magnetization.

Introduction/Aims: Higher urate levels are associated with improved ALS survival in retrospective studies, however whether raising urate levels confers a survival advantage is unknown. In the Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (SURE-ALS) trial, inosine raised serum urate and was safe and well-tolerated. The SURE-ALS2 trial was designed to assess longer term safety. Functional outcomes and a smartphone application were also explored.Methods: Participants were randomized 2:1 to inosine (n = 14) or placebo (n = 9) for 20 weeks, titrated to serum urate of 7-8 mg/dL. Primary outcomes were safety and tolerability. Functional outcomes were measured with the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Mobility and ALSFRS-R were also assessed by a smartphone application.Results: During inosine treatment, mean urate ranged 5.68-6.82 mg/dL.