Objective: This study aimed to evaluate the safety and tolerability of a fixed-dose co-formulation of ciprofloxacin and celecoxib (PrimeC) in patients with amyotrophic lateral sclerosis (ALS), and to examine its effects on disease progression and ALS-related biomarkers. Methods: In this proof of concept, open-label, phase IIa study of PrimeC in 15 patients with ALS, participants were administered PrimeC thrice daily for 12 months. The primary endpoints were safety and tolerability. Exploratory endpoints included disease progression outcomes such as forced vital capacity, revised ALS functional rating scale, and effect on algorithm-predicted survival. In addition, indications of a biological effect were assessed by selected biomarker analyses, including TDP-43 and LC3 levels in neuron-derived exosomes (NDEs), and serum neurofilaments. Results: Four participants experienced adverse events (AEs) related to the study drug. None of these AEs were unexpected, and most were mild or moderate (69%). Additionally, no serious AEs were related to the study drug. One participant tested positive for COVID-19 and recovered without complications, and no other abnormal laboratory investigations were found. Participants' survival compared to their predictions showed no safety concerns. Biomarker analyses demonstrated significant changes associated with PrimeC in neural-derived exosomal TDP-43 levels and levels of LC3, a key autophagy marker. Interpretation: This study supports the safety and tolerability of PrimeC in ALS. Biomarker analyses suggest early evidence of a biological effect. A placebo-controlled trial is required to disentangle the biomarker results from natural progression and to evaluate the efficacy of PrimeC for the treatment of ALS. Summary for social media if publishedTwitter handles: @NeurosenseT, @ShiranZimri•What is the current knowledge on the topic? ALS is a severe neurodegenerative disease, causing death within 2–5 years from diagnosis. To date there is no effective treatment to halt or significantly delay disease progression.•What question did this study address? This study assessed the safety, tolerability and exploratory efficacy of PrimeC, a fixed dose co-formulation of ciprofloxacin and celecoxib in the ALS population.•What does this study add to our knowledge? This study supports the safety and tolerability of PrimeC in ALS, and exploratory biomarker analyses suggest early insight for disease related-alteration.•How might this potentially impact the practice of neurology? These results set the stage for a larger, placebo-controlled study to examine the efficacy of PrimeC, with the potential to become a new drug candidate for ALS.

Shiran Salomon-Zimri

Avital Pushett

Niva Russek-Blum

Ruben P. A. Van Eijk

Nurit Birman

Beatrice Abramovich

Erez Eitan

Katya Elgrart

Danielle Beaulieu

David L. Ennist

James D. Berry

Sabrina Paganoni

Jeremy M. Shefner

Vivian E. Drory

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

肌萎缩侧索硬化和额颞叶变性是一项令人兴奋的新举措。它代表了《肌萎缩侧索硬化》杂志的及时扩展，以应对 ALS 和额颞叶痴呆之间的临床、影像学病理和遗传重叠。扩展后的期刊对与运动神经元疾病相关的广泛问题的研究提供了出色的报道，特别是 ALS（LOU GEHRIG 病）和与额颞叶退化相关的认知衰退。该杂志还涵盖了与这些核心疾病相关的神经轴疾病。

The journal "Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration" is an exciting new initiative that represents a timely expansion of the journal "Amyotrophic Lateral Sclerosis" to address the clinical, imaging pathological, and genetic overlaps between ALS and frontotemporal dementia. The expanded journal provides excellent coverage of a wide range of issues related to motor neuron diseases, with a particular focus on ALS (Lou Gehrig's disease) and cognitive decline associated with frontotemporal degeneration. Additionally, the journal covers research related to neuroaxial diseases associated with these core conditions.

《Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration》是一个令人兴奋的新期刊，旨在扩展《肌萎缩侧索硬化》杂志，以应对肌萎缩侧索硬化（ALS）和额颞叶痴呆之间的临床、影像学病理和遗传重叠。该期刊提供了对与运动神经元疾病相关的广泛问题的深入研究，特别关注ALS（又称卢·盖里希病）及其与额颞叶退化相关的认知衰退。此外，期刊还涵盖了与这些核心疾病相关的神经轴疾病的研究。

Combination of ciprofloxacin/celecoxib as a novel therapeutic strategy for ALS

环丙沙星/塞来昔布联合治疗作为ALS新型治疗策略

Category	Quartile
医学	4
医学, 临床神经病学	4

Combination of ciprofloxacin/celecoxib as a novel therapeutic strategy for ALS

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Journal Info

Category	Quartile
CLINICAL NEUROLOGY	2