Oral Celecoxib and Ciprofloxacin Slow Functional Decline in ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder characterized by the loss of upper and lower motor neurons, typically leading to death from respiratory failure within two to four years [1]. The complex pathophysiology of the disease involves interacting mechanisms, including neuroinflammation, aberrant protein aggregation such as TAR DNA-binding protein 43 (TDP-43), and dysregulated iron homeostasis [1, 2]. Because single-target therapies have historically yielded limited clinical benefits, researchers are increasingly exploring combination regimens designed to simultaneously modulate multiple neurotoxic pathways [3]. One such strategy pairs the nonsteroidal anti-inflammatory drug celecoxib with the fluoroquinolone antibiotic ciprofloxacin, an oral co-formulation that has demonstrated synergistic neuroprotective effects and improved motor neuron survival in preclinical human induced pluripotent stem cell and animal models [3, 4]. Moving this concept into human subjects, an open-label phase IIa clinical trial involving 15 patients with ALS evaluated this multi-target therapy administered thrice daily for 12 months, demonstrating that the combination was safe, well-tolerated, and significantly altered neural-derived exosomal levels of TDP-43 and the autophagy marker LC3 [5].