Elucidating The Synergistic Effect of the PrimeC Combination for Amyotrophic Lateral Sclerosis in iPSC and Mouse Models

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterized by the involvement of multiple interconnected pathways and mechanisms. The complexity of its pathophysiology is reflected in the diverse hypotheses surrounding its underlying causes and progression. Given this intricate interplay of processes, a combination therapy approach offers a promising strategy to target multiple pathways simultaneously. Combination therapies have demonstrated significant success in treating complex diseases such as cancer, Parkinson’s disease, epilepsy, and acquired immunodeficiency syndrome (AIDS), where they aim to achieve synergistic therapeutic effects, reduce drug dosage and associated toxicity, and minimize or delay the development of drug resistance. This approach holds similar potential for ALS, offering a means to address its multifaceted nature more effectively. PrimeC is a novel formulation composed of unique doses of ciprofloxacin and celecoxib. It aims to synergistically inhibit the progression of ALS by addressing key elements of its pathophysiology. The efficacy of PrimeC was compared to its individual active components, celecoxib and ciprofloxacin, and its ability to improve the drug concentration profile and mode of action were assessed. The efficacy of the PrimeC combination was assessed in induced pluripotent stem cell (iPSC)-derived motor neurons that model ALS. Motor neurons treated with the PrimeC combination exhibited higher survival rates than those treated with the individual compounds. These results were reinforced by a drug concentration profiling study in rodents showing that the combination of celecoxib and ciprofloxacin had a synergistic effect, as the addition of celecoxib increased the concentration of ciprofloxacin in the brain tissue and serum of rodents. In summary, our data suggests that combination therapy can be a beneficial approach for treating ALS. PrimeC has the potential to be used for the treatment of ALS, based on the positive results obtained from our studies.