Aims

ALS has a complex underlying pathophysiology, indicating that a multi-factorial strategy is needed in order to target multiple pathways.

PrimeC is a novel formulation composed of unique doses of ciprofloxacin and celecoxib, aiming to synergistically inhibit the progression of ALS by addressing three key pathologies; microRNA dysregulation, iron accumulation and neuroinflammation.

Ciprofloxacin, a fluoroquinolone antibiotic, is an iron chelator, and a regulator of Dicer activity, a key enzyme in the microRNA processing pathway.

Celecoxib, an NSAID, regulates neuroinflammation mainly through COX-2 inhibition. Additionally, it has COX-2-independent anti-inflammatory activities.

The objective of the present study was to evaluate the safety and tolerability of PrimeC, and to examine its effects on ALS-related biomarkers

Methods

PrimeC was evaluated clinically in a 12-month, open-label, phase-IIa study in 15 patients with ALS.

Results

Results demonstrate that PrimeC was safe and tolerable in the ALS patient population. These findings were reinforced by encouraging clinical signals when utilizing numerous virtual control models (Origent-prediction-models, ENCALS-survival-prediction model, and PRO-ACT) as a novel approach to control arms in early phase, open-label studies. These results were accompanied by significant changes in ALS-related biomarkers of serum neuron-derived exosomes (NDEs) such as TDP-43 and LC3, indicating a positive biological activity.

Conclusions

The present study demonstrates that PrimeC is safe and well-tolerated. These findings in conjunction with the biological activity observed in biomarkers analysis set the stage for a larger, placebo-controlled study. Importantly, since the aforementioned pathologies are shared between neurodegenerative diseases, we hypothesize that PrimeC may serve as a therapeutic agent for indications, such as Parkinson’s and Alzheimer's.