March 26, 2026

@michaelokun

A new combination therapy in ALS: Did PrimeC move the needle? Combination therapy means using two medications together to target multiple disease pathways at the same time. Cudkowicz and colleagues describe in a new paper in JAMA Neurology the results of the PARADIGM randomized clinical trial testing PrimeC in ALS. The results were encouraging, however the trial was not powered for efficacy. Key Points: - PrimeC, a combination of celecoxib and ciprofloxacin, was safe and well tolerated over 18 months w/ side effects mostly mild to moderate. - Continuous treatment showed signals of slower functional decline and reduced risk of major ALS complications such as hospitalization, respiratory failure or death. - Biomarker changes suggested engagement of key ALS pathways including iron regulation, inflammation and microRNA biology. My take: This is an encouraging and thoughtful study. ALS is a complex disease and targeting multiple pathways simultaneously makes biological sense. The results do not yet provide definitive proof of benefit, however the signals across function, complications and biomarkers suggest we may be moving in the right direction. Can they get to meaningful clinical change? Here are 5 take home points that resonated w/ me: 1- ALS may likely requires multi target approaches rather than single pathway therapies. 2- Safety matters and this study supports that combination strategies can be tested carefully in this population. 3- Slowing progression even modestly could translate into meaningful time and function for folks living w/ ALS. 4- Biomarkers such as microRNAs and iron markers may help us understand whether a therapy is truly engaging disease biology. 5- The future of ALS treatment may depend on combining therapies, timing them correctly and matching them to the right folks. https://jamanetwork.com/journals/jamaneurology/fullarticle/2846474 #parkinson #michaelokun #fixelinstitute