Can memantine and/or trazadone slow ALS progression? Nope. A brand new large randomized study out by Pal and colleagues @TheLancetNeuro. Can we test multiple drugs at once by sharing a placebo or control arm? Yep. Key Points: - The authors point that ALS and motor neuron disease are progressive and to date incurable neurodegenerative diseases. - Riluzole is used globally as a treatment. - Edaravone, masitinib, AMX0035 (sodium phenylbutyrate+tauroursodeoxycholic acid), and tofersen recently tested. - They point out only tofersen approved in Europe. - Their trial was the Motor Neuron Disease Systematic Multi-Arm Adaptive Randomised Trial (MND SMART). - Double-blind, placebo-controlled and adaptive. - Like the HEALEY platform trials in the US, the MND SMART uses 'simultaneous definitive evaluation of multiple treatment groups against a single control group; and the design allows to adapt and possibly test multiple approaches.' - The trial was negative. My take: It is really cool to see more compounds tested faster by using shared control groups and an adaptive design. This trial was negative meaning both drugs had no effect on disease progression. I think we have to ask 'why' when we select compounds to trial, especially since animal data does not always recapitulate human data. Memantine targets excitotoxicity and calcium-mediated death of neurons. It is widely used for memory and thinking in diseases like Alzheimer's, however with very small effect. Trazodone may impact the stress on cells and and may also possibly impact misfolded proteins. Most people in the USA use trazodone for sleep, mood and other symptoms. As we test more drugs it will be terrific if we can come up with better techniques to predict which ones may have a meaningful impact on human diseases like ALS. thelancet.com/journals/laneu… #ALS #Motorneurondisease #LouGehrig #parkinson #Alzheimers @bsw5020