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The SOD1 mouse – 10 years later

It has been more than 10 years since two seminal papers by Ludolph et al (2007) and Scott et al (2008) have introduced recommendations for the use of an SOD1 mutant mouse strain to discover new treatments against amyotrophic lateral sclerosis (ALS).
 
We, as well as many of our colleagues, have repeatedly referred to the work done by the ALS Therapy Development Institute that resulted in a striking conclusion – if the study was designed and conducted under the most stringent quality standards, most experimental treatments failed to show any significant efficacy. What was even worse, when re-tested under the new quality standards, essentially all previously “effective” treatments have turned into “negative”.
 
Over the past 10 years, we have referred to these findings in the context of discussing new claims of efficacy for novel agents that represented exciting scientific concepts but failed to follow the quality standards and recommendations mentioned above. And, conversely, we were happy to see papers in this field that at least acknowledge the existence of these guidelines! 
 
Marcel Maier and colleagues from Neurimmune Therapeutics AG have published a paper describing the ability of a human-derived antibody to target misfolded SOD1 and to ameliorate motor symptoms in mouse models of ALS, including the mouse strain overexpressing the SOD1G93A mutation. Even though there is a room for improvement (well, old man grunting…), the sample size is certainly in line with the recommendations, subjects are litter- and sex-balanced, handling and analysis were blinded, etc. The results presented by Maier et al may indeed be a breakthrough discovery and we hope that the Neurimmune team will be able to complement the robust effects during the pre-symptomatic window by adding evidence on the efficacy of this antibody in later symptomatic phases. Given that Steve Perrin of the ALS TDI is one of the co-authors, we do hope that the findings described in the paper signify a real chance for the ALS patients!
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