Mutations in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS). Accumulating evidence implicates astrocytes as important non‐cell autonomous contributors to ALS pathogenesis, although the potential deleterious effects of astrocytes on the function of motor neurons remains to be determined in a completely humanized model of C9orf72‐mediated ALS. Here, we use a human iPSC‐based model to study the cell autonomous and non‐autonomous consequences of mutant C9orf72 expression by astrocytes. We show that mutant astrocytes both recapitulate key aspects of C9orf72‐related ALS pathology and, upon co‐culture, cause motor neurons to undergo a progressive loss of action potential output due to decreases in the magnitude of voltage‐activated Na+ and K+ currents. Importantly, CRISPR/Cas‐9 mediated excision of the C9orf72 repeat expansion reverses these phenotypes, confirming that the C9orf72 mutation is responsible for both cell‐autonomous astrocyte pathology and non‐cell autonomous motor neuron pathophysiology.

In the context of (digital) human–machine interaction, people are increasingly dealing with artificial intelligence in everyday life. Through this, we observe humans who embrace technological advances with a positive attitude. Others, however, are particularly sceptical and claim to foresee substantial problems arising from such uses of technology. The aim of the present study was to introduce a short measure to assess the Attitude Towards Artificial Intelligence (ATAI scale) in the German, Chinese, and English languages. Participants from Germany (N = 461; 345 females), China (N = 413; 145 females), and the UK (N = 84; 65 females) completed the ATAI scale, for which the factorial structure was tested and compared between the samples. Participants from Germany and China were additionally asked about their willingness to interact with/use self-driving cars, Siri, Alexa, the social robot Pepper, and the humanoid robot Erica, which are representatives of popular artificial intelligence products. The results showed that the five-item ATAI scale comprises two negatively associated factors assessing (1) acceptance and (2) fear of artificial intelligence. The factor structure was found to be similar across the German, Chinese, and UK samples. Additionally, the ATAI scale was validated, as the items on the willingness to use specific artificial intelligence products were positively associated with the ATAI Acceptance scale and negatively with the ATAI Fear scale, in both the German and Chinese samples. In conclusion we introduce a short, reliable, and valid measure on the attitude towards artificial intelligence in German, Chinese, and English language.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of phase II, phase II/III and phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15000 people with amyotrophic lateral sclerosis. 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.