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New research shows that variants in two FTD–ALS risk genes impair the functioning of the endolysosomal pathway, leading to pathological intracellular accumulation of TDP43 protein.
In this Perspective, the authors discuss the importance of performing well-designed observational studies on Alzheimer disease. They highlight novel approaches to enhance causal inference and discuss ways in which observational data can provide a bridge between preclinical findings and clinical trials.
In this Review, Vezzani et al. discuss how dysregulation of key astrocyte functions — gliotransmission, cell metabolism and immune function — contribute to the development and progression of hyperexcitability in epilepsy and consider strategies to mitigate astrocyte dysfunction.
Following successful clinical trials of a gene therapy for Leber hereditary optic neuropathy, Pitceathly and colleagues discuss progress towards genetic therapies for other primary mitochondrial diseases. They highlight advances in DNA editing technologies and offer their view on obstacles to clinical application.
In this Review, Eichmüller and Knoblich discuss how human brain organoids can recapitulate the unique processes that occur in human brain development and how they can complement classical approaches to revolutionize research into neurological diseases.
Most cases of Alzheimer disease (AD) have a complex aetiology, probably involving multiple genetic and environmental factors. In this Review, the authors discuss how various environmental AD risk factors could induce epigenetic modifications of key AD-associated genes and pathways.
In the first two phase II trials of therapies that target α-synuclein to treat Parkinson disease, the primary endpoints were not met. However, the limitations of these studies need to be addressed in future trials and alternative approaches to targeting α-synuclein should be pursued before α-synuclein is discounted as a target.
Currently, the anti-CD20 monoclonal antibody ocrelizumab is the only approved treatment for primary progressive multiple sclerosis (PPMS). However, a new study suggests that other immunomodulatory disease-modifying therapies that are often used to treat relapsing forms of multiple sclerosis could be effective in people with PPMS who have evidence of active inflammatory disease.