To coincide with the 200th anniversary of the publication of An Essay on the Shaking Palsy by James Parkinson, Goedert and Compston explore the origins of the eponym 'Parkinson's disease'. Although Jean-Martin Charcot is often credited with introducing the name in the 1880s, it can actually be traced back to an 1865 publication by William Rutherford Sanders.

In this Review, a group of experts in fragile X syndrome analyses why the considerable drug development effort based on robust preclinical findings describing the mechanisms underlying this neurodevelopmental disorder has failed to translate into effective treatment and offers possible solutions to improve clinical trial design and therapeutic approaches.

The contribution of genomics to drug discovery and development so far has not yet lived up to the initial high expectations. Goldstein and colleagues discuss the reasons for the limited progress and review how recent advances — particularly in oncology and rare genetic diseases — may enable precision medicine strategies to harness the therapeutic potential of genomic knowledge.

A nucleotide repeat expansion in C9orf72 is a common genetic cause of neurodegenerative disorders. Here, the authors provide insight into the molecular mechanism by which this repeat undergoes Repeat-Associated Non-AUG (RAN) translation, implicating the integrated stress response and eIF2α phosphorylation.