CAG Triplet Repeat Diseases: Common Principles and Unique Mechanisms

The CAG Triplet Repeat Disorders are a group of largely untreatable, heritable neurological disorders, which result from an expansion in a CAG trinucleotide repeat in mutant genes. They include Huntington's disease (HD), spinal and bulbar muscular atrophy (SBMA, Kennedy's disease), several spinocerebellar ataxias, and dentatorubropallidoluysian atrophy (DRPLA). Extended CAG repeats in the coding regions of genes result in abnormally long polyglutamine tracts in the mutant proteins. Marked similarities in the underlying genetics and the neurological symptoms suggest common pathogenic mechanisms. Exciting new efforts to unravel these mechanisms have recently been made in the area of proteostasis research, which is of high relevance to understanding proteopathies like CAG repeat diseases. To delineate the networks of cellular homeostasis in their entirety "-omics" approaches have moved into the focus and have unraveled surprising new connections between the molecules involved in disease. Seeding and spreading of misfolded protein species have recently been recognized as perhaps highly relevant to pathogenesis. Connected to these phenomena, innovative technologies to identify relevant targets, disease markers and effective therapeutics are in development. To increase the pace of molecular discovery and to accelerate translation into the clinic, a multidisciplinary effort is required.

The 2017 Gordon Research Conference on CAG Triplet Repeat Disorders and the associated Gordon Research Seminar (GRS) will gather young investigators and established senior scientists to deliver thought-provoking lectures on the cutting edge of science. In keeping with the Gordon Research Conference tradition, there will be ample time for structured discussions led by peers and for informal discussion and social interaction. Strong emphasis is placed on training and mentoring, and time will be devoted to career issues. All participants are required to submit posters, based on which invitations for short talks will be issued. Priority will be given to women, minorities and persons with disabilities when selecting speakers.