ENMC International Workshop: Recent advances in OPMD research: from bench to bedside from the cell to the clinic
Naarden, The Netherlands, June 8-10 2012
During the weekend of 8th to 10th June 2012 twenty clinical, basic scientists funding agency representatives were gathered in Naarden, The Netherlands to discuss clinical and molecular aspects of the late-onset muscular disorder oculopharyngeal muscular dystrophy (OPMD). Delegates were from ENMC member countries (France, Denmark, the Netherlands and the UK) and three non-member countries (United States and Canada). The meeting was the first ENMC workshop dedicated to OPMD.
Background and Aims of the Workshop
Single amino acid repeat expansions are now recognized to be a common cause of human disease. While most of these expansion mutations create increasing lengths of polyglutamine (poly-Q) tracts that cause progressive neurodegenerative disorders, polyalanine tract expansions have also been identified as underlying several monogenic disorders. These disorders are recognized by the presence of salt-resistant insoluble bodies, which results from accumulation of the expanded mutant proteins. The protein aggregation disorders are usually characterized by late onset and progressive neurodegeneration. Among these, a polyalanine tract expansion in the poly(A)-binding protein nuclear 1 (expPABPN1) causes oculopharyngeal muscular dystrophy (OPMD). PABPN1 is ubiquitously expressed and it regulates mRNA stability. Nevertheless it is unclear how is causes muscle weakness OPMD. It is not known why symptoms develop only after midlife and in subsets of skeletal muscles So far, there are no medical options to recover muscle weakness in OPMD.
Outcomes of the Workshop
During the workshop, we discussed:
- current clinical efforts being carried out by the various centers in different countries.
- possible strategies for coordinated approaches to clinical care.
- available model systems for OPMD and their relevance to the disease. therapeutic approaches in OPMD animal model systems and potential treatment approaches in humans.
- recent progress in understanding OPMD disease mechanisms.
- recent advances in comprehension of the molecular function of PABPN1.
- the role of normal aging process in OPMD onset and progression.
- how to set up an international standard for clinical and genetic criteria for OPMD diagnosis.
- how to translate the new discoveries from basic research to realistic therapeutic approaches in patients with OPMD.
How this Will Benefit Patients
Recent progress in identifying molecular mechanisms that are associated with OPMD and the molecular function of PABPN1 offer the prospect of transforming this knowledge to medical options for patients. Retaining close interaction between clinical and molecular teams will speed up speed the development of specific therapeutic approaches for OPMD. OPMD is a rare disorder and therefore international efforts can help in developing new treatments for transfer into the clinic.
A full report of the workshop will be published in Neuromuscular Disorders