Dr. Vered Raz
Oculopharyngeal muscular dystrophy (OPMD) is a late onset myopathy. Patients have muscle weakness that typically starts after midlife affecting eyelid dropping (ptosis), swallowing and walking difficulties. Muscle weakness is progressive and gradually most skeletal muscles are affected. The disease is caused by alanine expansion mutations in the gene encoding for poly(A)-binding protein nuclear 1 (PABPN1). The expanded PABPN1 accumulates in the cell nucleus and forms insoluble aggregates, the hallmark of the disease. Recent studies, including ours, suggest that limited availability of functional PABPN1 cause muscle weakness in OPMD patients and also in the elderly. We found that the expression of PABPN1 significantly decreases in OPMD muscle and in muscles from the elderly. PABPN1 is a multifunctional regulator of RNA metabolism. This opens a novel role for RNA metabolism is muscle aging and in OPMD.
Currently, there are no medical options to prevent or delay muscle weakness in OPMD. We investigate possibilities to restore PABPN1 expression in OPMD and in down-regulated conditions. We focus on the regulation of PABPN1 protein accumulation by the ubiquitin proteasome system.