Cure CMD, a Patient-Centered Organization: Pivotal Role to Help Move Emerging Therapeutics into Clinical Practice for the Congenital Muscular Dystrophies

The mission of Cure CMD is to promote research directed to find a cure for the Congenital Muscular Dystrophies (CMD). Cure CMD, a patient advocacy organization, was founded in 2008 by three parents whose children were affected by understudied forms of CMDs. Just before the end of the 20th century, the genes and coded proteins responsible for the clinicopathological presentations of CMD started to be revealed. Merosin or laminin 211 was the first dysfunctional protein identified in western cases of CMD. Later, a lack of another protein, collagen VI, was found to cause a different type of CMD. Today, it is recognized that the five main subtypes of CMD involve proteins in four locations of the muscle cell: the extracellular matrix (ECM) where laminin 211 and collagen VI reside (LAMA2-CMD and ColVI-CMD); the ECM-sarcoplasm interface where the á-dystroglycan is the affected protein, either, as a consequence of mutations in its coding gene (primary Dystroglycanopathy) or mutations in various glycosyltransferase proteins (secondary Dystroglycanopathies); the sarcoplasmic reticulum, location of the SEPN1 protein (Selenon or SEPN1-CMD); and the intranuclear membrane where the mutated protein lamin A/C provokes the CMD subtype (LMNA or L-CMD).The CMDs are a clinically and genetically heterogeneous group of NMDs. The symptoms are evident at birth or before the second birthday. They present progressive weakness and hypotonia and share characteristic biopsy findings. Several disease-related complications include nutritional deficiencies due to feeding difficulties, joint contractures, and respiratory insufficiency. In some cases, heart complications and cognitive impairment, are also present. Promising developments in biotechnology and a deeper understanding of the underlying pathophysiological mechanisms responsible for the different CMD types have facilitated design potential therapeutic schemes targeted at molecular, and biochemical pathways. Through close collaboration with researchers, clinicians, patients, families, dedicated volunteers, other foundations and donors, Cure CMD, has achieved significant impact in its first decade as a nonprofit organization: launched two clinical trials; completed a five-year natural history study with the NIH to characterize clinical trial endpoints; grew the Congenital Muscle Disease International Registry (CMDIR) with approximately 3,000 registrants worldwide and, funded over $2 million in research grants. We will describe tools and programs Cure CMD has to offer to accelerate the “bench-to-bedside” translation of therapies.