Exploring physical disability experience in the social context (IPA)

(Case Studies of individuals with a type of Muscular Dystrophy- Duchene)

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TABLE OF CONTENTS

Background of the Study3

Problem of study4

Purpose of the study6

Aim and objectives of the study6

Rationale7

Research Questions7

Scope and Significance of the Study8

Structure of the thesis8

REFERENCES10

BIBLIOGRAPHY12

EXPLORING PHYSICAL DISABILITY EXPERIENCE IN THE SOCIAL CONTEXT (IPA)

Background of the Study

The muscular dystrophies represent a complex group of disorders largely characterized by progressive muscle weakness marked by myofiber fibrosis and necrosis that can affect respiratory and/or cardiac function leading to premature death. These disorders are usually caused by mutations that result in loss or decreased expression of select members of the dystrophin associated glycoprotein complex (DGC). This highly specialized protein network helps to provide the signalling scaffold needed for cell survival and the structural foundation to preserve the integrity of the muscle during contractions (Guglieri et al 2005 63).

A disruption in this complex can cause substantial injury that affects muscle growth, tone, function, and regeneration. Furthermore, loss of one of the members of the DGC can lead to the altered expression other membrane components. Therefore, the preservation of this highly specialized system is necessary for proper muscle development, maintenance and repair upon injury. Interest in the molecular and structural framework of this organ system and its relatedness to muscle disease is suggested to date back to ancient times (Escolar et al 2005 155). Archaeologists have discovered wall paintings that are believed to depict phenotypic characteristics of individuals with motor deficits marked by skeletal deformities and muscle pseudo hypertrophy reminiscent of the clinical features associated with muscular dystrophy (MD). Nevertheless, the foundation for the modern day study of muscular dystrophy is attributed to Duchene and Meryon, who charted the progressive development and pathological features of muscular dystrophy to characterize the degenerative nature of the disease (De Luca et al 2003 459).

Presently, no optimal treatments are available for muscular dystrophy. In the muscular dystrophies, only corticosteroids, which carry a high risk in terms of side effects (bone loss, cataracts, delayed puberty, weight gain, and hypertension), have offered any substantial level of therapeutic intervention. Interestingly, a number of recent studies have suggested a therapeutic potential for the transgenic expression of certain extracellular proteins in the amelioration of key aspects of disease. Specifically, we have demonstrated the biological effects of follistatin (a myostatin inhibitor) to increase myofiber size, muscle strength and body mass in wild type and the mild-phenotype, dystrophin-deficient mdx mouse. Using adeno-associated viral vector (AAV) gene therapy delivery methods, follistatin over expression is well tolerated and has been suggested to have a protective effect on muscle even under dystrophic conditions (Buetler et al 2002 751).

Its efficacy and safety in non human primates has also been evaluated to determine the therapeutic potential of follistatin to be used clinically, as this is an important criterion for human treatment.

Problem of study

Duchene Muscular Dystrophy (DMD) is a progressively lethal muscle wasting disorder that is characterized by continued muscle wasting, cycles of degeneration/regeneration, myofiber fibrosis and necrosis and a resultant loss ...