DUCHENNE MUSCULAR DYSTROPHY

Genetic Problems Associated with Duchenne Muscular Dystrophy, Possible Cures and Hindrances in Expression of the Therapeutic Gene Product

Abstract

Duchenne Muscular Dystrophy, which is a combination of immunological complications and genetic disorder, occurs once in every thirty six thousand to six thousand live male births can prove to be fatal for patients suffering from it. Extensive research has been carried out on the down-regulation of the immune cell infiltration into dystrophic muscle tissue and acceptance of therapeutic gene product by the host's immune system. However a breakthrough in anti-self response in auto immunity of the host's system and organ grafting needs to be achieved in order to find a cure to this disease.

Table of Contents

Abstracti

Introduction1

Discussion2

Duchenne Muscular Dystrophy2

Immunological Complications Associated With DMD3

Current Treatments for DMD4

Ongoing Research for DMD Treatment5

Potential approaches for a cure - gene therapy6

Obstacles to Gene Therapy6

Conclusion7

LITERATURE CITED9

APPENDIX11

Genetic Problems Associated With Duchenne Muscular Dystrophy, Possible Cures and Hindrances in Expression of the Therapeutic Gene Product

Introduction

A group of genetic disorders linked with progressive muscle weakness and wasting is referred to as muscular dystrophies. The main cause of muscular dystrophy is defect in muscle protein. Not only does this disease affect mobility, it can also lead to destruction of various systems of the body including the cardiac system, respiratory system and the nervous system. The destruction of the respiratory system is caused by wasting of muscle in the diaphragm. A very severe and frequently occurring type of muscular dystrophy is the Duchenne muscular dystrophy (DMD). DMD affects approximately one in thirty six hundred to six thousand live male births per annum. DMD is a direct consequence of the mutation of the essential muscle structural protein i.e. the X-linked gene coding for dystrophin protein. Gene therapy has been considered to be a potential way to cure DMD since many years now. Due to the generation of high capacity adenoviral (HC-Ad) vectors, the transfer of large, full length dystrophin cDNA of about 11 kb has become possible. These vectors are depleted of all viral genes (Alba et. al, 2005). Though this vector has an advantage over the previously used adenoviral vectors, however, the immune response of the host to the therapeutic gene product and vector is considered to be the main barrier to successful dystrophin gene transfer. Transient blockage of the immune system stimulation at the time of gene delivery is one of the various methods that have been tried in order to overcome the problem of vector and gene product rejection (Jiang et.al, 2004). Immunological complications such as massive infiltration of T cells that promote the pathology of the disease are linked to untreated dystrophic muscle tissue (Farini et. al, 2007). Therefore, auto immune like reactions in the damaged muscles are an important factor in the development of the disease besides the genetic mutations that lead to the pathogenicity of DMD.

The subsequent pages discuss various researches carried out to:

Understand the host anti-dystrophin immune responses to HC-Ad vector mediated dystrophin cDNA transfer in dystrophic mdx mouse, and eliminate ...