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Muscular Dystrophy Treatment in India

What Is Muscular Dystrophy ?

Muscular Dystrophy (MD) a genetic (inherited) disorder of muscles. Muscular dystrophy causes the muscles in the body to become very weak. The muscles break down and are replaced with fatty deposits over time.
Some forms of Muscular Dystrophy are seen in infancy or childhood, while others may not appear until middle age or later.
About 1 out of every 3,500 to 5000 boys is born with Muscular Dystrophy.Other health problems commonly associated with muscular dystrophy are:
Heart muscle problem or Cardiomyopathy

Scoliosis – a lateral or sideways, curvature and rotation of the back bones (vertebrae), giving the appearance that the person is leaning to one side Obesity

Definition of Gene :

Every cell in any living being has a nucleus built up of numerous pieces of information. These particles are called genes, and comprise a set of instructions that determine what the organism is like, its appearance, how it survives, and how it behaves in its environment. Many genes make a chromosome. Many chromosomes make a nucleus, one of which governs each cell in a body.

What is called Genetic or Inherited Disorders :

A Genetic or Inherited Disorders is an illness caused by abnormalities in Genes or Chromosomes. Variations within the DNA sequence of a particular Gene affect its function, and may cause or predispose an individual a particular disease which transmitted with the generations.

Different type of Muscular Dystrophy :

Duchenne’s Muscular Dystrophy (DMD)

Becker’s Muscular Dystrophy (BMD)

Emery- Dreifuss Dystrophy (EDD)

Facioscapulohumeral Dystrophy (FHD)

Scapuloperoneal Syndrome

Oculopharyngeal Dystrophy

Congenital Muscular Dystrophies

Kearns-Sayre Syndrome

Myotonic Dystrophy

Limb-Girdle Muscular Dystrophies (LGMD)

Duchenne’s Muscular Dystrophy (DMD) :

Duchenne muscular dystrophy is caused by an X-linked recessive gene. “X-linked” means that the gene causing the trait or the disorder is located on the X chromosome. Genes on the X chromosome can be recessive or dominant, and their expression in females and males is not the same because the genes on the Y chromosome do not exactly pair up with the genes on the X. X-linked recessive genes are expressed in females only if there are two copies of the gene (one on each X chromosome). However, for males there only needs to be one copy of an X-linked recessive gene in order for the trait or disorder to be expressed. For example, a woman can carry a recessive gene on one of the X chromosomes unknowingly, and pass it on to a son, who will express the trait or disease.

Symptoms of DMD :

a) Symptoms usually appear in male children before age 6 and may be visible in early infancy

b) Early signs may include enlargement of calf and deltoid muscles, low endurance, and difficulties in standing unaided or inability to ascend staircases

c) Gower’s manoeuvre (See next slide)

d) Contractures of hip, knees & ankles become severe when relatively untreated child spends much of the day in wheelchair

e) Hips & Knees are locked at 90 degrees & feet turn downward & inward in an exaggerated position of equinovarus

f) With development of severe scoliosis, resp fn becomes compromised

g) Cardiac inv : degeneration & fibrosis of posterolateral wall of lt.ventricle

h) Mental impairment is common. IQ is 1 SD below the mean

Gower’s Maneuver:

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Diagnosis of DMD :

a) Heart testing – electrocardiography (ECG)

b) Muscles charting to diagnose activity and efficiency of the muscles

c) Mutation analysis of DNA testing (Genetic Tests: Exon skipping) and Muscle Biopsy for Dystrophin level from peripheral blood leukocytes which confirms the deletion of dystrophin gene

d) 30 % of pts in whom deletion is not found , Muscle Biopsy is required to establish absence of dystrophin

e) Creatine phosphokinase (CPK) a simple blood test. When the total CPK level is very high, it usually means there has been injury or stress to muscle tissues

f) Western blot analysis of muscle biopsy to find reduced amount or abnormal size of dystrophin

g) Electromyography (EMG) nerve testing

Treatment options for DMD :

a) Physical Therapy : aim : to keep joints as loose as possible. Commenced at 3-4 yrs of age , when parents are taught to stretch child’s heel cords, hip flexors, iliotibial bands on daily basis

b) Night splints can be considered

c) Bracing : appropriate use of bracing – delay child’s progression to wheelchair by approx 2yrs

d) Surgery : Reconstructive surgery of the leg often accompanies bracing. The purpose : to keep leg extended & prevent contractures of iliotibial bands & hip flexors

e) Percutaneous tenotomies of Achilles tendon, knee flexors, hip flexors and iliotibial bands

f) Pharmacological : Prednisolone improves muscle strength & Deflazacort-Synthetic Steroid

Why Stem Cell therapy may be an option for Muscular Dystrophy Treatment in India?

There are half a dozen drugs in clinical trial Stage II or Stage III. This means that they are still a few years away from commercial availability. Today’s DMD patient must survive in at least moderate severity stage but not sever state in order to qualify for the use of future drugs. To enable as many DMD patient as possible to remain in treatable stage the only option left is Stem Cell therapy. They may be experimental and clinical study stage but they may offer benefit within three months at an affordable cost compare to what the new therapies will cost. The main stem-cell-based approaches currently being investigated are:

Producing healthy muscle fibres: Clinicians hope that if stem cells without the genetic defect that causes DMD can be delivered to patients’ muscles, they may generate working muscle fibres to replace the patient’s damaged ones.

Reducing inflammation: In muscular dystrophy damaged muscles become very inflamed. This inflammation speeds up muscle degeneration. Clinicians believe certain types of stem cells may release chemicals that reduce inflammation, slowing the progress of the disease.

Muscular Dystrophy Treatment

Counseling
Assessment and Muscle charting
Genetic Diagnostic
Physiotherapy
Assistive devices
SCT Regenerative Medical Intervention(Experimental)
Research work (Clinical Case Studies)