treatment and management of duchenne muscular dystrophy PDF

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this essay explores duchenne muscular dystrophy as one of the most significant yet less understood noncommunicable disease. this provides a background with information for scholars, patients, and communities...

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Treatment and Management of Duchenne Muscular Dystrophy Student’s Name Institutional Affiliation Location Email Address

Abstract

well as cardiac and pulmonary symptoms. If

This literature review seeks to explore

untreated properly, DMD most DMD victim cannot

Duchenne muscular dystrophy (DMD). DMD is

survive beyond their twenties. Diagnosis entails and

among a rare class of muscle disorders called

analysis of symptoms, clinical examination (muscle

muscular dystrophies. Muscular dystrophies are

biopsy and serum creatine analysis), and genetic

characterized by progressive loss of muscle strength

testing. Treatment options for DMD include

and mass. Dystrophies are genetic disorders. Like

pharmacological management and physical therapy.

other dystrophies, DMD is a genetic disorder caused

These treatments cannot reverse the symptoms or

by inheritance of a defective gene coding for

cure the condition, but improve life quality for the

dystrophin (DMD) – a protein responsible for

victim. Gene therapy is an effective prospective

maintaining muscle strength and mass. DMD is an X-

treatment for the condition. Through gene therapy,

linked disorder inherited maternally. Due to its

DMD can be effectively cured through substitution of

inheritance pattern, DMD typically affects boys while

the defective dystrophin gene (DMD) with a

girls are majorly carriers. Sons of carrier mothers

functional dystrophin gene (DMD).

have 50% chance of suffering from DMD while Keywords: dystrophy, dystrophin, gene, daughters have a 50% chance of being carriers of therapy, carrier, skeletal muscle, cardiac muscle. DMD. DMD symptoms typically appear before the age of six and include muscle mass loss, weakness, as

Introduction

M

Causes of DMD

USCULAR dystrophy

DMD is caused by mutations in the

refers to a category of

dystrophin gene (DMD), which codes for the protein

noncommunicable diseases

dystrophin responsible for muscle strength. A lack of

characterized by the

dystrophin in the muscle cells causes muscle fragility

progressive loss of muscle mass and muscle

and susceptibility to damage, causing the progressive

weakness. The primary symptom for all muscular

muscle weakness and other musculoskeletal

dystrophies is the progressive loss of muscle strength

symptoms. The dystrophin gene (DMD) is X-linked,

[3]. Muscular dystrophies mostly affect males, and

hence is inherited maternally and primarily affects

many of the symptoms of common dystrophies begin

boys. Sons of carrier mothers have a 50% chance of

at childhood. Duchenne muscular dystrophy (DMD)

developing DMD, while the daughters have a 50%

is the most common type of muscular dystrophy,

chance of being carriers [1]. Despite the established

affecting mainly boys [3]. This paper provides a

pattern of inheritance, DMD often occurs in

literature revies of Duchenne muscular dystrophy,

individuals without a family history of the disease.

with a focus on the background of the disease, its

Duchenne occurs with a low prevalence of about 1in

symptoms and treatment options.

every 3600 male births [1].

Background on Disease DMD mainly manifests through symptoms

Symptoms of DMD The typical DMD symptoms often appear

directly related to progressive loss of muscle

before the victims attain the age of six. The first

strength. Such loss of muscle strength mainly affects

symptoms of DMD typically involve muscle

the skeletal and cardiac muscles, leading to

weakness and clumsiness, often in early childhood.

weaknesses associated with movement, posture, and

This leads to delays in developmental milestones

gait [1]. DMD symptoms typically first appear in

involving musculoskeletal system such as sitting,

childhood. The progression of muscle weakness in

walking, and crawling. By early teenage (around 12),

DMD quickly progresses compared to other types of

the muscle weakness becomes pronounced and most

muscular dystrophy.

DMD victims begin using wheelchairs for mobility [1]. The typical DMD symptoms are listed below [1]:

i.

Diagnosis and Treatment

Calf muscle hypertrophy, leading to abnormally larger calves

ii.

The diagnosis of DMD in young boys is

Delayed motor development

based first on the preliminary examination of

(sitting, standing, or walking)

symptoms, family history, and clinical examination.

iii.

Atrophy of skeletal muscles

However, the condition can only be conclusively

iv.

Progressive cardiomyopathy and

confirmed through genetic testing to detect the

cardiomegaly

mutation in the dystrophin gene (DMD) [3]. Clinical

v.

Walking on toes or waddling gait

examination is used to reveal elevated serum creatine

vi.

Using hands to rise up from a lying

phosphokinase (the muscle enzyme) as an indicator

position

of muscle damage. Muscle biopsy is necessary to

Delayed speech and language

microscopically examine muscle tissue [3].

vii.

development Currently, the available treatment for DMD viii.

Impaired cognitive development uses combinational therapy involving

The loss of muscle strength and atrophy

pharmacological agents, supplementation, and

often begins and occurs more severely at the legs and

physical therapy. These treatments can enhance the

the pelvis. Over time, the patient may develop

quality of life for the victims. However, the condition

breathing problems due to the weakening of the lung

cannot be treated with current treatment options [2].

muscles and the diaphragm. Progressive

With these treatments, the prognosis for DMD has

cardiomyopathy may also cause shortness of breath,

been significantly extended, unlike previous years

swelling of limbs, and fatigue. The effects of DMD

before discovery of management options when many

on the heart and the lungs may become life-

patients succumbed to DMD complications in their

threatening, and are the primary causes of death in

twenties [1]. Many DMD patients can currently live

DMD patients. These complications often set in at

longer, productive lives. Physical therapy is used to

around age 20. Therefore, without proper

alleviate some complications of muscle weakness [3].

management, DMD patients are more likely to die in

This helps correct or improve posture, mobility, and

their twenties. The cognitive symptoms of DMD are

gait.

rare and do not worsen as the disease progresses.

Corticosteroids are used for the retardation

restored. With the restoration of dystrophin synthesis

of muscle loss. This slows the worsening of

through the therapeutic DMD, muscle damage and

musculoskeletal symptoms of DMD with time. These

fragility are effectively reversed and DMD is cured

steroids can be administered at the time of diagnosis

[4]. However, gene therapy is a novel treatment

or at the onset of musculoskeletal declines [2]. For

approach that requires further research on the safety,

cardiac symptoms treatments like angiotensin

toxicity, and efficacy of the therapeutic gene.

converting enzyme inhibitors, diuretics, and beta Conclusion blockers are often used to improve heart function [3]. From the foregoing, DMD is a rare muscle Further heart damage may necessitate heart transplant disorder with an incidence of 1 in every 3600 male to avert imminent death. Orthopedic equipment like infants. The condition primary affects males, though braces and wheelchairs are used to enhance patient females can be carriers or mildly affected. DMD is mobility [1]. Respiratory impairments require hereditary, and is caused by a mutation in DMD ventilatory support. causing muscle fragility and damage. The While these current treatments have enabled

conventional treatments are able to extend prognosis

DMD patients to achieve many milestones, they can

of the condition, but cannot cure it. To more effective

still be improved to enhance prognosis and treatment

treat and cure the condition, gene therapy can be

outcomes of the disease. While these treatments slow

applied as a viable treatment option. However, use of

the symptoms and improve quality of life, they

gene therapy to cure DMD requires further research

cannot reverse the course of the disease or cure

on safety and efficacy.

victims [2]. Through gene therapy techniques, DMD REFERENCES can be effectively cured by correcting the defective DMD. Through gene therapy, the normal dystrophin

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Mercuri E, Aartsma-Rus A.

suitable vector such as a lentivirus or a plasmid. This

Duchenne muscular dystrophy.

gene can then be inserted into the patient’s somatic

Nature Reviews Disease Primers.

genome to substitute the defective dystrophin gene

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[4]. By substituting the mutated DMD with a

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