Duchenne muscular dystrophy (DMD) is the most common childhood Iorm oI muscular

dystrophy, becoming clinically evident when a child begins walking. Patients typically require a
wheelchair by age 10 to 12 and die in their late teens to early 20s,
|15|
though some people with
Duchenne muscular dystrophy are now living to age 40 and beyond.
|citation needed|
In the early
1990s, researchers identiIied the gene Ior the protein dystrophin which, when absent, causes
DMD. The amount oI dystrophin correlates with the severity oI the disease (i.e. the less
dystrophin present, the more severe the phenotype). Since the gene is on the X chromosome, this
disorder aIIects primarily males, and Iemales who are carriers have milder symptoms. Sporadic
mutations in this gene occur Irequently, accounting Ior a third oI cases. The remaining two-thirds
oI cases are inherited in a recessive pattern.
Dystrophin is part oI a complex structure involving several other protein components. The
"dystrophin-glycoprotein complex" helps anchor the structural skeleton (cytoskeleton) within the
muscle cells, through the outer membrane (sarcolemma) oI each cell, to the tissue Iramework
(extracellular matrix) that surrounds each cell. Due to deIects in this assembly, contraction oI the
muscle leads to disruption oI the outer membrane oI the muscle cells and eventual weakening
and wasting oI the muscle.
|4|

Duchenne muscular dystrophy

Duchenne muscular dystrophy is an inherited disorder that involves rapidly worsening muscle
weakness.
Causes
Duchenne muscular dystrophy is a rapidly-worsening Iorm oI muscular dystrophy. Other
muscular dystrophies (including Becker's muscular dystrophy) get worse much more slowly.
Duchenne muscular dystrophy is caused by a deIective gene Ior dystrophin (a protein in the
muscles). However, it oIten occurs in people without a known Iamily history oI the condition.
Because oI the way the disease is inherited, males are more likely to develop symptoms than are
women. The sons oI Iemales who are carriers oI the disease (women with a deIective gene but no
symptoms themselves) each have a 50 chance oI having the disease. The daughters each have a
50 chance oI being carriers.
Duchenne muscular dystrophy occurs in approximately 1 out oI every 3,600 male inIants.
Because this is an inherited disorder, risks include a Iamily history oI Duchenne muscular
dystrophy.
Symptoms
Symptoms usually appear beIore age 6 and may appear as early as inIancy. They may include:
O Fatigue
O Mental retardation (possible, but does not worsen over time)
O Muscle weakness
4 Begins in the legs and pelvis, but also occurs less severely in the arms, neck, and
other areas oI the body
4 DiIIiculty with motor skills (running, hopping, jumping)
4 Frequent Ialls
4 Rapidly worsening weakness
O Progressive diIIiculty walking
4 Ability to walk may be lost by age 12
By age 10, the person may need braces Ior walking. By age 12, most patients are conIined to a
wheelchair.
ams and Tests
A complete nervous system (neurological), heart, lung, and muscle exam may show:
O Abnormal heart muscle (cardiomyopathy)
O Congestive heart Iailure or irregular heart rhythm (arrhythmias) -- rare
O DeIormities oI the chest and back (scoliosis)
O Enlarged calI muscles, which are eventually replaced by Iat and connective tissue
(pseudohypertrophy)
O Loss oI muscle mass (wasting)
O Muscle contractures in the heels, legs
O Muscle deIormities
O Respiratory disorders, including pneumonia and aspiration oI Iood or Iluid into the lungs
(in late stages oI the disease)
Tests may include:
O Electromyography (EMG)
O Genetic tests
O Muscle biopsy
O Serum CPK
Treatment
There is no known cure Ior Duchenne muscular dystrophy. Treatment aims to control symptoms
to maximize quality oI liIe. Gene therapy may become available in the Iuture.
Activity is encouraged. Inactivity (such as bedrest) can worsen the muscle disease. Physical
therapy may be helpIul to maintain muscle strength and Iunction. Orthopedic appliances (such as
braces and wheelchairs) may improve mobility and the ability to care Ior yourselI.
Support Groups
You can ease the stress oI illness by joining a support group where members share common
experiences and problems. See muscular dystrophy - support group. The Muscular Dystrophy
Association is an excellent source oI inIormation on this disease.
Outlook (Prognosis)
Duchenne muscular dystrophy leads to quickly worsening disability. Death usually occurs by age
25, typically Irom lung disorders.
Possible Complications
O Cardiomyopathy
O Congestive heart Iailure (rare)
O DeIormities
O Heart arrhythmias (rare)
O Mental impairment (varies, usually minimal)
O Permanent, progressive disability
4 Decreased mobility
4 Decreased ability to care Ior selI
O Pneumonia or other respiratory inIections
O Respiratory Iailure
hen to Contact a Medical Professional
Call your health care provider iI:
O Your child has symptoms oI Duchenne muscular dystrophy
O Symptoms worsen, or new symptoms develop, particularly Iever with cough or breathing
diIIiculties
Prevention
Genetic counseling is advised iI there is a Iamily history oI the disorder. Duchenne muscular
dystrophy can be detected with about 95 accuracy by genetic studies perIormed during
pregnancy.
Alternative Names
Pseudohypertrophic muscular dystrophy; Muscular dystrophy - Duchenne type
#eferences
Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Muscular dystrophies. In: Kliegman RM,
Behrman RE, Jenson HB, Stanton BF. elson Textbook of Pediatrics. 18th ed. Philadelphia,
Pa:Saunders Elsevier; 2007:chap 608.
&pdate Date: 3/9/2010
Updated by: Neil K. Kaneshiro, MD, MHA, Clinical Assistant ProIessor oI Pediatrics,
University oI Washington School oI Medicine; Daniel B. Hoch, PhD, MD, Assistant ProIessor oI
Neurology, Harvard Medical School, Department oI Neurology, Massachusetts General
Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
Duchenne muscular dystrophy (DMD) is a recessive X-linked Iorm oI muscular dystrophy,
which results in muscle degeneration, diIIiculty walking, breathing, and death. The incidence is 1
in 3,000 boys.
|1|
Females and males are aIIected, though Iemales are rarely aIIected and are more
oIten carriers. The disorder is caused by a mutation in the dystrophin gene, located in humans on
the X chromosome (Xp21). The dystrophin gene codes Ior the protein dystrophin, an important
structural component within muscle tissue. Dystrophin provides structural stability to the
dystroglycan complex (DGC), located on the cell membrane.
Symptoms usually appear in male children beIore age 5 and may be visible in early inIancy.
Progressive proximal muscle weakness oI the legs and pelvis associated with a loss oI muscle
mass is observed Iirst. Eventually this weakness spreads to the arms, neck, and other areas. Early
signs may include pseudohypertrophy (enlargement oI calI and deltoid muscles), low endurance,
and diIIiculties in standing unaided or inability to ascend staircases. As the condition progresses,
muscle tissue experiences wasting and is eventually replaced by Iat and Iibrotic tissue (Iibrosis).
By age 10, braces may be required to aid in walking but most patients are wheelchair dependent
by age 12. Later symptoms may include abnormal bone development that lead to skeletal
deIormities, including curvature oI the spine. Due to progressive deterioration oI muscle, loss oI
movement occurs, eventually leading to paralysis. Intellectual impairment may or may not be
present but iI present, does not progressively worsen as the child ages. The average liIe
expectancy Ior patients aIIlicted with DMD varies Irom late teens to early to mid 20s. There
have been reports oI a Iew DMD patients surviving to the age oI 40, but this is extremely
rare.
|citation needed|

Contents
hlde
O 1 lncldence/prevalence
O 2 Lponym
O 3 aLhogenesls
O 4 SympLoms
O 3 Slgns and LesLs
O 6 ulagnosls
4 61 unA LesL
4 62 Muscle blopsy
4 63 renaLal LesLs
O 1reaLmenL
4 1 rognosls
4 2 hyslcal Lherapy
4 3 Mechanlcal venLllaLory/resplraLlon asslsLance
O CccupaLlonal and hyslcal 1herapy
4 1 SpllnLlng and CrLhoses
4 2 Manual Muscle 1esLlng and 8ange of MoLlon
4 3 SeaLlng and oslLlonlng
4 4 AdapLlve LqulpmenL and uevlces
4 3 Soclal Skllls uevelopmenL
4 6 Sexual PealLh
4 LmploymenL
4 Pome ModlflcaLlons
4 9 Lelsure
4 10 Advocacy
O 9 Cngolng research
4 91 Lxonsklpplng
4 92 SLem cell replacemenL
4 93 uLrophln upregulaLlon
4 94 SupporLlve care drug developmenL
4 93 Cene Lherapy
4 96 Cllnlcal Lrlals
O 10 Counsellng
O 11 CrganlzaLlons speclflc Lo uMu
O 12 lamous sufferers of uMu
O 13 8eferences
O 14 LxLernal llnks
edit] Incidence/prevalence
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene, which is located on
the X chromosome. Due to this, DMD has an incidence oI 1 in 4,000
|2|
newborn males.
Mutations within the dystrophin gene can either be inherited or occur spontaneously during
germline transmission.
edit] ponym
DMD is named aIter the French neurologist Guillaume Benjamin Amand Duchenne (1806
1875), who Iirst described the disease in 1861
|3|
though it had already been described by the
Neapolitan physicians Giovanni Semmola in 1834 and Gaetano Conte in 1836
|4||5|
.
edit] Pathogenesis
Duchenne muscular dystrophy is caused by a mutation oI the dystrophin gene at locus Xp21.
Dystrophin is responsible Ior connecting the cytoskeleton oI each muscle Iiber to the underlying
basal lamina (extracellular matrix) through a protein complex containing many subunits. The
absence oI dystrophin permits excess calcium to penetrate the sarcolemma (cell membrane).
|6|

Alterations in these signalling pathways cause water to enter into the mitochondria which then
burst. In skeletal muscle dystrophy, mitochondrial dysIunction gives rise to an ampliIication oI
stress-induced cytosolic calcium signals and an ampliIication oI stress-induced reactive-oxygen
species (ROS) production. In a complex cascading process that involves several pathways and is
not clearly understood, increased oxidative stress within the cell damages the sarcolemma and
eventually results in the death oI the cell. Muscle Iibers undergo necrosis and are ultimately
replaced with adipose and connective tissue.
edit] Symptoms
The main symptom oI Duchenne muscular dystrophy, a progressive neuromuscular disorder, is
muscle weakness associated with muscle wasting with the voluntary muscles
|citation needed|
being
Iirst aIIected, especially aIIecting the muscles oI the hips, pelvic area, thighs, shoulders, and calI
muscles. Muscle weakness also occurs in the arms, neck, and other areas, but not as early as in
the lower halI oI the body. Calves are oIten enlarged. Symptoms usually appear beIore age 6 and
may appear as early as inIancy. The other physical symptoms are:
O Awkward manner of walklng sLepplng or runnlng (paLlenLs Lend Lo walk on Lhelr forefeeL
because of an lncreased calf Lonus Also Loe walklng ls a compensaLory adapLaLlon Lo knee
exLensor weakness)
O lrequenL falls
O laLlgue
O ulfflculLy wlLh moLor skllls (runnlng hopplng [umplng)
O lncreased Lumbar lordosls leadlng Lo shorLenlng of Lhe hlpflexor muscles 1hls has an effecL on
overall posLure and a manner of walklng sLepplng or runnlng
O Muscle conLracLures of achllles Lendon and hamsLrlngs lmpalr funcLlonallLy because Lhe muscle
flbers shorLen and flbrosls occurs ln connecLlve Llssue
O rogresslve dlfflculLy walklng
O Muscle flber deformlLles
O seudohyperLrophy (enlarglng) of Longue and calf muscles 1he muscle Llssue ls evenLually
replaced by faL and connecLlve Llssue hence Lhe Lerm pseudohyperLrophy
O Plgher rlsk of neurobehavloral dlsorders (eg AuPu) learnlng dlsorders (dyslexla) and non
progresslve weaknesses ln speclflc cognlLlve skllls (ln parLlcular shorLLerm verbal memory)
whlch are belleved Lo be Lhe resulL of absenL or dysfuncLlonal dysLrophln ln Lhe braln
O LvenLual loss of ablllLy Lo walk (usually by Lhe age of 12)
O SkeleLal deformlLles (lncludlng scollosls ln some cases)
edit] Signs and tests
Muscle wasting begins in the legs and pelvis, then progresses to the muscles oI the shoulders and
neck, Iollowed by loss oI arm muscles and respiratory muscles. CalI muscle enlargement
(pseudohypertrophy) is quite obvious. Cardiomyopathy(DCM) is common, but the development
oI congestive heart Iailure or arrhythmias (irregular heartbeats) is only occasional.
O A poslLlve Cowers slgn reflecLs Lhe more severe lmpalrmenL of Lhe lower exLremlLles muscles
1he chlld helps hlmself Lo geL up wlLh upper exLremlLles flrsL by rlslng Lo sLand on hls arms and
knees and Lhen walklng hls hands up hls legs Lo sLand uprlghL
O AffecLed chlldren usually Llre more easlly and have less overall sLrengLh Lhan Lhelr peers
O CreaLlne klnase (CkMM) levels ln Lhe bloodsLream are exLremely hlgh
O An elecLromyography (LMC) shows LhaL weakness ls caused by desLrucLlon of muscle Llssue
raLher Lhan by damage Lo nerves
O CeneLlc LesLlng can reveal geneLlc errors ln Lhe xp21 gene
O A muscle blopsy (lmmunohlsLochemlsLry or lmmunobloLLlng) or geneLlc LesL (blood LesL)
conflrms Lhe absence of dysLrophln alLhough lmprovemenLs ln geneLlc LesLlng ofLen make Lhls
unnecessary
edit] Diagnosis
[edit] DNA test
The muscle-speciIic isoIorm oI the dystrophin gene is composed oI 79 exons, and DNA testing
and analysis can usually identiIy the speciIic type oI mutation oI the exon or exons that are
aIIected. DNA testing conIirms the diagnosis in most cases.
|7|

[edit] Muscle biopsy
II DNA testing Iails to Iind the mutation, a muscle biopsy test may be perIormed. A small
sample oI muscle tissue is extracted (usually with a scalpel instead oI a needle) and a dye is
applied that reveals the presence oI dystrophin. Complete absence oI the protein indicates the
condition.
Over the past several years DNA tests have been developed that detect more oI the many
mutations that cause the condition, and muscle biopsy is not required as oIten to conIirm the
presence oI Duchenne's.
[edit] Prenatal tests
DMD is carried by an X-linked recessive gene. Males have only one X chromosome, so one
copy oI the mutated gene will cause DMD. Fathers cannot pass X-linked traits on to their sons,
so the mutation is transmitted by the mother.
|8|

II the mother is a carrier, and thereIore one oI her two X chromosomes has a DMD mutation,
there is a 50 chance that a Iemale child will inherit that mutation as one oI her two X
chromosomes, and be a carrier. There is a 50 chance that a male child will inherit that mutation
as his one X chromosome, and thereIore have DMD.
Prenatal tests can tell whether their unborn child has the most common mutations, and they may
choose to have an abortion. There are many mutations responsible Ior DMD, and some have not
been identiIied, so genetic testing only works when Iamily members with DMD have a mutation
that has been identiIied.
Chorion villus sampling (CVS) can be done at 1114 weeks, and has a 2 risk oI miscarriage.
Amniocentesis can be done aIter 15 weeks, and has a 0.5 risk oI miscarriage. Fetal blood
sampling can be done at about 18 weeks.
|citation needed|
Another option in the case oI unclear
genetic test results is Ietal muscle biopsy.
edit] Treatment
There is no current cure Ior DMD, although phase 1-2a trials with exon-skipping treatment Ior
certain mutations have halted decline and produced small clinical improvements in walking.
Treatment is generally aimed at controlling the onset oI symptoms to maximize the quality oI
liIe, and include the Iollowing:
O CorLlcosLerolds such as prednlsolone and deflazacorL lncrease energy and sLrengLh and defer
severlLy of some sympLoms
O 8andomlsed conLrol Lrlals have shown LhaL beLa2agonlsLs lncrease muscle sLrengLh buL do noL
modlfy dlsease progresslon lollowup Llme for mosL 8C1s on beLa2agonlsLs ls only around 12
monLhs and hence resulLs cannoL be exLrapolaLed beyond LhaL Llme frame
cltotloo oeeJeJ

O Mlld non[arrlng physlcal acLlvlLy such as swlmmlng ls encouraged lnacLlvlLy (such as bed resL)
can worsen Lhe muscle dlsease
O hyslcal Lherapy ls helpful Lo malnLaln muscle sLrengLh flexlblllLy and funcLlon
O CrLhopedlc appllances (such as braces and wheelchalrs) may lmprove moblllLy and Lhe ablllLy for
selfcare lormflLLlng removable leg braces LhaL hold Lhe ankle ln place durlng sleep can defer
Lhe onseL of conLracLures
O ApproprlaLe resplraLory supporL as Lhe dlsease progresses ls lmporLanL
Comprehensive multi-disciplinary care standards/guidelines Ior DMD have been developed by
the Centers Ior Disease Control and Prevention (CDC), and were published in two parts in The
Lancet Neurology in 2010. To download the two articles in PDF Iormat, go to the TREAT-NMD
website: http://www.treat-
nmd.eu/downloads/Iile/standardsoIcare/dmd/lancet/thediagnosisandmanagementoIdmdla
ncetcompletewitherratum.pdI
[edit] Prognosis
Duchenne muscular dystrophy eventually aIIects all voluntary muscles and involves the heart
and breathing muscles in later stages. The liIe expectancy typically ranges Irom the late teens to
the mid-20s.
|9|
Recent advancements in medicine are extending the lives oI those aIIlicted.
In rare cases, persons with DMD have been seen to survive into the Iorties or early IiIties, with
the use oI proper positioning in wheelchairs and beds, ventilator support (via tracheostomy or
mouthpiece), airway clearance, and heart medications, iI required.
|citation needed|
Early planning oI
the required supports Ior later-liIe care has shown greater longevity in people living with DMD.
[edit] Pbysical tberapy
Physical therapists are concerned with enabling children to reach their maximum physical
potential. Their aim is to:
O mlnlmlze Lhe developmenL of conLracLures and deformlLy by developlng a programme of
sLreLches and exerclses where approprlaLe
O anLlclpaLe and mlnlmlze oLher secondary compllcaLlons of a physlcal naLure
O monlLor resplraLory funcLlon and advlse on Lechnlques Lo asslsL wlLh breaLhlng exerclses and
meLhods of clearlng secreLlons
O Schedule weekly Lo monLhly sesslons aL a massage LheraplsL Lo allevlaLe paln presenL
[edit] Mecbanical ventilatoryJrespiration assistance
Modern "volume ventilators/respirators," which deliver an adjustable volume (amount) oI air to
the person with each breath, are valuable in the treatment oI people with muscular dystrophy
related respiratory problems. The ventilator may require an invasive endotracheal or tracheotomy
tube through which air is directly delivered, but, Ior some people non-invasive delivery through a
Iace mask or mouthpiece is suIIicient. Positive airway pressure machines, particularly bi-level
ones, are sometimes used in this latter way. The respiratory equipment may easily Iit on a
ventilator tray on the bottom or back oI a power wheelchair with an external battery Ior
portability.
Ventilator treatment may start in the mid to late teens when the respiratory muscles can begin to
collapse. II the vital capacity has dropped below 40 percent oI normal, a volume
ventilator/respirator may be used during sleeping hours, a time when the person is most likely to
be under ventilating ("hypoventilating"). Hypoventilation during sleep is determined by a
thorough history oI sleep disorder with an oximetry study and a capillary blood gas (See
Pulmonary Function Testing).
II the vital capacity continues to decline to less than 30 percent oI normal, a volume
ventilator/respirator may also be needed during the day Ior more assistance. The person
gradually will increase the amount oI time using the ventilator/respirator during the day as
needed.
However, there are also people with the disease in their 20's who have no need Ior a ventilator.
edit] Occupational and Physical Therapy
The goal oI occupational therapy is to obtain a clear understanding oI the individual, oI their
social circumstances, and oI their environment in order to develop a treatment plan that will
improve their quality oI liIe.
|10|
Individuals with DMD oIten experience diIIiculties in areas oI
selI-care, productivity, and leisure. This is related to the eIIects oI the disorder, such as decreased
mobility, decreased strength and postural stability, progressive deterioration oI upper-limb
Iunction, and contractures.
|10|
Occupational and physical therapists address an individual's
limitations using meaningIul occupations and by grading the activity, by using diIIerent
assessments and resources such as splinting, bracing, manual muscle testing (MMT), ROM,
postural intervention, and equipment prescription.
|11|

[edit] Splinting and Urtboses
Splints, also reIerred to as orthoses, are designed to maintain or improve ROM, prevent
deIormity, and improve Iunction. Splints help to support and keep limbs stretched, which delays
or prevents the onset oI contractures that commonly aIIect the knees, hips, Ieet, elbows, wrists,
and Iingers.
|11|
An ankle Ioot orthoses (AFO) can be used during sleep or during the day. The
purpose oI this is to keep the Ioot Irom pointing downward and sustain the stretch oI the achilles
tendon.
|11|
Maintaining the length oI the tendo-achilles, also reIerred to as the gastrocnemius-
soleus complex, which is extremely important Ior walking. Knee ankle Ioot orthoses (KAFO) are
also used Ior walking or Ior standing and can be used to prolong ambulation or help delay the
onset oI lower limb contractures.
|11|

[edit] Manual Muscle Testing and Range of Motion
MMT is used to evaluate muscular strength, whereas goniometry or ROM tests measure
movement around a joint. These tests indicate need Ior intervention such as passive and active
ROM, strengthening and splinting. Passive ROM combined with the use oI night splints can
signiIicantly improve tendo-achilles contractures.
|12|

[edit] Seating and Positioning
Proper seating is essential to prevent spinal curvatures. Severe scoliosis is common in DMD and
can interIere with sitting, sleeping, and breathing.
|13|
A wheelchair that is Iitted appropriately
accounts Ior Irame size, type oI seat, lumbar support, and cushioning to avoid pressure ulcers.
|10|

It should be equipped with other mechanical devices, such as tilt ability, in order to provide
comIort and to protect the skin. Power wheelchairs are indicated Ior most clients who can no
longer ambulate, as they do not have enough upper extremity strength to propel a manual
wheelchair independently.
|10|
DMD aIIects many people in their adolescence, thereIore, it is
crucial Ior occupational therapists to be conscious that signiIicant development may occur during
this time.
|13|
Without proper seating and postural support throughout development, deIormation
may occur, which could result in dysIunctional positioning. It is important Ior occupational
therapists to re-evaluate the Iit oI an individual`s wheelchair as oIten as every year during
adolescence .
|13|

[edit] Adaptive Equipment and Devices
There are many alternate mobility options, positioning aids, and other equipment that
occupational therapists may prescribe. These include walkers or quad-canes, which can be used
Ior individuals who are able ambulate to reduce the risk oI Ialling. In addition, transIer boards,
mechanical liIts, and speciIic transIerring education are important because Iractures have been
seen to occur during transIers as a result oI osteoporosis.
|14|
Handheld shower heads and bath
benches are indicated to enable individuals to manage their own selI-care needs as much as
possible.
|14|
Individuals who are able to bear weight and take a Iew steps may utilize commode
chairs, thus giving them the ability to toilet independently.
|14|
To complement an individualized
wheelchair, an occupational therapist may also consider prescribing a hospital bed, pressure-
relieving mattresses, and Ioam wedges Ior proper positioning to prevent pressure skin ulcers,
contractures, and deIormities.
|10|
Specialized trays, input devices and soItware may be prescribed
to Iacilitate computer use as well.
[edit] Social Skills Development
Along with physical diIIiculties, individuals with DMD may have social issues that an
occupational therapist can assist them in overcoming.
|14|
Group sessions or individualized
programs that Iocus on coping mechanisms Ior depression are examples oI what an occupational
therapist can Iacilitate.
|14|
SelI-esteem building Ior individuals oI all ages is an essential part oI
ensuring that a high quality oI liIe is achieved.
|14|
Occupational therapy intervention can play an
essential role in supporting the development oI social skills through group interactions and other
liIe experiences.
|14|
An occupational therapist can use a variety oI psychosocial Irameworks Ior
developing strategies and techniques Ior individuals to utilize, which will help them work
through various psychosocial issues they may be experiencing.
|10|

[edit] Sexual Healtb
Sexuality is a topic that many people Ieel uncomIortable discussing and thus may be overlooked
by health care proIessionals. An occupational therapist will educate individuals with DMD on
saIe and eIIective ways to experience their sexual liIe.
|10|
Such education can include various
Iorms oI sex as well as numerous positions that they would be able to perIorm.
|10|

[edit] Employment
Gaining and maintaining employment can be diIIicult Ior individuals with DMD. An
occupational therapist may collaborate with an individual, employer, and case manager to ensure
that the individual`s work environment is as enabling and accessible as possible.
|10|
By adapting
the physical work environment, the social environment, and the work requirements and
guidelines, an individual can maintain meaningIul employment as well as be as an asset to his or
her employer. This may not only impact the individual`s perceived selI-eIIicacy but also his or
her Iinancial well being.
|10|

[edit] Home Modifications
Maintaining independence is oIten a main Iocus oI occupational therapy interventions iI it is a
priority oI the client. Within the home, there are numerous obstacles that may prevent a client
Irom being as independent as possible. Home modiIications and adaptations are something that
an occupational therapist can assist with.
|10|
Such modiIications may include: railings Ior saIe
mobility and transIers, liIts, adapted kitchens that are accessible Ior wheelchairs, and bathroom
modiIications such as raised toilet seats or modiIied baths.
|10|
For example providing adaptive
equipment Ior playing computer and video games, supports Ior biking and adaptations Ior Iishing
rods.
[edit] Leisure
An occupational therapist can support individuals with DMD to Iind leisure activities that are
meaningIul Ior them to participate in; accommodations and adaptations can be made to enhance
participation.
|10|

[edit] Advocacy
In order to create a successIul therapeutic relationship it is important to coordinate with Iamily
members, Iriends, and other social resources to ensure that a person with DMD has both physical
and emotional support. An occupational therapist can act as an advocate Ior his or her client and
can educate those around him or her regarding inIormation about the illness, supports, resources,
and other concerns.
|10|
An occupational therapist can also provide his or her client with the tools
to learn how to advocate Ior him or herselI.
|10|

edit] Ongoing research

1hls arLlcle may conta|n or|g|na| research lease lmprove lL by verlfylng Lhe clalms made and
addlng references SLaLemenLs conslsLlng only of orlglnal research may be removed More deLalls
may be avallable on Lhe Lalk page %ctobet 2007)
Current research includes exon-skipping, stem cell replacement therapy, analog up-regulation,
gene replacement and supportive care to slow disease progression.
[edit] Exon-skipping
Antisense oligonucleotides, structural analogs oI DNA, are the basis oI a potential therapy Ior
patients aIIlicted with DMD. Two kinds oI antisense oligos, Morpholino oligos and 2'-O-methyl
phosphorothioate oligos, have been tested in early-phase clinical trials Ior DMD and have
restored some dystrophin expression in muscles oI DMD patients with a particular class oI
DMD-causing mutations. Further clinical trials are proceeding with these compounds.
Oligo-mediated exon skipping has resulted in clinical improvement in 12 patients in a Phase 1-2a
study. On a standard test, the 6-minute walk test, patients whose perIormance had been declining
instead improved, Irom 385 meters to 420 meters.
|15||16|
DMD may result Irom mRNA that
contains out-oI-Irame mutations (e.g. deletions, insertions or splice site mutations), resulting in
IrameshiIt or early termination so that in most muscle Iibers no Iunctional dystrophin is produced
(though some revertant muscle Iibers produce some dystrophin). In many cases an antisense
oligonucleotide can be used to trigger skipping oI an adjacent exon to restore the reading Irame
and production oI partially-Iunctional dystrophin.
Patients with Becker's muscular dystrophy, which is milder than DMD, have a Iorm oI
dystrophin which is Iunctional even though it is shorter than normal dystrophin.
|17|
In 1990
England et al. noticed that a patient with mild Becker muscular dystrophy was lacking 46 oI
his coding region Ior dystrophin.
|17|
This Iunctional, yet truncated, Iorm oI dystrophin gave rise
to the notion that shorter dystrophin can still be therapeutically beneIicial. Concurrently, Kole et
al. had modiIied splicing by targeting pre-mRNA with antisense oligonucleotides (AONs).
|18|

Kole demonstrated success using splice-targeted AONs to correct missplicing in cells removed
Irom beta-thalassemia patients
|19||20|
Wilton's group tested exon skipping Ior muscular
dystrophy.
|21||22|
SuccessIul preclinical research led to the current eIIorts to use splice-modiIying
oligos to change DMD dystrophin to a more Iunctional Iorm oI dystrophin, in eIIect converting
Duchenne MD into Becker MD.
Though AONs hold promise, one oI their major pitIalls is the need Ior periodic redelivery into
muscles. Systemic delivery on a recurring basis is being tested in humans
(http://clinicaltrials.gov/ct2/show/NCT00844597). To circumvent the requirement Ior periodic
oligo delivery, a long-term exon-skip therapy is being explored. This therapy consists oI
modiIying the U7 small nuclear RNA at the 5' end oI the non-translated RNA to target regions
within pre-mRNA. This has been shown to work in the DMD equivalent mouse, mdx.
|23|

[edit] Stem cell replacement
Though stem cells isolated Irom the muscle (satellite cells) have the ability to diIIerentiate into
myotubes when injected directly into the muscle oI animals, they lack the ability to spread
systemically throughout. To eIIectively deliver a therapeutic dose to an isolated muscle it would
require direct injections to that muscle every 2mm.
|24|
This problem was circumvented by using
another multipotent stem cell, termed pericytes, that are located within the blood vessels oI
skeletal muscle. These cells have the ability to be delivered systemically and uptaken by crossing
the vascular barrier. Once past the vasculature, pericytes have the ability to Iuse and Iorm
myotubes.
|25|
This means that they can be injected arterially, crossing through arterial walls into
muscle, where they can diIIerentiate into potentially Iunctional muscle. These Iindings show
potential Ior stem cell therapy oI DMD. The pericyte-derived cells would be extracted, grown in
culture, and then these cells would be injected into the blood stream where the possibility exists
that they might Iind their way into injured regions oI skeletal muscle.
[edit] Utropbin upregulation
Upregulation oI utrophin, whose gene is located on chromosome 6, can partially compensate Ior
the lack oI dystrophin in mice. Human testing is planned.
|citation needed|
.
[edit] Supportive care - drug development
Recent research shows Losartan, a currently available drug used Ior treating hypertension, to be
eIIective in halting the progress oI the disease in mice that were genetically engineered to have
Duchenne's.
|26|
Human trials are in planning.
Research Irom a group in France led by L. Segalat has identiIied a number oI drugs that are
currently licensed Ior other applications as halting or reducing dramatically the advance oI
muscle degeneration in a worm model oI DMD.
|27|
They are now using mouse models to conIirm
these Iindings, which so Iar are looking very promising, conIirming the eIIicacy oI these drugs.
However, work in mice seems to be moving slowly. The main classes oI drugs they identiIied
were SSRI (i.e. antidepressants such as Prozac) and muscle relaxants, such as those used by
athletes aIter heavy training. There is conIlicting evidence Irom animal models suggesting that
doing less exercise slows down the rate oI degeneration oI the muscle; thereIore there is a
possibility that both these drugs act somewhat as sedatives, although the reality seems to be that
the worms and mice are more active overall, as they have less muscle damage and so can remain
active Ior much longer.
More recently, a group at the Montreal Heart Institute and McGill University reported that a
mouse model oI Duchenne's muscular dystrophy demonstrated early metabolic alterations that
precede overt cardiomyopathy and may represent an early "subclinical" signature oI a deIective
nitric oxide (NO)/cGMP pathway. Accordingly, they used genetic and pharmacological
approaches to test the hypothesis that enhancing cGMP, downstream oI NO Iormation, improves
the contractile Iunction, energy metabolism, and sarcolemmal integrity. Treatment with
SildenaIil delayed the appearance oI symptoms in mouse hearts with Duchenne's and allowed to
withstand an acutely increased cardiac workload.
|28|

[edit] Cene tberapy
In 2007, a team oI researchers led by Jerry Mendell, M.D., at Nationwide Children's Hospital did
the world's Iirst clinical (viral-mediated) gene therapy trial Ior Duchenne MD.
|29|

ScientiIic research published on 15 April 2010 Irom the Universite Laval's Faculty oI Medicine
and the CHUQ Research Center indicates it is possible to repair the gene associated with causing
DMD through the use oI meganuclease enzymes though signiIicant work remains until it can be
tested in human patients.
|30|

Biostrophin is a delivery vector Ior gene therapy in the treatment oI Duchenne muscular
dystrophy and Becker muscular dystrophy.
|31|

[edit] Clinical trials
While PTC124 showed promising results in mice,
|32||33|
the Phase II trial was suspended when
participants did not show signiIicant increases in the six minute walk distance.
|34|

SaIety and eIIicacy studies oI antisense oligonucleotides Ior exon skipping in Duchenne
muscular dystrophy with Morpholino oligos
|35|
and with 2'-O-methyl phosphorothioate oligos
|36|

are in progress.
ACE-031 is in phase IIa. Patients with DMD are currently being enrolled to continue the clinical
trail that is being sponsored by Acceleron Pharma, Inc with the Iinancial help oI Shire who paid
$45 million upIront to enroll candidates. The estimated study completion date is set to be
February 2012.
|37||38|

Currently, this is the most promising successIul treatment Ior DMD and similar disorders.
edit] Counseling
Genetic counseling is advised Ior people with a Iamily history oI the disorder. Duchenne
muscular dystrophy can be detected with about 95 accuracy by genetic studies perIormed
during pregnancy.