Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy (DMD)(DMD)

Dr. Mohamed AbunadaDr. Mohamed AbunadaPediatric Neurology Pediatric Neurology

DepartmentDepartmentDr. Al rantisi specialized Dr. Al rantisi specialized

children Hospitalchildren Hospital

Muscular DystrophyMuscular Dystrophy First described in the 1830’s muscular First described in the 1830’s muscular

dystrophy is a group of more than 30 dystrophy is a group of more than 30 diseases that affect the skeletal diseases that affect the skeletal muscles muscles These muscles will experience progressive These muscles will experience progressive

weakening and eventually degeneration weakening and eventually degeneration Muscular dystrophy can affect the heart, Muscular dystrophy can affect the heart,

lungs, eyes, spine, brain, endocrine lungs, eyes, spine, brain, endocrine system, and gastrointestinal system as system, and gastrointestinal system as well as other organs. well as other organs.

Major ClassificationsMajor Classifications

The dystrophies are a group of genetic The dystrophies are a group of genetic myopathies. myopathies.

The usual cause is a defect in a structural proteinThe usual cause is a defect in a structural protein For most dystrophies, the abnormal gene and For most dystrophies, the abnormal gene and

gene product are established.gene product are established. There are eight major classifications of muscular There are eight major classifications of muscular

dystrophy. Each classification differs by the dystrophy. Each classification differs by the “extent and distribution of muscle weakness, age “extent and distribution of muscle weakness, age of onset, rate of progression, severity of of onset, rate of progression, severity of symptoms, and family history (including any symptoms, and family history (including any pattern of inheritance)” . pattern of inheritance)” .

ClassificationsClassifications

1. Duchenne MD*1. Duchenne MD* 2. Becker MD2. Becker MD 3. Facioscapulohumeral MD *3. Facioscapulohumeral MD * 4. Myotonic MD*4. Myotonic MD* 5. Emery-Dreifuss MD5. Emery-Dreifuss MD 6. Limb-girdle MD6. Limb-girdle MD 7. Congenital MD7. Congenital MD 8. Oculopharyngeal MD 8. Oculopharyngeal MD *most common forms*most common forms

Becker MDBecker MD

Cause is insufficient production of dystrophin, Cause is insufficient production of dystrophin, a protein that helps keep muscle cells intact. a protein that helps keep muscle cells intact.

Similar to Duchenne MD with a later onset and Similar to Duchenne MD with a later onset and slower progressionslower progression

The rate of progressive, symmetric muscle The rate of progressive, symmetric muscle atrophyatrophy and weakness varies greatly among and weakness varies greatly among affected individuals affected individuals

Emery-Dreifuss MDEmery-Dreifuss MD Cause is mutations in the genes that Cause is mutations in the genes that

produce emerin, lamin A or lamin C, produce emerin, lamin A or lamin C, proteins in the membrane that surrounds proteins in the membrane that surrounds the nucleus of each muscle cell.the nucleus of each muscle cell.

Onset is usually by 10 years of age.Onset is usually by 10 years of age. This disease causes slow but This disease causes slow but

progressive wasting of the upper arm progressive wasting of the upper arm and lower leg muscles and symmetric and lower leg muscles and symmetric weakness weakness

Congenital MD Congenital MD

Cause is genetic mutations affecting some of Cause is genetic mutations affecting some of the proteins necessary for muscles and the proteins necessary for muscles and sometimes for the eyes and or brain. (MEB sometimes for the eyes and or brain. (MEB Syndrome, Walker Warburg Syndrome)Syndrome, Walker Warburg Syndrome)

Present at birth or evident by age 2 Present at birth or evident by age 2 Varies with type; many are slowly progressive; Varies with type; many are slowly progressive;

some shorten life span some shorten life span The majority of patients are unable to sit or The majority of patients are unable to sit or

stand without support, and some affected stand without support, and some affected children may never learn to walk children may never learn to walk

Limb-Girdle Muscular DystrophiesLimb-Girdle Muscular Dystrophies

Autosomally determined face-sparing, Autosomally determined face-sparing, proximally predominant, progressive muscular proximally predominant, progressive muscular dystrophiesdystrophies 10% autosomal dominant(6 subtypes, LGMD1A-F)10% autosomal dominant(6 subtypes, LGMD1A-F) 90% autosomal recessive(11 subtypes, LGMD2A-K)90% autosomal recessive(11 subtypes, LGMD2A-K)

Age at onset varies greatly (usually 1Age at onset varies greatly (usually 1stst – 3 – 3rdrd decade)decade)

Defective proteins coded by mutant genes may Defective proteins coded by mutant genes may be detected by immunohistochemistry or be detected by immunohistochemistry or immunoblottingimmunoblotting

Limb-girdle dystrophiesLimb-girdle dystrophies

Causes:Causes: SarcoglycanopathiesSarcoglycanopathies Calpain deficiencyCalpain deficiency Caveolin deficiencyCaveolin deficiency Dysferlin deficiency etc.Dysferlin deficiency etc.

α, β, γ, δ sarcoglycansα, β, γ, δ sarcoglycans

SarcoglycanopathiesSarcoglycanopathies Clinical presentation:Clinical presentation:

Age of onset and severity is heterogeneous, usually Age of onset and severity is heterogeneous, usually starts between 2 and 20 yearsstarts between 2 and 20 years

Clinically often indistinguishable from Duchenne-Clinically often indistinguishable from Duchenne-dystrophydystrophy

No cardiac involvementNo cardiac involvement Diagnosis:Diagnosis:

Normal dystrophin immunostaining, abnormal Normal dystrophin immunostaining, abnormal immunostaining with sarcoglycansimmunostaining with sarcoglycans

Genetic examination, where availableGenetic examination, where available

Myotonic MD Myotonic MD

Cause is a repeated section of DNA on either Cause is a repeated section of DNA on either chromosome 19 or chromosome 3.chromosome 19 or chromosome 3.

Onset of the congenital form appears at birth. More Onset of the congenital form appears at birth. More common forms may begin in teen or adult years. common forms may begin in teen or adult years.

Affects the central nervous system and other body Affects the central nervous system and other body systems, including the heart, adrenal glands and systems, including the heart, adrenal glands and thyroid, eyes, and gastrointestinal tract thyroid, eyes, and gastrointestinal tract

Symptoms first seen in muscles in the hands and feetSymptoms first seen in muscles in the hands and feet Distinctive symptoms include muscle tensing, cramps, Distinctive symptoms include muscle tensing, cramps,

or inability to relax muscles.or inability to relax muscles.

Duchenne Muscular Dystrophy(DMD) Duchenne Muscular Dystrophy(DMD)

DMD affects mostly DMD affects mostly malesmales at a rate of at a rate of 1 in 3,500 1 in 3,500 birthsbirths..

There are over 200 types of mutations that can cause There are over 200 types of mutations that can cause any one of the forms of muscular dystrophy.any one of the forms of muscular dystrophy.

DMD is the DMD is the most severemost severe and and common typecommon type of of muscular dystrophy.muscular dystrophy.

DMD is characterized by the wasting away of muscles.DMD is characterized by the wasting away of muscles.Diagnosis in Diagnosis in boysboys usually occurs usually occurs between 16 months between 16 months

and 8 years.and 8 years.Parents are usually the first to notice problem.Parents are usually the first to notice problem.

Death from DMD usually occurs by age of 20.Death from DMD usually occurs by age of 20.

DMD Gene and DystrophinDMD Gene and DystrophinFunctionFunction

The DMD gene encodes for the protein The DMD gene encodes for the protein dystrophin, found in muscle cells and dystrophin, found in muscle cells and some neurons.some neurons.

Dystrophin provides strength to muscle cells by Dystrophin provides strength to muscle cells by linking the internal cytoskeleton to the surface linking the internal cytoskeleton to the surface membrane.membrane.

Without this structural support, the cell membrane Without this structural support, the cell membrane becomes permeable.becomes permeable.

Under normal wear and tear stem cells within the Under normal wear and tear stem cells within the muscle regenerate new muscle cells and repair muscle regenerate new muscle cells and repair the damage.the damage.

In DMD the damage to muscle cells is so extreme In DMD the damage to muscle cells is so extreme that the supply of stem cells are exhausted and that the supply of stem cells are exhausted and repair can no longer occur.repair can no longer occur.

Clinical FeaturesClinical FeaturesGenotype of DMDGenotype of DMD

Females carry the DMD Females carry the DMD gene on the X gene on the X chromosome.chromosome.

Females are carriers and have a Females are carriers and have a 50% chance of transmitting the 50% chance of transmitting the disease in each pregnancy.disease in each pregnancy.

Sons who inherit the mutation Sons who inherit the mutation will have the disease.will have the disease.

Daughters that inherit the Daughters that inherit the mutation will be carriers.mutation will be carriers.

The DMD gene is located on The DMD gene is located on the Xp 21 band of the X the Xp 21 band of the X chromosome.chromosome.

Genotype of DMDGenotype of DMD(Cont.)(Cont.)

During the translocation process, a mutation During the translocation process, a mutation occurs.occurs. Mutations leading to the Mutations leading to the absence of dystrophinabsence of dystrophin

Very Large Deletions (lead to absence of dystrophin)Very Large Deletions (lead to absence of dystrophin) Mutations causing Mutations causing reading errorsreading errors (causes a (causes a

degraded, low functioning DMD protein degraded, low functioning DMD protein molecule)molecule) DeletionDeletion DuplicationDuplication Point MutationsPoint Mutations

Clinical FeaturesClinical FeaturesPhenotype of DMDPhenotype of DMD

Delays in early childhood stages involving Delays in early childhood stages involving muscle use, in 42% of patients.muscle use, in 42% of patients.

Delays in standing aloneDelays in standing alone Delays in sitting without aidDelays in sitting without aid Delays in walking (12 to 24 months)Delays in walking (12 to 24 months)

Toe walking or flat footednees. Toe walking or flat footednees. Child has a hard time climbing.Child has a hard time climbing.

Learning difficulties in 5% of patients.Learning difficulties in 5% of patients. Speech problems in 3% of patients.Speech problems in 3% of patients. Leg and calf pain.Leg and calf pain. Mental development is impaired. IQ’s usually Mental development is impaired. IQ’s usually

below 75 points.below 75 points. Memory problemsMemory problems Carrying out daily functionsCarrying out daily functions

Clinical Features Clinical Features (Cont.)(Cont.)

Increase in bone fracturesIncrease in bone fractures due to the decrease due to the decrease in bone density.in bone density.

Wheelchair bound by 12Wheelchair bound by 12 years of age. years of age. Cardiomyopathy at 14 to 18 yearsCardiomyopathy at 14 to 18 years.. Few patients live beyond 30 years of age.Few patients live beyond 30 years of age.

RespiratoryRespiratory problems and problems and cardiomyopathy cardiomyopathy leading to leading to congestive heart failure are the usual cause of death.congestive heart failure are the usual cause of death.

Hypertrophicleg muscle

DMD

Enlarged calvesBMD Toe walking

BMD

Approach to Diagnosis of Childhood Muscular Approach to Diagnosis of Childhood Muscular DystrophyDystrophy

No DeletionDetected

Diagnosis of Dystrophinopathy (DM D or BM D)

Deletion NotInform ativefor Severity

Deletion Inform ativefor Severity.

Positive Fam ily History

DeletionDetected

DNA Analysisfor Dystrophin

G ene Abnorm ality

M ale

Abnorm alDystrophin

M erosin andAdhalin Analysis

Norm alDystrophin

M uscle Biopsy

Female

Elevated

M uscular DystrophyUnlike ly

Norm al

C K

M uscular W eakness

InvestigationsInvestigations Serum CPK LevelSerum CPK Level

management of DMD and BMD management of DMD and BMD

SYMPTOM MANAGEMENTSYMPTOM MANAGEMENT — In addition to — In addition to muscle weakness, muscle weakness, cardiaccardiac, , pulmonarypulmonary, and , and orthopedicorthopedic complications are frequently complications are frequently associated with DMD and BMD. associated with DMD and BMD.

The anticipation and early detection of organ The anticipation and early detection of organ involvement is important for optimal therapy.involvement is important for optimal therapy.

Furthermore, patients should be evaluated by Furthermore, patients should be evaluated by pulmonarypulmonary and and cardiac specialistscardiac specialists prior to any prior to any surgery . surgery .

American Thoracic Society guidelines American Thoracic Society guidelines recommend thatrecommend that

allall patients with DMD should receive the patients with DMD should receive the pneumococcal vaccinepneumococcal vaccine and an and an annual annual influenza vaccination.influenza vaccination. The pneumococcal The pneumococcal vaccine can provide immunity for 5 to 10 vaccine can provide immunity for 5 to 10 years. years.

Nocturnal mouth intermittent positive pressure Nocturnal mouth intermittent positive pressure Ventilation can be used to treat symptomatic Ventilation can be used to treat symptomatic nocturnal hypoventilation, and respiratory nocturnal hypoventilation, and respiratory assistance may be used during periods of assistance may be used during periods of respiratory infection respiratory infection

Cardiac diseaseCardiac disease angiotensin converting enzyme angiotensin converting enzyme (ACE)(ACE) inhibitors inhibitors

and and beta blockersbeta blockers, to treat asymptomatic left , to treat asymptomatic left ventricular dysfunction and overt heart failure.ventricular dysfunction and overt heart failure.

Echocardiography Echocardiography should be obtained around should be obtained around age 10 years in boys with DMD and BMD and age 10 years in boys with DMD and BMD and then repeated then repeated annuallyannually or or biannuallybiannually..

Cardiac evaluation of female carriers should Cardiac evaluation of female carriers should

begin after teenage years. begin after teenage years.

Orthopedic interventionsOrthopedic interventions

Therapeutic interventions in DMD/BMD are Therapeutic interventions in DMD/BMD are specifically aimed at specifically aimed at

1.maintaining function, 1.maintaining function, 2.preventing contractures. 2.preventing contractures. The mainstays of physical therapy are passive The mainstays of physical therapy are passive

stretching exercises to prevent contractures of the stretching exercises to prevent contractures of the iliotibial band, the Achilles tendons, and flexors of iliotibial band, the Achilles tendons, and flexors of the hip. the hip.

orthopedic interventionsorthopedic interventions Multiple additional interventions may be used based upon Multiple additional interventions may be used based upon

the patient's requirements and severity of disease: the patient's requirements and severity of disease: Lightweight plastic ankle-foot orthosesLightweight plastic ankle-foot orthoses should be applied if should be applied if

the foot remains in plantar flexion during sleep. the foot remains in plantar flexion during sleep. Standing and/or walking may be maintained by using Standing and/or walking may be maintained by using long-long-

leg braces. leg braces. SurgerySurgery may be performed to may be performed to release contractures of the hip release contractures of the hip

flexors, iliotibial bands, and Achilles tendons. flexors, iliotibial bands, and Achilles tendons. Standing and ambulation may prevent scoliosis. Standing and ambulation may prevent scoliosis. Spine surgerySpine surgery to stabilize or correct scoliosis may improve to stabilize or correct scoliosis may improve

patient comfort, particularly for those confined to a patient comfort, particularly for those confined to a wheelchair, and may benefit pulmonary function . wheelchair, and may benefit pulmonary function .

Orthopedic evaluationsOrthopedic evaluations should monitor for scoliosis and should monitor for scoliosis and other complications and surgical interventions should be other complications and surgical interventions should be utilized as needed. utilized as needed.

Chest and spine radiographyChest and spine radiography should be ordered on an as- should be ordered on an as-needed basis. needed basis.

NutritionNutrition Exposure to Exposure to sunshinesunshine and a and a balanced diet that balanced diet that

is rich in vitamin D and calciumis rich in vitamin D and calcium is important to is important to improve bone density and reduce the risk of improve bone density and reduce the risk of fractures. fractures.

Vitamin D supplementationVitamin D supplementation if the serum if the serum concentration of vitamin D is less than 20 concentration of vitamin D is less than 20 ng/mL is recommended. ng/mL is recommended.

Weight should be monitoredWeight should be monitored and controlled to and controlled to avoid obesity. It is recommended that patients avoid obesity. It is recommended that patients receive receive routine evaluation by a nutritionistroutine evaluation by a nutritionist. .

TREATMENTTREATMENT

CorticosteroidsCorticosteroids are the mainstay of treatment are the mainstay of treatment for for DMDDMD and are offered as treatment for and are offered as treatment for boys who are boys who are over the age of five years. over the age of five years.

PrednisonePrednisone —is beneficial in the treatment —is beneficial in the treatment of DMD and is associated with a significant of DMD and is associated with a significant increase in strengthincrease in strength, , muscle functionmuscle function, and , and pulmonary function.pulmonary function.

Little is known of the effect of prednisone in Little is known of the effect of prednisone in patients with BMD. patients with BMD.

Practice Parameter: Practice Parameter: Corticosteroid Treatment Of Corticosteroid Treatment Of

Duchenne Muscular DystrophyDuchenne Muscular Dystrophy

An Evidence-Based Report of the American Academy of An Evidence-Based Report of the American Academy of Neurology and the Child Neurology SocietyNeurology and the Child Neurology Society

Richard T. Moxley III, MD, Stephen Ashwal MD, Shree Richard T. Moxley III, MD, Stephen Ashwal MD, Shree Pandya, MS, PT, Anne Connolly, MD, Julaine Florence, Pandya, MS, PT, Anne Connolly, MD, Julaine Florence,

MHS, PT, Katherine Mathews, MD, Lisa Baumbach, MD, MHS, PT, Katherine Mathews, MD, Lisa Baumbach, MD, Craig McDonald, MD, Michael Sussman, MD, Craig McDonald, MD, Michael Sussman, MD,

Christine Wade, PhD, PTChristine Wade, PhD, PT

Published in Published in NeurologyNeurology 2005;64:13-20 2005;64:13-20

RecommendationsRecommendations PrednisonePrednisone has been demonstrated to have a has been demonstrated to have a

beneficial effect on muscle strength and function in beneficial effect on muscle strength and function in boys boys between 5 to 15 years of age between 5 to 15 years of age with DMD and should be with DMD and should be offered (at a dose of 0.75 mg/kg/d) as treatmentoffered (at a dose of 0.75 mg/kg/d) as treatment..

Maintaining Maintaining a dosage of 0.75 mg/kg/da dosage of 0.75 mg/kg/d is optimal; but, if is optimal; but, if side effects require a decrease in prednisone, tapering side effects require a decrease in prednisone, tapering to dosages as low as 0.3 mg/kg/d gives significant to dosages as low as 0.3 mg/kg/d gives significant improvement.improvement.

Benefits and side effects of corticosteroid therapy need Benefits and side effects of corticosteroid therapy need to be monitored. Timed function tests, pulmonary to be monitored. Timed function tests, pulmonary function tests, and age at loss of independent function tests, and age at loss of independent ambulation are useful to assess benefits. ambulation are useful to assess benefits.

An offer of treatment with corticosteroids should An offer of treatment with corticosteroids should include a balanced discussion of potential risks. include a balanced discussion of potential risks.

Potential side effects of corticosteroid therapy need to be assessed: •Weight gain

•Cushingoid appearance•Cataracts•Short stature •Acne•Excessive hair growth•Gastrointestinal symptoms•Behavioral changes

If excessive weight gain occurs (>20% over estimated normal weight for height over a 12 month period), based on available data, it is recommended that the dosage of prednisone be decreased (to 0.5 mg/kg/d with a further decrease after 3-4 months to 0.3 mg/kg/d if excessive weight gain continues).

Future Research Double blind, randomized, controlled studies are Double blind, randomized, controlled studies are

needed to compare daily treatment with prednisone to needed to compare daily treatment with prednisone to other treatment regimens, such as: other treatment regimens, such as: a)a) higher dose alternate day treatment (5 mg/kg every higher dose alternate day treatment (5 mg/kg every

other day) other day) b)b) intermittent treatment (0.75 mg/kg/d for 10 days – intermittent treatment (0.75 mg/kg/d for 10 days –

stop for 10 days – repeat cycle)stop for 10 days – repeat cycle)c)c) high dose pulses on weekends (5mg/kg on Friday high dose pulses on weekends (5mg/kg on Friday

and Saturday) and and Saturday) and d)d) deflazacort (0.9 mg/kg/d). deflazacort (0.9 mg/kg/d).

The goal of these studies is to establish more clearly The goal of these studies is to establish more clearly the optimal dose, optimal age to initiate treatment, and the optimal dose, optimal age to initiate treatment, and optimal dose schedule to improve function with the optimal dose schedule to improve function with the least possible side effects.least possible side effects.

NOVEL THERAPIESNOVEL THERAPIES

Gene therapyGene therapyExperimental gene therapies are currently under Experimental gene therapies are currently under

evaluation (whether by transplanted myoblast evaluation (whether by transplanted myoblast or direct genetic manipulation) .or direct genetic manipulation) .

CreatineCreatine Creatine monohydrate has been studied for its Creatine monohydrate has been studied for its

potential to increase muscle strength in NMD and potential to increase muscle strength in NMD and muscular dystrophies muscular dystrophies

Creatine treatment was associated with improved grip Creatine treatment was associated with improved grip strength of the dominant hand and increased fat free strength of the dominant hand and increased fat free mass compared with placebo. mass compared with placebo.

In light of the limited data and apparently modest In light of the limited data and apparently modest benefit attributed to creatine in the studies, benefit attributed to creatine in the studies, demonstration of clinically important improvement in demonstration of clinically important improvement in larger trials is needed before recommending this larger trials is needed before recommending this treatment for patients with DMD. treatment for patients with DMD.

Stem cell therapyStem cell therapy

The use of stem cells in the treatment of The use of stem cells in the treatment of DMD and BMD is under investigation but DMD and BMD is under investigation but remains experimental remains experimental

PROGNOSIS (DMD)PROGNOSIS (DMD) some improvement between three and six some improvement between three and six

years of age.years of age. followed by gradual deterioration, leading followed by gradual deterioration, leading

to wheelchair bounding by age of 12 yearsto wheelchair bounding by age of 12 years Most patients with DMD die in their late Most patients with DMD die in their late

teens or twenties from respiratory teens or twenties from respiratory insufficiency (most commonly) or insufficiency (most commonly) or arrhythmia secondary to cardiomyopathy. arrhythmia secondary to cardiomyopathy.

PROGNOSIS (BMD)PROGNOSIS (BMD) patients with BMD typically remain patients with BMD typically remain

ambulatory beyond the age of 16 years and ambulatory beyond the age of 16 years and into adult life.into adult life.

they survive beyond the age of 30 years. they survive beyond the age of 30 years. The most common cause of death is heart The most common cause of death is heart

failure from dilated cardiomyopathy, which failure from dilated cardiomyopathy, which also causes considerable morbidity in these also causes considerable morbidity in these patients despite their milder skeletal muscle patients despite their milder skeletal muscle involvement involvement

BibliographyBibliography Genes and disease.

Bethesda (MD): National Library of Medicine

Introduction to Genetic Analysis. 7th ed. Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. New York: ; c1999.

Human Molecular Genetics 2 2nd ed. Strachan, Tom and Read, Andrew P. New York and London: ; c1999

GeneReviews Editor-in-chief: Pagon, Roberta A. Associate editors: Cassidy, Suzanne B.; Bird, Thomas C.; Dinulos, Mary Beth; Feldman, Gerald L.; Smith, Richard J.H.; Dolan, Cynthia R. Technical editor: Baskin, Patricia K. Seattle (WA): University of Washington; 1993-2006

PubMedPubMed Houben F, Ramaekers FC, Snoeckx LH, Broers JL.Houben F, Ramaekers FC, Snoeckx LH, Broers JL.Role of nuclear lamina-cytoskeleton interactions in the maintenance of cellular strength.Role of nuclear lamina-cytoskeleton interactions in the maintenance of cellular strength.Biochim Biophys Acta.Biochim Biophys Acta. 2006 Sep 19; 2006 Sep 19; Maeda M, Nakao S, Miyazato H, Setoguchi M, Arima S, Higuchi I, Osame M, Taira A, Nomoto K, Toda H.Maeda M, Nakao S, Miyazato H, Setoguchi M, Arima S, Higuchi I, Osame M, Taira A, Nomoto K, Toda H.Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by endomyocardial biopsy.Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by endomyocardial biopsy.Am Heart J.Am Heart J. 1995 Apr; 1995 Apr; Kanagawa M, Toda T.Kanagawa M, Toda T.The genetic and molecular basis of muscular dystrophy: roles of cell-matrix linkage in the pathogenesis.The genetic and molecular basis of muscular dystrophy: roles of cell-matrix linkage in the pathogenesis.J Hum Genet.J Hum Genet. 2006 Sep 13; 2006 Sep 13; Beroud C, Tuffery-Giraud S, Matsuo M, Hamroun D, Humbertclaude V, Monnier N, Moizard MP, Voelckel MA, Calemard Beroud C, Tuffery-Giraud S, Matsuo M, Hamroun D, Humbertclaude V, Monnier N, Moizard MP, Voelckel MA, Calemard

LM, Boisseau P, Blayau M, Philippe C, Cossee M, Pages M, Rivier F, Danos O, Garcia L, Claustres MLM, Boisseau P, Blayau M, Philippe C, Cossee M, Pages M, Rivier F, Danos O, Garcia L, Claustres MMultiexon skipping leading to an artificial DMD protein lacking amino acids from exon 45 through 55 could rescue up to 63% of Multiexon skipping leading to an artificial DMD protein lacking amino acids from exon 45 through 55 could rescue up to 63% of

patients with Duchenne muscular dystrophy.patients with Duchenne muscular dystrophy.Hum Mutat.Hum Mutat. 2006 Oct 13; 2006 Oct 13; Ervasti JM.Ervasti JM.Dystrophin, its interactions with other proteins, and implications for muscular dystrophy.Dystrophin, its interactions with other proteins, and implications for muscular dystrophy.Biochim Biophys Acta. Biochim Biophys Acta. 2006 Jun 7;2006 Jun 7;