Muscular Dystrophy (MD) Therapeutics

GlobalData, the industry analysis specialist, has released its new report, "Muscular
Dystrophy (MD) Therapeutics - Pipeline Assessment and Market Forecasts to 2018".
The report is an essential source of information and analysis on the global MD
therapeutics market. The report identifies the key trends shaping and driving the
global MD therapeutics market. The report also provides insights on the prevalent
competitive landscape and the emerging players expected to significantly alter the
market positioning of the current market leaders. Most importantly, the report
provides valuable insights on the pipeline products within the global MD therapeutics
sector. This report is built using data and information sourced from proprietary
databases, primary and secondary research and in-house analysis by GlobalData's
team of industry experts.
GlobalData estimates that the global Muscular Dystrophy (MD) therapeutics market
to grow at a Compound Annual Growth Rate (CAGR) of 22.8%, from $33m in 2010 to
$170.9m in 2018. The market will show steady growth till 2010 and a steep increase
in the market valuations will be seen after 2014. This is primarily attributed to the
expected launch of two molecules GSK2402968 in 2014 and Catena/Sovrima
(idebenone)

in

2015

for

the

DuchenneMuscular

Dystrophy/Becker

Muscular

Dystrophy (DMD/BMD). The future market is set to witness significant high value
growth mainly due to the high cost of therapy of the pipeline molecules. The other
factors that will contribute to the growth of the market are high diagnosis and
treatment rates and increasing disease awareness. Absence of approved drugs and
the high use of off-label generic drugs, such as prednisolone, deflazacort, mexiletine,
naproxen and others will act as a barrier to the MD therapeutics market.
1

his is a consecutive study on 28 patients who have been diagnosed as having

congenital muscular dystrophy at Jordan University Hospital in the period from
January 1990 to February 1997. Of 75 patients diagnosed as having muscle disease,
55 (73.3%) had muscular dystrophy. Of 55 muscular dystrophy patients, 28 (50.9%)
had congenital muscular dystrophy, 11 (20%) had Duchenne muscular dystrophy, 9
(16.4%) had Becker muscular dystrophy, 9 (16.4%) had Becker muscular dystrophy,
4 (7.3%) had myotonic dystrophy, 2 (3.6%) had limb-girdle dystrophy, and 1 (1.8%)
patient had facioscapulohumeral dystrophy. Age of onset of symptoms of congenital
muscular dystrophy (hypotonia and weakness) was documented antenatally or in
the first few months in the majority (92.9%) of patients. Parental consanguinity was
documented in 21 (75%) of congenital muscular dystrophy cases, and family history
of possible similar cases in 15 (53.6%). Congenital muscular dystrophy patients with
normal cognitive milestones (n = 16; 57.1%) were slightly more common than
patients with cognitive delay. In contrast to previous reports, congenital muscular
dystrophy is probably more common in communities with high rates of parental
consanguinity than other dystrophies. Our study adds significant support to the most
recent literature on this finding. (J Child Neurol 1998; 13:383386).

Muscle diseases are common causes of lower motor neuron unit disorders.1
Muscular dystrophies are the most common muscle disease in children.2 Congenital
muscular dystrophy is a heterogeneous uncommon type of muscular dystrophy
when compared to the most frequently reported form of muscular dystrophy, the
Duchenne muscular dystrophy, which has an incidence of 1 in 3000 to 1 in 8000
male births.2-3 All congenital muscular dystrophy patients have autosomal recessive
inheritance, except for few reports of possible autosomal dominant inheritance and
2

sporadic cases.3 The aim of the present study was to evaluate the frequency and
clinical patterns of congenital muscular dystrophy in Jordanian children presenting
with muscle disease.

PATIENTS AND METHODS

This was a consecutive study, that included all children who had been diagnosed as
having muscular dystrophy with onset of their symptoms antenatally or in early
infancy. All children were evaluated by the first author in the pediatric neurology
service at Jordan University Hospital in the period between January 1990 and
February 1997. After clinical evaluation, nerve conduction study, electromyography,
serum creatine kinase enzyme study, and muscle biopsy were done on all of them.

Hematoxylin and eosin stain was done on all muscle biopsies (Figure 1). Mason
trichrome and periodic acid-Schiff stains were occasionally done for further
delineation of the abnormalities. No immunohistochemistry was done on any of our
patients because of lack of expertise and technical limitations in our lab. Brain
computed tomographic (CT) scans were requested for all cogitively delayed patients;
however, some patients refused the procedure because of financial reasons or they
were not convinced of the benefits from the procedure. Brain CT scans were done on
a few non-cognitively delayed patients to use as a control. Inclusion criteria were
weakness and hypotonia documented by history from the mother or from physician
notations antenatally or in early infancy. Each patient had serum creatine kinase
3

evaluation

done

within

years

from

onset

of

symptoms,

myopathic

electromyography, normal nerve conduction study, and muscle biopsy disclosing

dystrophic changes.6 Patients were divided into two major groups. Group A patients
had normal cognitive developmental milestones and group B had cognitive
developmental delay. Patients were considered cognitively delayed if they had delay
in language milestones in the absence of hearing impairment, or problem-solving
delay for age, or both.7-' Group A patients were further divided into three subgroups:
group Al had progressive course and high serum creatine kinase level, group A2 had
mild clin ical course with normal serum creatine kinase level, and group A3 had
mixed features.

RESULTS

Of 75 patients diagnosed to have muscle diseases, 55 (73.3%) patients had

muscular dystrophy. Of the 55 muscular dystrophy patients, 28 (50.9%) had
congenital muscular dystrophy, 11 (20%) had Duchenne muscular dystrophy, 9
(16.4%) had Becker muscular dystrophy, 4 (7.3%) had myotonic dystrophy, 2 (3.6%)
had limb-girdle muscular dystrophy, and 1 (1.8%) patient had facioscapulohumeral
dystrophy9 (Table 1). Age of onset of patients with symptoms of congenital muscular
dystrophy was documented antenatally in 2 (7.1%) patients, neonatal period in 10
(33.7%) patients, at 1-3 months in 14 (50%) patients, and at 4-9 months in 2 (7.1%)
patients. There were 16 females and 12 males. Serum creatine kinase levels did not
correlate with the different groups. The serum creatine kinase range in group Al was
279-7730 U/L with a mean of 2324 U/L and the serum creatine kinase range in group

B was 133-6405 U/L with a mean of 2123 U/L (normal value up to 110 U/L). Children
with progressive clinical course (mainly group Al) and children older than 3 years of
age at the time of the biopsy tended to have greater degree of muscle pathology in
the form of excessive fibrosis and adipose tissue replacing muscle fibers.

Group A patients were the majority (n = 16, 57.1%). Seven patients belonged to
group Al, another eight patients belonged to group A2, and one patient belonged to
group A3 (normal mental development, progressive weakness, and normal serum
creatine kinase level). Brain CT scans were done on four patients of group A, which
showed normal results. Group B included 12 (42.9%) patients with six of them
having normal serum creatine kinase levels. Seven patients of group B had brain CT
scans, four of them were abnormal. The first two patients had mild diffuse brain
atrophy, one of them had a high serum creatine kinase level. The third patient had
cobblestone lissencephaly, DandyWalker cyst, dilated ventricles, and occipital
encephalocele. He had also a high serum creatine kinase level, retinal dysplasia,
microophthalmia, and cataracts, suggesting Walker-Warburg syndrome (Figure 2).
The fourth patient had periventricular cortical white-matter abnormalities with
sparing of corpus callosum, internal capsule, and brain stem.10 He also had
microcephaly, seizures, optic atrophy, and high serum creatine kinase level.
Consanguinity was documented in 21 (75%) patients. First cousin and second cousin
marriages were encountered in 10 patients of group A and eight patients of group B.
Distant relation marriages were encountered in two patients of group A and one
patient of group B. Family history of possible similar cases with autosomal recessive
inheritance was documented in 15 (53.6%) patients (Table 2). No particular

correlation was noted between frequency of consanguinity and family history and
specific congenital muscular dystrophy groups.

DISCUSSION

Our study has shown that the most common muscle disease in Jordan is most
probably congenital muscular dystrophy, accounting for about one third of all muscle
diseases and about one half of all muscular dystrophies. This is in contrast to what
has been reported in the literature.1-3,11-13 The high rate (75%) of parental
consanguinity and the family history of possible similar cases (53.6%) among
congenital muscular dystrophy patients may partially explain such a finding, despite
the high incidence (50%) of parental consanguinity in our community.14 The role of
parental consanguinity in Arab populations in increasing the incidence of autosomal
recessive forms of neuromuscular disorders has been recently emphasized.15
Donner et al reported 15 cases of congenital muscular dystrophy from Finland
accounting for 9% of neuromuscular cases and he suggested that congenital
muscular dystrophy may be more common in Finland than elsewhere.16

View Image - Figure 1 Figure 2

View Image - Table 1.
Onset of symptoms (weakness and hypotonia) of congenital muscular dystrophy are
reported antenatally, at birth, or in the first few months.2,11,7 In our study,
symptoms were documented before age 3 months in 92.9% of cases. The
6

classification of congenital muscular dystrophy has long been a source of

uncertainty.2,3,17,18 Pa parano et ala proposed the most recent congenital
muscular dystrophy classification which included:

Classic congenital muscular dystrophy with merosin deficiency. These patients have
normal mental development, severe progressive symptoms and high serum creatine
kinase levels. Group Al patients in present study, fulfill the clinical diagnostic criteria
of this entity.

Classic congenital muscular dystrophy with normal merosin. Patients have normal
mental development, mild weakness and hypotonia, and usually normal serum
creatine kinase levels. Group A2 patients fulfill clinical diagnostic criteria of this
entity.

Congenital muscular dystrophy with mental retardation. Eleven of 12 patients of

group B probably correspond to this entity. One of these patients had brain CT with
whitematter changes similar to Saudi cases reported by Cook et al.10

Cobblestone lissencephaly syndrome such as Fukuyama congenital muscular

dystrophy, muscle-eye-brain disease and Walker-Warburg syndrome. The twelfth
patient of group B fulfilled the diagnostic criteria of Walker Warburg syndrome, which
has world wide distribution, in contrast to Fukuyama congenital muscular dystrophy

which occurs mainly in Japan and muscle-eye-brain disease which has been reported
primarily from Finland.13,17,19

Congenital muscular dystrophy with occipital pachygyria and atypical congenital

muscular dystrophy syndrome. None of our patients belong to these two entities.
One patient (group A3) probably belongs to the first entity in the Parano et al
classification (classic congenital muscular dystrophy with merosin deficiency) ie,
group Al in our study.3 The normal serum creatine kinase level in this patient is most
likely due to the severe muscle atrophy he had.

To conclude, congenital muscular dystrophy is a common muscular dystrophy in

Jordan. It is probably more common in communities with high rates of parental
consanguinity than other dystrophies. Our study adds significant support to the
scant literature on this finding, considering the relatively large number of our
patients compared to other studies. Immunohistochemical studies are definitely
helpful in defining accurately the various congenital muscular dystrophy entities.

Advocates in Muscular Dystrophy Community Press Congress for Fast Action on

Muscle Disease Research and Treatment

TUCSON, Ariz., Feb. 14, 2013 /PRNewswire-USNewswire/ -- The Muscular Dystrophy

Association, Parent Project Muscular Dystrophy and the Foundation to Eradicate

Duchenne today called on the U.S. Senate and the U.S. House of Representatives to
reauthorize the MD CARE Act of 2001, and to continue federal support for the
accelerated pace of research and treatment development for muscular dystrophy.
The nonprofits also are urging the public to contact their U.S. Senators and ask them
to vote for reauthorization of The Paul D. Wellstone Muscular Dystrophy Community
Assistance, Research and Education (MD CARE) Amendments of 2013. The Senate
introduced the bill last night (S. 315), and the House introduced the bill (H.R. 594)
Feb. 8.

Since 2001, federal funding and coordination of muscular dystrophy research has
dramatically enhanced discovery and development of potential treatments for the
muscular dystrophies, including: Duchenne and Becker muscular dystrophies
(DMD/BMD, or also known as DBMD); congenital muscular dystrophy (CMD);
facioscapulohumeral muscular dystrophy (FSHD); limb-girdle muscular dystrophy
(LGMD); and myotonic muscular dystrophy (MMD).

"Progress in muscle disease research since the MD CARE Act was passed has been
extraordinary," said MDA President and Chief Executive Officer Steven M. Derks.
"Sixty-seven clinical trials for drugs or therapies have been conducted since 2001,
with 37 clinical trials currently under way. Additionally, new clinical care guidelines
will be valuable tools to improve standards of care for those living with muscle
diseases. We are counting on the unparalleled strength of our nationwide muscular
dystrophy community to ensure that Congress understands the importance of this

reauthorization. We must build on the success of the MD CARE Act and deliver
effective treatments to those affected."

Senator Roger Wicker of Mississippi, author of the MD CARE Act of 2001, and Senator
Amy Klobuchar of Minnesota, sponsor of the 2008 reauthorization, are lead Senate
sponsors of the bill. In the House, Eliot Engel of New York and Dr. Michael Burgess of
Texas are leading the effort for reauthorization of the MD CARE Act as they did in
2008.

"In 2001, as we celebrated the signing of the MD CARE Act, we could not imagine its
impact," said Parent Project Muscular Dystrophy President and CEO Pat Furlong.
"Over the years, we have seen scientific breakthroughs across the muscular
dystrophies, which have led to the expansion and intensification of muscular
dystrophy research, including the leveraging of significant non-federal sources of
funding. Today, people with muscular dystrophy are living longer, more clinical trials
are in progress, and the hope of treatments is palpable within our community."

As a result of the accelerated pace of discovery and development of therapeutic

treatments, more young people with muscle disease are living longer and making
the transition into adulthood. This year's Amendment addresses that progress by
requiring studies to develop optimal clinical care interventions for young adults with
Duchenne and Becker muscular dystrophies (DMD/BMD).

"We are extremely grateful to members of Congress that have recognized the vital
importance of this legislation to advance Duchenne muscular dystrophy research
and produce real therapeutic approaches that are extending the lives of young men
living with the devastating impact of Duchenne muscular dystrophy every day," said
Joel Wood, president of the Foundation to Eradicate Duchenne. "This legislation and
the research and therapeutics it produces are bringing us closer to our goal of
finding a cure for this generation of Duchenne men."

The

proposed

legislation

also

mandates

studies

to

demonstrate

the

cost

effectiveness of providing independent living resources and support services for

young adults with all forms of muscular dystrophy.

"When I was first diagnosed with Becker muscular dystrophy 36 years ago, I'm not
sure that anyone would have envisioned I would be a 44-year-old man with a passion
for the Mets, Bruce Springsteen and serving as the University Dean for Student
Affairs at City University of New York," said Chris Rosa, Ph.D. "I've had to overcome
many obstacles along the way, and all too often the resources I needed to overcome
those obstacles did not exist. It's very encouraging to see this included in the
Amendment so that we can create smarter policies and clear away some of the
hurdles."

The 2013 MD CARE Amendment also:

directs the Muscular Dystrophy Coordinating Committee to consider a plan to

expedite approval of emerging therapies and personalized medicines with the
potential to treat people with muscular dystrophy;

expands areas of research focus within the NIH-funded Paul D. Wellstone Muscular
Dystrophy Centers of Excellence to include heart and lung function;

directs the CDC to develop and disseminate care considerations for adults with
Duchenne and Becker muscular dystrophies (DMD/BMD, or DBMD); and

directs the CDC to develop and disseminate acute care considerations for adults with
all muscular dystrophies.

MDA, PPMD and FED were instrumental in passage of the original act in 2001.

About Parent Project Muscular DystrophyDuchenne is a fatal genetic disorder that

slowly robs young men of their muscle strength. Parent Project Muscular Dystrophy
(PPMD) is the largest most comprehensive nonprofit organization in the United
States focused on finding a cure for Duchenne muscular dystrophy -- our mission is
to end Duchenne.

We invest deeply in treatments for this generation of young men affected by

Duchenne and in research that will benefit future generations. We advocate in
Washington, D.C., and have secured hundreds of millions of dollars in funding. We
demand optimal care, and we strengthen, unite and educate the global Duchenne
community.

Everything we do -- and everything we have done since our founding in 1994 -- helps
boys with Duchenne live longer, stronger lives. We will not rest until every young
man has a treatment to end Duchenne. Go to ParentProjectMD.org for more
information, or to learn how you can support our efforts and help families affected
by Duchenne.

About the Foundation to Eradicate DuchenneThe Foundation to Eradicate Duchenne

is a 501c(3) organization established in 2002 with the goal of finding treatments and
an ultimate cure for Duchenne muscular dystrophy, the world's leading lethal
childhood genetic disease.

The Foundation to Eradicate Duchenne was established by Dana and Joel Wood of
Alexandria, Va. Their son James Wood, now 15, was diagnosed in May 2000 with
Duchenne muscular dystrophy. The Woods are both lobbyists in Washington, D.C.,
and have devoted much of their time and energies to this cause, working with others
to attain millions of dollars in federal earmarks for Duchenne muscular dystrophy
research and a significant increase in the attention devoted to DMD at the National
5

Institutes of Health. Additionally, through the FED and other fundraising efforts, they
have raised approximately $10 million in private donations since James was
diagnosed.

About MDAMDA is the nonprofit health agency dedicated to finding treatments and
cures for muscular dystrophy, ALS and related diseases by funding worldwide
research. The Association also provides comprehensive health care and support
services, advocacy and education.

In addition to funding more than 250 research projects worldwide, MDA maintains a
national network of 200 medical clinics; facilitates hundreds of support groups for
families affected by neuromuscular diseases; and provides local summer camp
opportunities for thousands of youngsters living with progressive muscle diseases.

Contenido
Muscular Dystrophy (MD) Therapeutics........................................................................i
PATIENTS AND METHODS............................................................................................. ii
RESULTS.................................................................................................................. iii
DISCUSSION............................................................................................................ iv
Advocates in Muscular Dystrophy Community Press Congress for Fast Action on
Muscle Disease Research and Treatment....................................................................v
Foto............................................................................................................................. 5