Losartan

[varghakata]

Dear David.
Thanks quick replay.
My son runing ,run,play,play sport also.
I think is good for His heart.
But what about steroid also help His heart ?
With steroid He need the same dosis or less ?
Regards
W

[varghakata]

Dear David.
Thanks quick replay.
My son runp,play sport also.
Losartan think is good for His heart.
But what about steroid also help His heart ?
With steroid He need the same dosis or less ?
Regards

[ofelia]

David,

I am certain that they cannot finalize the all the exon skipping trials in 5 years. Some of the groups you mentioned did not even start any trials in humans. Only Prosensa and MDEX/AVI started the trails and only the proof of concept. So I have no doubt that the other groups cannot finish in 5 years since they don't even have the start date set-up. My question was about exon 51 skipping, which is the first they are working on (Prosensa and AVI). From what I read the plan is to have that competed 5-6 years from now IF everything works as well as they hope.

[David Feder]

Ofelia: I think that they will complete the study of exon51 to start others studies.

[David Feder]

Angiotensin II Receptor Blockade Administered After Injury Improves Muscle Regeneration and Decreases Fibrosis in Normal Skeletal Muscle
Hany S. Bedair, MD1, Tharun Karthikeyan, MD1, Andres Quintero, MD1, Yong Li, MD, PhD2, Johnny Huard, PhD2*

1 University of Pittsburgh Medical Center
2 University of Pittsburgh Medical Center and Stem Cell Research Center, Children's Hospital of Pittsburgh

* To whom correspondence should be addressed. E-mail: [e-mail].


Abstract

Background: Several therapeutic agents have been shown to inhibit fibrosis and improve regeneration after injury in skeletal muscle by antagonizing transforming growth factor-{beta}1. Angiotensin receptor blockers have been shown to have a similar effect on transforming growth factor-{beta}1 in a variety of tissues.

Hypothesis: Systemic treatment of animals after injury of skeletal muscle with an angiotensin receptor blocker may decrease fibrosis and improve regeneration, mainly through transforming growth factor-{beta}1 blockade, and can be used to improve skeletal muscle healing after injury.

Study Design: Controlled laboratory study.

Methods: Forty mice underwent bilateral partial gastrocnemius lacerations. Mice were assigned randomly to a control group (tap water), a low-dose angiotensin receptor blocker group (losartan, 0.05 mg/mL), or a high-dose angiotensin receptor blocker group (0.5 mg/mL). The medication was dissolved in tap water and administered enterally. Mice were sacrificed 3 or 5 weeks after injury, and the lacerated muscles were examined histologically for muscle regeneration and fibrosis.

Results: Compared with control mice at 3 and 5 weeks, angiotensin receptor blocker–treated mice exhibited a histologic dose-dependent improvement in muscle regeneration and a measurable reduction in fibrous tissue formation within the area of injury.

Conclusion: By modulating the response to local and systemic angiotensin II, angiotensin receptor blocker therapy significantly reduced fibrosis and led to an increase in the number of regenerating myofibers in acutely injured skeletal muscle. The clinical implications for this application of angiotensin receptor blockers are potentially far-reaching and include not only sports- and military-related injuries, but also diseases such as the muscular dystrophies and trauma- and surgery-related injury.

Clinical Relevance: Angiotensin receptor blockers may provide a safe, clinically available treatment for improving healing after skeletal muscle injury.


ajs.sagepub.com/cgi/content/abstract/0363546508315470v1?maxtoshow=&HITS=&hits=&RESULTFORMAT=1&andorexacttitle=and&fulltext=muscular+dystrophy&andorexactfulltext=and&searchid=1&FIRSTINDEX=10&sortspec=relevance&fdate=6/1/2008&resourcetype=HWCIT

[varghakata]

Hi David.
We done blood taste yestarday the CK was high 37960.
6 month ago it was about 10 000, You advice to increase losartan from 12.5 mg to 25 mg.wich I done.
We give Him beside losartan idebenone,Juven.Curcoma,carnitin,Q10,Vitamins.
Please mail Me what I can do more ?
Its very disquieting Me.....please.

[David Feder]

CK is not a good criterion to study the effect of treatment.
The most important is the results on muscle strenght, respiratory and cardiac function, and others.
CK is important to diagnosis. Only for diagnosis.
David

[lia]

hi david,
thanku for all yr efforts, yr website have been so helpful..
i just want to ask you about the learning abilities of MD boys.. are they any different? and if they are, how did the disease affet them in this aspect? i mean the disease is only supposed to affect their muscles, how come it affects their mental abilities?
thanku again
please reply

[David Feder]

Hi Lia: thank you! I think that membrane of neurons don't have dystrophin too. There are some controversy about symptoms of central nervous system in DMD. I found this article:


Original Articles

Specific cognitive deficits are common in children with Duchenne muscular dystrophy

--------------------------------------------------------------------------------
Rikard K Wicksell a1 c1, Margareta Kihlgren a2, Lennart Melin a1 and Orvar Eeg-Olofsson a3
a1 Department of Psychology, Uppsala University, Uppsala, Sweden.
a2 University Children's Hospital, Uppsala, Sweden.
a3 Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.



Abstract

A neuropsychological assessment was conducted to study cognition, with emphasis on memory, information processing/learning ability, and executive functions in boys with Duchenne muscular dystrophy (DMD). A group of 20 boys with DMD, aged 7 to 14 years (mean age 9 years 5 months, SD 2 years 2 months), was contrasted with 17 normally developing age-matched comparison individuals, using specific neuropsychological tests (Block Span, Digit Span, Story Recall, Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Spatial Learning Test, Verbal Fluency, Trail Making Test, Tower of London, Memory for Faces, and Raven's Coloured Progressive Matrices). The DMD group performed significantly worse on all aspects of memory, learning, and executive functions. There was no significant difference in general intellectual ability between the two groups. Analyses of group differences indicate that problems in short-term memory are the most apparent, suggesting specific cognitive deficits. The differences between the groups were similar for both verbal–auditory and visuospatial tests, thus contradicting the idea that cognitive deficits are related to type of stimulus presented. It is concluded from this study that short-term memory deficits might play a critical role in the cognitive impairment and intellectual development seen in those with DMD.

[Lia]

Dear David,
Thank you so much for your efforts.
I have understood from the article that short-term memory deficits might play a critical role in the cognitive impairment and intellectual development seen in DMD boys, but absolutely on the contrary my nephew has a great memory. He keeps on remembering old incidents, he almost remember everything. The only problem is that in school teachers complain that he refuses to learn, I mean he just drops the pencil and refuses to write, draw, or colour. The boy is only 6 years 3 months old. When he is asked to write or recite, he complains that he is tired. His parents are complaining too of the same problem, that he is never in the mood to learn. And if his mother worked hard on teaching him something, he is slower in memorizing the song or poem than his younger relatives and his friends at school. I mean its weird how he has this great memory that he can call back every detail, yet he cant learn things as fast as others his age and even younger. What do you think is the problem?
And does it mean he is Duchenne if he has these problems?
What’s the best clinical way to find out what type of muscular dystrophy does the boy has?
Thank you again

[David Feder]

Social Behavior Problems in Boys with Duchenne
Muscular Dystrophy
VERONICA J. HINTON, PH.D.
Gertrude H. Sergievsky Center and Department of Neurology, College of Physicians and Surgeons,
Columbia University, New York
NANCY E. NEREO, PH.D.
Department of Rehabilitation, Hospital for Special Surgery, New York
ROBERT J. FEE, B.A.
Gertrude H. Sergievsky Center, Columbia University, New York
SHANA E. CYRULNIK, B.A.
Gertrude H. Sergievsky Center, Columbia University and The Graduate Center of the City University of New York,
New York, New York
ABSTRACT. Duchenne muscular dystrophy (DMD) is a chronic, progressive pediatric disease that affects
both muscle and brain. The objectives of the study were to examine parent reported behavior in children with
DMD, investigate the influence of chronic illness, intellectual ability and etiology on behavior, and determine
whether a specific behavioral profile is associated with DMD. Parental ratings of boys with DMD (n = 181) on
the Child Behavior Checklist behavior scales were examined and compared to reported findings of children
with other chronic illnesses, unaffected siblings of boys with DMD (n = 86), and children with cerebral palsy
(CP) (n = 42). Increased ratings of general behavior problems were reported, and neither physical progression
nor intellectual level contributed to behavioral ratings. Among the children with DMD, the Social
Problem behavior scale had the greatest number of ‘‘clinically significant’’ ratings (34%). Between-group
comparisons showed significantly more boys with DMD were rated as having social behavior problems than
either the sibling or CP comparison groups. In addition to the increase in reported behavioral problems likely
related to the effects of chronic illness, boys with DMD may be at heightened risk for specific social behavior
problems. The specificity of the findings of the behavior profile in DMD may be partially due to the lack of
dystrophin isoforms in the central nervous system, and not solely a reactive response to the illness. J Dev
Behav Pediatr 27:470Y476, 2006.

Abnormalities in brain biochemistry associated with lack of dystrophin:
studies of the mdx mouseCaroline Raea,*, Julian L. Griffina,1, Duncan H. Blaira, John H. Bothwellb, William A. Bubba,
Annie Maitlanda, Stewart Headc
aDepartment of Biochemistry, The University of Sydney, Sydney, NSW 2006 Australia
bDept of Biochemistry, The University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
cSchool of Physiology and Pharmacology, The University of NSW, Sydney, 2052 Australia
Received 6 March 2001; received in revised form 12 June 2001; accepted 21 June 2001
Abstract
Biochemical abnormalities have been reported in dystrophin-deficient muscle of boys with Duchenne (severe Xp21) muscular dystrophy
or in the murine (mdx) model of the disease. These abnormalities include altered energy metabolism and responses to osmotic shock. In
contrast, the situation in brain is less well understood and it is probable that dystrophin is playing a different role (or roles) in this organ. In
this study we conclude that the elevation in choline-containing compounds reported in mdx brain is confined to cerebellum and hippocampus
in older (. 6 months) mice. We report alterations in glucose metabolism in mdx brain under normal, awake conditions, and a reduced
response of brain metabolism to the g-aminobutyric acidA receptor agonist muscimol. Using brain cortical slices we found no difference in
the response of dystrophic tissue to hypoosmotic shock, but increased, substrate-dependent oxygen consumption rates at low oxygen partial
pressures. .

P37.25 Central nervous system involvement in Duchenne
muscular dystrophyV. Yayla 1, A.E. Oge 2, K.S. Akca 2, A. Gokyigit 2,
H. Gurvit 2, Y. Parman 2, F. Deymeer 2, P. Serdaroglu 2
1 Haseki Educational and Research Hospital, Neurology,
Turkey
2 Istanbul University Istanbul Faculty of Medicine, Neurology,
Turkey
Background: The debate about the presence of brain
involvement in Duchenne muscular dystrophy (DMD)
has been continued since the first description of the disease.
Recent studies suggest that dystrophin levels are reduced at
the postsynaptic regions in CNS, along with morphological
and functional alterations of GABAA receptors.
Aim: To study the probable GABAA related cortical
excitability changes with electrophysiological means, primarily
by transcranial magnetic stimulation (TMS).
Methods:
Cases: Sixteen DMD boys, 10 healthy boys (CC) and 10
healthy adult volunteers (AC).
Electrophysiological tests: NCV and F wave studies of
the left ulnar nerve, motor evoked potentials (MEP), cortical
silent periods and cortical excitability with paired
TMS were studied by recordings from the left first dorsal
interosseous muscle. Standard electroencephalograms
(EEG) were evaluated as an additional electrophysiological
test.
Neuropsychological tests: WISC-R, California Verbal
Learning Test, Visual Memory Test, Color Trial Making
Test, and Verbal Fluency Test.
Results: There was no significant difference between
DMD and CC groups except the lower amplitude CMAPs
and MEPs in the DMD cases. On the other hand, intracortical
inhibition was absent and SP durations were shorter in
both the DMD and CC groups as compared to the AC
cases. EEGs showed mild generalized disorganization in
one fourth of the DMD patients. Neuropsychological tests
suggested a specific profile of cognitive impairment more
than a global dysfunction.
Conclusion: In this study, no significant cortical excitability
change was found in DMD patients who showed
the specific pattern of the normal childhood. EEG and neuropsychological
tests may be more sensitive in showing the
CNS involvement of DMD.

[David Feder]

Children could present some symptoms because DMD or because other causes: emotional problems, attention deficit disorder. Neurologic and/or psychological evaluation can elucidate this problem. The best way to find out the type of MD is DNA study.
David

[lia]

thanku so much for yr help..
thanks for all the efforts...

[Pediatric Cardiologist]

We have to be careful and not started medications on the DMD boys or for that matter any patients without having good data or ways of following the benefits. All medicine have side effects it is the matter of how much benefit one gets compared to the side effect. Obviously we hope for great benefit with little side effects. Our DMD boys now have doctors who really care for them and want to help make them better if not cure them. It will take time, cooperation, innovation and unfortunately money to make it happen. I very much have an interest in helping define the natural history of the DMD boys and only when we know what happens to them can we start effective trials and only when we have a useful tool. Best of luck to all.

[David Feder]

I partly agree with your opinion and I don't recommend or stimulate self-medication; I agree that clinical trials are essential and will clearly decide the merits of each treatment. But unfortunately this waiting does not help the current generation of patients, especially those who are older. For example the first study of steroids in DMD was in 1990 and only after more than 15 years the American Academy of Neurology decided to recommend this therapy. The complete study of losartan will take more than 10 years. How will the clinical condition of these boys? Whereas until this moment cardiac dysfunction in DMD is inevitable why not recommend the use of losartan as cardioprotective drug until the studies could happen?