New Therapies For Rett Syndrome

J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic) Mosawi et al.
NEW THERAPIES FOR RETT SYNDROME
Aamir Jalal Al Mosawi
Children Teaching Hospital,Baghdad Medical City,Bab Al Muadham,Baghdad, Iraq
ABSTRACT
There is no satisfactory therapy for Rett syndrome, a rare genetic disorder. A three-year old
girl with Rett syndrome was hypotonic, ataxic, and had abnormal movements of the upper
limbs. She was unable to sit alone on a chair and showed no eye contact and was not
responding to her name. She didn’t have purposeful hand movement and was not able to
hold things. She couldn’t be held erect in the standing position. She was not saying any word
nor was babbling. The girl received two treatment courses. The first course included
intramuscular cerebrolysin 1ml daily for ten days. The second course included 10 cerebrolysin
injections, 3ml every third day, and oral citicoline. After the ten-day course of cerebrolysin,
she showed dramatic improvement in muscle tone and was able to sit on a chair, and she
had no abnormal movements. It was also possible to hold her straight in the standing position
without apparent ataxia. After the second course of treatment she showed marked
improvement with the development of purposeful movement and the ability to hold feeding
bottle with assistant of the mother and feed herself. She was able to stand and step one
step holding furniture. She started babbling and showed some reduction in the autistic
features. The use of these new therapies in Rett syndrome resulted in an obvious
improvement that has never been reported before.
Key words: Rett syndrome, cerebrolysin, citicoline.
No: of Figures : 03 No: of

References:12
2019 May Edition |www.jbino.com | Innovative Association

J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic) Mosawi et al.,
INTRODUCTION had history of convulsions and was taking

sodium valproate. She also had poor
Rett syndrome is a rare X-linked dominant feeding and respiratory abnormalities with
genetic disorder affecting only girls. The intermittent periods of apnea associated
disorder is generally regarded as a with cyanosis.The girl was not able to sit
neurodevelopmental condition rather than alone on the chair and showed no eye
a neurodegenerative disorder. The contact and was not responding to her
diagnosis is generally based on clinical name (Fig.1).
findings which characteristically include
(Galli et al.,1985; Peters, 1985):Delayed She didn’t have purposeful hand
motor development and delayed speech movement and was not able to hold things.
development.Ataxia or fine tremor of hand She was hypotonic and ataxic, and had
movements.Repetitive hand-wringing abnormal movements of the upper
movements and loss of purposeful and limbs.She couldn’t be held erect in the
spontaneous use of the hands. Autistic standing movement, and she was not
feature is a typical finding in all patients. saying any word nor was babbling.
Audiogram showed normal hearing. Brain
Generalized tonic-clonic convulsions occur MRI showed mild ventriculomegaly.
in the majority and are usually well
controlled by anticonvulsants. The girl was initially treated with cerebrolysin
Many patients also develop respiratory 1ml daily given by intramuscular injections
abnormalities with intermittent periods of for ten days.A second course of treatment
apnea that may be associated with given over one month included:
cyanosis.Feeding problems and poor
weight gain are common. Rett syndrome Cerebrolysin 3ml given by intramuscular
was most probably first described in injections every third day, received ten
German language in 1966 by Andreas Rett, doses.Oral citicoline 2ml (200mg) daily.The
a pediatrician in Vienna (Rett,1966) . protocol for this research was approved by
the scientific committee of Iraq
Bengt Hagberg, a Swedish pediatrician, headquarter of Copernicus Scientists
published an English article in 1983 and International Panel and conforms to the
named the condition after Rett (Hagberg et provisions laid out in the Declaration of
al.,1983).More than half century after the Helsinki (as revised in Edinburgh 2000).
syndrome was first described, and there is
no known effective therapy that can Results and Discussion
improve Rett syndrome, and treatment
mostly includes anticonvulsants to control After the ten-day course of cerebrolysin, the
seizures. girl showed dramatic improvement in
muscle tone and was able to sit on a chair
Patients and methods (Fig. 2), and she had no abnormal
movements or apparent ataxia. It was also
A girl with Rett syndrome was first seen at possible to hold her straight in the standing
the age of about three years because of position.After the second course of
developmental delay, abnormal treatment she showed marked
movements, and autistic features. The girl improvement:She developed purposeful

movements and was able to hold feeding speech, fine motoring, playing). Positive
bottle with the assistant of her mother and effects were noted in all the patients with
fed herself (Fig. 3). Asperger's syndrome and in 89% of the
patients with childhood autism.
She was able to stand and step one step
holding furniture (Fig. 3).She started Treatment was not associated with any side
babbling.She showed some reduction in effect (Krasnoperova et al., 2003).Radzivil
the autistic features according to the and Bashina (2006) described an open
mother, but at the clinic she remained not prospective clinical study of the use of
responding to her name and didn’t show cerebrolysin with a beneficial effect in the
obvious eye contact.There is no specific nor treatment of twenty five patients with
satisfactory therapy for many of the childhood autism.Chutko et al (2017)
disabling neurological disorders such as Rett reported that the use of cerebrolysin in the
syndrome. treatment of forty three children with autism
spectrum disorders was associated with
Cerebrolysin solution which can be given improvement observed in 27 patients
intramuscularly consists of low-molecular- (62.8%).
weight neuro-peptides including nerve
growth factor, glial cell line-derived Cerebrolysin can improve brain functions
neurotrophic factor, brain-derived through (Al Mosawi , 2017) :Inhibition of
neurotrophic factor, and ciliary apoptosis.Stimulation of neurogenesis
neurotrophic factor.Cerebrolysin solution is through stimulating proliferation,
a safe, well-tolerated, and efficacious differentiation, and migration of adult
neuroreparative agent that is associated subventricular zone neural progenitor stem
with a relatively wide therapeutic time cells.Stimulation of stem-cell proliferation in
window (Al Mosawi , 2017). the brain.Citicoline (cytidine diphosphate-
choline) or cytidine 5 diphosphocholine is a
Previous reports of the use of cerebrolysin in nootropic agent with a very low toxicity and
patients with Rett syndrome suggested that has been approved for treatment of head
it can improve behavior, attention level, trauma, stroke, and neurodegenerative
motor functions, and nonverbal social disease in Japan and Europe (Al Mosawi ,
communication. 2017).As a safe neuro-protective agent,
citicoline may improve brain functions
The EEG parameters of the patients with through the following mechanisms (Al
Rett syndrome could also be normalized Mosawi , 2017):
with the use of cerebrolysin
(Gorbachevskaya et al.,2001).The use of Preservation of cardiolipin and
cerebrolysin in childhood autism and autism sphingomyelin Preservation of arachidonic
spectrum disorder was also associated with acid content of phosphatidylcholine and
a beneficial.Krasnoperova et al., (2003) phosphatidylethanolamine.Partial
reported the use of cerebrolysin in the restoration of phosphatidylcholine
treatment of nineteen children with levels.Stimulation of glutathione synthesis
childhood autism and eight with Asperger's and glutathione reductase
syndrome. Treatment with cerebrolysin was activity.Reduction of phospholipase A2
associated with improvement of cognitive activity.Increasing glucose metabolism in
functions (expressive and receptive the brain.Increasing cerebral blood

flow.Reducing oxidative stress and release of free fatty acids and reducing
preventing excessive inflammatory blood brain barrier breakdown.
response in the brain by inhibiting the
Fig.1: A three-year old girl with Rett syndrome. The girl was not able to sit alone on
a chair and showed no eye contact and was not responding to her name.
Fig. 2: After the first course of cerebrolysin, the girl showed dramatic improvement
in muscle tone and was able to sit on a chair

Fig. 3: After the second course of treatment, the girl was able to hold feeding bottle
with the assistant of her mother and fed herself. She was able to stand and step one
step holding furniture

Enhancing cellular communication by Peters AC.The Rett syndrome. Tijdschr

increasing the availability of Kindergeneeskd 1985 Dec;53(6):232-4.
neurotransmitters, including acetylcholine, PMID:4095698 [Article in Dutch].
norepinephrine, and dopamine.Lowering
increased glutamate concentrations and Rett A. On a unusual brain atrophy
increasing the decreased ATP syndrome in hyperammonemia in
concentrations induced by childhood. Wien Med Wochenschr 1966
ischemia.Increases dopamine receptor Sep 10;116(37):723-6. PMID:5300597 [Article
densities. Al Mosawi (2019) reported a in German].
retrospective observational study
describing the use of cerebrolysin and Hagberg B, Aicardi J, Dias K, Ramos O.A
citicoline for the treatment of eight of 19 progressive syndrome of autism, dementia,
patients with autism and Asperger ataxia, and loss of purposeful hand use in
syndrome. Seven patients had autism and girls: Rett's syndrome: report of 35 cases.
one patient had Asperger syndrome. Ann Neurol. 1983 Oct;14(4):471-9.
PMID:6638958.
All the treated patients showed
improvement and marked lessening of the Al Mosawi AJ. A novel therapeutic
autistic features with six patients showed approach for the treatment of brain
complete disappearance of the main atrophy (ed). LAP Lambert Academic
autistic features. No patient developed any Publishing, Germany, 2017.
side effects. The eleven patients observed
during the same year who didn’t receive Gorbachevskaya N, Bashina V, Gratchev V,
this treatment or were treated with other Iznak A. Cerebrolysin therapy in Rett
treatments such as omega-3 and syndrome: clinical and EEG mapping study.
risperidone didn’t show any lessening effect Brain Dev 2001; 23 Suppl 1:S90-S93.
in the autistic features. However, one
patient was treated with citicoline injection Krasnoperova MG, Bashina VM, Skvortsov
showed obvious improvement in the autistic IA, Simashkova NV. The effect of
features. In this study, the use of cerebrolysin on cognitive functions in
cerebrolysin and oral citicoline in the childhood autism and in Asperger
treatment of Rett syndrome resulted in an syndrome. Zh
obvious improvement that has never been
reported before. Nevrol Psikhiatr Im S S Korsakova 2003;
103(6):15-8. PMID: 12872620 [Article
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References
Radzivil MG, Bashina VM. An effect of long-
Galli V, Ciccarone V, Venuta A, Ferrari P, term cerebrolysin therapy in
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Chutko LS, Yakovenko EA, Surushkina SY, Korsakova 2017; 117(9):71-75. PMID:
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J Bio Innov 2019; 8(1), pp: 99-108.

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J.Bio.Innov 8(3), pp: 301-307, 2019 |ISSN 2277-8330 (Electronic) Mosawi et al.

NEW THERAPIES FOR RETT SYNDROME

Aamir Jalal Al Mosawi

Children Teaching Hospital,Baghdad Medical City,Bab Al Muadham,Baghdad, Iraq

Key words: Rett syndrome, cerebrolysin, citicoline.

No: of Figures : 03 No: of

2019 May Edition |www.jbino.com | Innovative Association

INTRODUCTION had history of convulsions and was taking

2019 May Edition |www.jbino.com | Innovative Association

2019 May Edition |www.jbino.com | Innovative Association

in muscle tone and was able to sit on a chair

2019 May Edition |www.jbino.com | Innovative Association

2019 May Edition |www.jbino.com | Innovative Association

Enhancing cellular communication by Peters AC.The Rett syndrome. Tijdschr

2019 May Edition |www.jbino.com | Innovative Association

2019 May Edition |www.jbino.com | Innovative Association

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