Medium-term open label trial of L-carnitine in Rett syndrome

University of Western Australia, Perth City, Western Australia, Australia
Brain and Development (Impact Factor: 1.88). 12/2001; 23 Suppl 1(1):S85-9. DOI: 10.1016/S0387-7604(01)00346-1
Source: PubMed


Treatment strategies in Rett syndrome so far have been essentially symptomatic and supportive. In order to establish the medium-term effects of L-carnitine, an open label trial was performed in a cohort of 21 Rett syndrome females, with a control group of 62 Rett syndrome females of a similar age, for a 6-month period. Compared with the Rett syndrome controls, treatment with L-carnitine led to significant improvements in sleep efficiency (P=0.027), especially in the subjects with a baseline sleep efficiency less than 90%, energy level (P<0.005) and communication skills (P=0.004). There was no significant difference in the subject's level of physical activity, hand function or in the quality of life of the subject's parents. In addition, before and after comparisons of the treatment group showed improvements in expressive speech (P=0.011). Treatment with L-carnitine seems to be of significant benefit in a subgroup of girls with Rett syndrome. In these girls, small but discernible improvements may be of considerable importance to their parents and carers.

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    • "ALC improves motor and cognitive deficits in several disease models [24], [25] through a variety of mechanisms including increased acetylcholine synthesis and neurotrophin expression, as well as improved mitochondrial function [26]. Clinical trials of ALC and L-carnitine, another carnitine derivative, in older RTT girls (median ages between 6 and 10 years old) report modest improvements in sleep, energy level, communication, and cardiac function [27], [28], [29]. The modest improvements noted in these clinical trials suggest some clinical efficacy; however, the timing of the treatment may be unable to reverse the myriad of neurochemical and structural abnormalities in an already symptomatic child. "
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    ABSTRACT: Rett syndrome (RTT) is a devastating neurodevelopmental disorder affecting 1 in 10,000 girls. Approximately 90% of cases are caused by spontaneous mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Girls with RTT suffer from severe motor, respiratory, cognitive and social abnomalities attributed to early deficits in synaptic connectivity which manifest in the adult as a myriad of physiological and anatomical abnormalities including, but not limited to, dimished dendritic complexity. Supplementation with acetyl-L-carnitine (ALC), an acetyl group donor, ameliorates motor and cognitive deficits in other disease models through a variety of mechanisms including altering patterns of histone acetylation resulting in changes in gene expression, and stimulating biosynthetic pathways such as acetylcholine. We hypothesized ALC treatment during critical periods in cortical development would promote normal synaptic maturation, and continuing treatment would improve behavioral deficits in the Mecp2(1lox) mouse model of RTT. In this study, wildtype and Mecp2(1lox) mutant mice received daily injections of ALC from birth until death (postnatal day 47). General health, motor, respiratory, and cognitive functions were assessed at several time points during symptom progression. ALC improved weight gain, grip strength, activity levels, prevented metabolic abnormalities and modestly improved cognitive function in Mecp2 null mice early in the course of treatment, but did not significantly improve motor or cognitive functions assessed later in life. ALC treatment from birth was associated with an almost complete rescue of hippocampal dendritic morphology abnormalities with no discernable side effects in the mutant mice. Therefore, ALC appears to be a promising therapeutic approach to treating early RTT symptoms and may be useful in combination with other therapies.
    Full-text · Article · Dec 2012 · PLoS ONE
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    • "Secretin does not significantly improve sleep-onset delay, duration, bedtime resistance, and night wakings in children with ASD RCT, level III Excluded: not specified Sleep diary (bedtime, sleep onset, time/duration night waking, morning rise) Sleep-onset delay (Pre, mean: 2.1 [range: 1–3]; Post, mean: 1.6 [range: 1–3]) Night wakings (Pre, mean: 4.1 [range: 3–7]; Post, mean: 3.6 [range: 3–5]) Sleep duration (Pre, mean: 4.7 [range: 3–7]; post, mean: 4.3 [range: 3–8]) S110 MALOW et al by guest on September 13, 2015 Downloaded from TABLE 1 Continued Study and Grade Sample Intervention and Duration Measures Used to Arrive at Conclusion Results Conclusions Ellaway et al, 2001 43 "
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    ABSTRACT: Objective: This report describes the development of a practice pathway for the identification, evaluation, and management of insomnia in children and adolescents who have autism spectrum disorders (ASDs). Methods: The Sleep Committee of the Autism Treatment Network (ATN) developed a practice pathway, based on expert consensus, to capture best practices for an overarching approach to insomnia by a general pediatrician, primary care provider, or autism medical specialist, including identification, evaluation, and management. A field test at 4 ATN sites was used to evaluate the pathway. In addition, a systematic literature review and grading of evidence provided data regarding treatments of insomnia in children who have neurodevelopmental disabilities. Results: The literature review revealed that current treatments for insomnia in children who have ASD show promise for behavioral/educational interventions and melatonin trials. However, there is a paucity of evidence, supporting the need for additional research. Consensus among the ATN sleep medicine committee experts included: (1) all children who have ASD should be screened for insomnia; (2) screening should be done for potential contributing factors, including other medical problems; (3) the need for therapeutic intervention should be determined; (4) therapeutic interventions should begin with parent education in the use of behavioral approaches as a first-line approach; (5) pharmacologic therapy may be indicated in certain situations; and (6) there should be follow-up after any intervention to evaluate effectiveness and tolerance of the therapy. Field testing of the practice pathway by autism medical specialists allowed for refinement of the practice pathway. Conclusions: The insomnia practice pathway may help health care providers to identify and manage insomnia symptoms in children and adolescents who have ASD. It may also provide a framework to evaluate the impact of contributing factors on insomnia and to test the effectiveness of nonpharmacologic and pharmacologic treatment strategies for the nighttime symptoms and daytime functioning and quality of life in ASD.
    Full-text · Article · Nov 2012 · PEDIATRICS
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    • "There is a significant increase in theta frequency between the treated but not the untreated patients (Wilcoxon test). several pathologies associated with RTT, often the treatments have been oriented to control specific symptoms and clinical trials have been carried out during the years to assess the effects of several drugs for treating sleep efficiency, respiratory dysfunctions, or seizures [33] [34] [35]. However, the evidence is that benefits from tested therapies are limited. "
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    ABSTRACT: Rett syndrome (RTT) is a devastating neurodevelopmental disorder that affects one in ten thousand girls and has no cure. The majority of RTT patients display mutations in the gene that codes for the methyl-CpG-binding protein 2 (MeCP2). Clinical observations and neurobiological analysis of mouse models suggest that defects in the expression of MeCP2 protein compromise the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function, such as insulin-like growth factor 1 (IGF1), are good candidates for ameliorating the symptoms of RTT. IGF1 and its active peptide, (1-3) IGF1, cross the blood brain barrier, and (1-3) IGF1 ameliorates the symptoms of RTT in a mouse model of the disease; therefore they are ideal treatments for neurodevelopmental disorders, including RTT. We performed a pilot study to establish whether there are major risks associated with IGF1 administration in RTT patients. Six young girls with classic RTT received IGF1 subcutaneous injections twice a day for six months, and they were regularly monitored by their primary care physicians and by the unit for RTT in Versilia Hospital (Italy). This study shows that there are no risks associated with IGF1 administration.
    Full-text · Article · Jun 2012
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