Nemaline Myopathy Support Group

Research

Prof. Kathryn North (Australia)

Research interests

Professor Kathryn North - Head, Institute for Neuroscience and Muscle Research Neuromuscular disorders constitute one of the major causes of ongoing disability in childhood. Children with neuromuscular disorders have significant and worsening disabilities; many children are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The Institute for Neuroscience and Muscle Research was established to study inherited neuromuscular disorders such as the muscular dystrophies and staff work closely with the doctors and therapists of the Neurogenetics Clinics to ensure the laboratory discoveries today are translated into real answers for affected children and their families tomorrow. The Institute for Neuroscience and Muscle Research (INMR) has seven teams working on various aspects of bain, nerve and muscle disorders. * Skeletal Muscle and Athletic Performance * Disease Mechanism in Muscular Dystrophies and Membrane Repair for Therapy * Gene Discovery in Inherited Myopathies * Neurofibromatosis (NF): Education and Learning/Clinical Trials (Tumours of NF1 and NF2) * Clinical Trials and Quality of Life * Neuroimmunology * Neurosurgery The INMR is a multi-disciplinary team involving over 40 clinicians, research scientists, genetic counsellors, physiotherapists, occupational therapists and psychologists who care for over 1800 patients and their families. The questions we seek to answer are directly relevant to our patients - our clinical trials can be immediately incorporated into treatments and therapies and our diagnostic service provides families with accurate diagnosis and disease specific treatment. The integration of our clinical and laboratory research and the clinical interface with patients within a Hospital setting makes us unique. Scientists within the laboratory continue to excel, with many junior researchers receiving awards for their presentations at national and international conferences.

1997 : Nemaline myopathy : Current Concepts

K.N. North, N.G. Laing, C. Wallgren-Pettersson and the ENMC International Consortium on Nemaline Myopathy.
A paper written in 1997 by Dr. Kathryn North.

Makes very interesting reading, although a little hard going, since it is written for scientists. I can email this document in MS Word (.doc) (92k), Rich Text Format (.rtf)(831k) or plain text (.txt)(14k). Requests to David: davidmcd_@hotmail.com

L-tyrosine supplementation in nemaline myopathy

Nemaline myopathy usually presents in infancy or early childhood with weakness of the facial, bulbar, proximal limb and respiratory muscles. Bulbar dysfunction in nemaline myopathy causes swallowing difficulties and drooling, and may predispose to aspiration of oral secretions.

There is currently no curative treatment available for patients with nemaline myopathy. Treatment strategies are largely empirical and symptomatic. Of interest is the report that L-tyrosine therapy in an 11 year old boy with nemaline myopathy lead to a dramatic and reproducible improvement in muscle strength, appetite and weight gain. In addition within 48 hours of commencement of treatment there was a profound improvement in pharyngeal secretions and drooling (Kalita 1989).

Based on this report we have given a number of patients with nemaline myopathy dietary supplementation with L-tyrosine. We have recently reported our experience in five patients (four infants and one adolescent) (Ryan et al. 2008). All four infants were reported to have an initial decrease in drooling and secretions and an increase in energy levels. The adolescent showed improved strength and exercise tolerance. Importantly, we observed no adverse effects of treatment. These initial observations suggest that dietary tyrosine supplementation may improve bulbar function, activity levels and exercise tolerance in nemaline myopathy.

Tyrosine is a non-essential amino acid that the body normally derives from two sources, diet and the chemical breakdown of phenylalanine in the liver. Tyrosine is converted to L-dihyroxyphenylalanine (L-Dopa) by tyrosine hydroxylase. This forms the rate-limiting step in the synthesis of the catecholamines dopamine, norepinephrine and epinephrine. These compounds are important neurotransmitters and are involved in the regulation of motor co-ordination, behaviour, learning, memory, sleep-wake cycle regulation endocrine and visceral functions and arousal in adults. An exhaustive search of the medical literature has not revealed any side effects related to treatment with L-tyrosine using doses up to 300mg/kg/day.

The reason for the clinical improvements in patients with nemaline myopathy treated with L-tyrosine is not clear. It is possible that tyrosine directly dries up saliva to improve handling of oral secretions. It may act on the brain to increase "stamina" or may act on the peripheral muscle motor unit response to improve the efficiency of muscle function. Further studies in the mouse models of nemaline myopathy may provide insight into the mechanism of action. In the meantime - larger and placebo controlled clinical trials are needed to establish that L-tyrosine is truly effective in the therapy of patients with nemaline myopathy.

In the children we treated in Australia, we perform plasma amino acid analysis prior to treatment to exclude a coexisting disorder of tyrosine or phenylalanine metabolism. All children underwent baseline and follow-up testing of liver function, plasma amino acid levels, serum ammonia and full blood count. L-tyrosine was administered in powdered form or capsules (Musashi Australia). The optimal dose of tyrosine is unknown. In younger children we started at a dose of 250mg- 500mg/day or 50mg/kg/day and increased the dose by 500mg at monthly intervals if we were getting a positive reponse with no side effects.

References

Kalita D. A new treatment for congenital nonprogressive nemaline myopathy. Journal of Orthomolecular Medicine 1989;2:70-74.
Ryan MM, Sly C, Rudge S, Ellaway C, Ketteridge D, Roddick LG, Iannaccone ST, Kornberg AJ, North KN. Dietary L-tyrosine supplementation in nemaline myopathy. J Child Neurology 2008 Jun;23(6):609-13.

Results

Five patients (four infants and one adolescent) were treated for periods ranging from two months to 5 years with tyrosine doses of 250-3000 mg/day (Table).

Other links for l-tyrosine.

University of Maryland Medical Center

Scientific paper published in 2011
Hypertrophy and dietary tyrosine ameliorate the phenotypes of a mouse model of severe nemaline myopathy.

Brief notes on other drugs and supplements taken by people with NM

Sydney Medical Institute

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Sydney Medical School
Edward Ford Building A27
The University of Sydney
NSW 2006
AUSTRALIA

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Supporting MAP Nemaline

In 2010 Meriel (aged 21 months) was diagnosed with Nemaline myopathy, a very rare muscle condition with no treatment or cure, which changed the lives of her family overnight. Setting up a family fund like MAP Nemaline is a great way to fundraise for Muscular Dystrophy UK to keep our vital research moving forward.

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