How long did it take to obtain this marketing authorisation?
It is now ten years since I undertook the task of facilitating the availability of 3,4-DAP. In France, treatment of LEMS has been based on guanidine for a long time, with severe toxicity notably at the haematological and renal level. 3,4-DAP is a much less toxic product with proven efficacy and has already been used in many countries. Therefore, as a clinician, I saw that there was an absolute need to change treatment for my patients and I acted as a spur to the regulatory authorities to raise awareness and assist them in their efforts to obtain marketing authorisation.

Centronuclear myopathies (CNM) are a group of congenital myopathies classically defined by the presence of an abnormally high number of muscle fibres with nuclei organised in rows in the central part of the fibre. In addition to the increased central nuclei, DNM2-related CNM is characterised histologically by type 1 fibre. To date 18 different mutations in DNM2 have been reported, 10 of which are associated with CNM. In this study, the authors, including researchers from the Institute, describe an additional 12 patients from eight families with DNM2-related CNM and two novel and five recurrent missense mutations in DNM2. They have identified a number of clinical and histopathological features that expand the reported clinical phenotype of DNM2-related CNM.

Acceleron Pharma is developing novel therapeutics that modulate the growth of cells and tissues, including muscle, bone, fat, red blood cells and the vasculature. Acceleron has announced the initiation of a phase 2 clinical trial of ACE-031 in Duchenne muscular dystrophy (DMD). ACE-031 is an investigational protein therapeutic designed to promote muscle growth and increase strength by inhibiting signalling of a cell surface receptor called the activin receptor type IIB (ActRIIB). An earlier phase 1 trial of the compound found that it promotes muscle mass and volume in healthy volunteers. The current trial is taking place in several sites in Canada and is a randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, tolerability and pharmacokinetics of ACE-031 in patients with DMD who are also on corticosteroids.
> Read the press release

The distal spinal muscular atrophies (or distal hereditary motor neuropathies, distal HMN) are a clinically and genetically heterogeneous group of diseases affecting motor neurons. To date, fifteen loci and eight genes have been identified as being associated with one form of this disease. In this article, researchers have shown that an X-linked form of distal HMN was due to mutations in the gene encoding the copper transporter ATP7A. This protein is already known to be involved in Menkes disease, leading to a copper deficiency. The two mutations identified in two men with distal HMN, one from a Brazilian family and the other from a North American family, affect a highly conserved domain of the AT97A protein but does not affect copper transport. Analyses performed on cultured fibroblasts originating from skin biopsies, showed no decrease in the synthesis of mRNA or the ATP7A protein itself. However, researchers have identified discrepancies in the location and intracellular movements of ATP7A. This study shows that mutations in the ATP7A gene may cause a distal HMN not associated with copper deficiency and suggests a role of this protein in the function and maintenance of motor neuron.

 

Kennerson ML, et al. Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. Am J Hum Genet. 2010 Mar 12;86(3):343-52. Epub 2010 Feb 18.

Young researchers with an interest in muscle disease are invited to take part in this year’s European Research Conference in Paediatric Neurology in Leuven, Belgium. The Research Conference is supported by the European Paediatric Neurology Society (EPNS) and welcomes researchers from across Europe. The programme is divided into working group sessions, and the neuromuscular group is keen to encourage applications from researchers in any area of muscle disease wishing to present their research to their peers. Presentations should focus on ongoing projects, including challenges faced and plans for future development. Applications are welcome from researchers in a range of related disciplines, including genetics and muscle imaging, and from those focusing on adult conditions as well as paediatric.
> For more details

This comprehensive volume surveys the molecular, cellular, hormonal, nutritional, medical and lifestyle strategies being tested and applied for the prevention, intervention and treatment of age-related diseases. With authoritative contributions not just from researchers in academic institutions and pharmaceutical and cosmeceutical industries, but also practicing clinicians of both mainstream and alternative medicine, demographers and bioethicists, this book provides unique scientific, ethical and social perspectives on the discussion of aging intervention. In addition, the latest technologies in development, which will have serious bearings on future aging interventions, are reviewed. Aging Interventions and Therapies is ideal for graduates and undergraduates in universities and medical and nursing colleges, as well as post-graduates researching different aspects of aging and anti-aging. The topics covered are also highly relevant for professionals in the pharmaceutical, cosmeceutical, nutrition and healthcare industries, and practicing clinicians looking for a reliable and up-to-date resource on aging intervention and therapy.

A position is available immediately for a motivated research assistant to join Professor Kay Davies’ group at the MRC Functional Genomics Unit. You will join an active research team working on the development of therapeutics for Duchenne Muscular Dystrophy. The project focuses on the exon-skipping approach, which is one of the most promising therapies for this disorder and will involve quantification using real time qPCR.

A post-doctoral position is available in the laboratory of Dr. Helen Makarenkova, Neurobiology Department, The Scripps Research Institute, La Jolla, CA, USA.
This position is to investigate the role of homeodomain transcription factor Barx2 in mouse muscle satellite cells and other myogenic progenitors during muscle development and regeneration.

1. In France, treatment of Lambert Eaton syndrome (LEMS) was based on which drug?
a) 3,4-DAP
b) guanidine
c) arginine
d) DDP- 4

 

2. Approximately how many individuals in the European Union can be assumed to be currently suffering from LEMS?
a) 4,000
b) 10000
c) 6000
d) 3000

 

3. Which pharmaceutical company has just commenced a phase 2 clinical trial in DMD patients?
a)  PTC Therapeutics
b) Acceleron Pharma
c) Prosensa
d) BioMarin

 

4. An X-linked form of distal hereditary motor neuropathies was recently found to be due to mutations in which copper transporter gene?
a) ATP7A
b) hCTR1
c) CCS
d) hCOX17

 

5. The therapeutic effect of Glatiramer acetate (GA) was investigated in the dy2J/dy2J mouse model of merosin deficient congenital muscular dystrophy. For which disorder has this drug been approved?
a) Alzheimer’s disease
b) Chronic Fatigue Syndrome
c) Myasthenia gravis
d) relapsing-remitting multiple sclerosis

 

Answers are here !

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