Distal myopathies

The 2nd ENMC workshop on distal myopathies was held in Naarden, The Netherlands, from 8th to 10th March 2002. It was attended by 26 active participants from Australia, Austria, Belgium, Finland, France, Germany, Israel, Italy, Japan, The Netherlands, Spain, Sweden, The United Kingdom and the U.S.A. The meeting reviewed the extensive scientific progress since its 1st workshop in 1994: All of the four previously clinically defined entities have reached the point of genetic definition by linkage assignment and some have been defined by their gene and causative mutations. In addition a large number of new disorders have been reported in single families in which linkage has been established or linkage to loci for the known distal myopathies has been excluded. Participants reported on three new genes involved in muscle diseases with marked distal wasting and weakness discovered during the last year. Titin was shown to be the causative gene for Tibial muscular dystrophy. Mutations in the GNE gene were reported in the so called quadriceps sparing myopathy and in the recessive distal myopathy with rimmed vacuoles (Nonaka type). Two mutations in a myosin gene were associated with childhood onset distal myopathy (Laing type). In seven other distal myopathies the localisation of the genetic cause to a certain chromosome has been achieved, awaiting further progress to find the gene. Clinical findings in a number of families with undetermined status regarding linkage were reported in detail. Many presentations extended the current concepts of distal myopathies including occasional atypical findings in patients with GNE, dysferlin and caveolin3 mutations and in patients with tibial muscular dystrophy. The known molecular causes of distal myopathies do not yet allow specific treatment. In order to expand the knowledge of basic mechanisms leading to progressive muscle cell loss in these diseases, more research is needed to identify disturbed protein interactions caused by the mutations. The participants established a large number of agreements on collecting further families and collaborating with the research groups doing molecular genetic studies on distal myopathies.

An extended report of this meeting is published in Neuromuscular Disorders, Volume 12, No.9, November 2002.

Dr. B. Udd (Finland)
Chairman

For further information contact:
European Neuromuscular Centre (ENMC)
Lt.Gen. van Heutszlaan 6
3743 JN Baarn
THE NETHERLANDS
tel. (31) 35 5480481
fax (31) 35 5480499
e-mail enmc@enmc.org

Designing rational therapy of SMA based on understanding of its pathophysiology

This meeting was attended by 23 participants from 7 countries.
New information was presented that could help in changing the consequences of the SMN gene defect on the phenotype of Spinal Muscular Atrophy (SMA).
Moreover various animal models of the disease, produced by manipulations that altered the genes of the mouse so as to resemble SMA human disease, were discussed.

Proposals as to how these animal models could be used to develop effective treatment of SMA were discussed.

The following questions were addressed:
How can a partial defect but not complete absence of SMN be responsible for neuromuscular malfunction?

Among various functions of the SMN protein, which one is producing the symptoms characteristic of SMA?

There are now efficient in vitro tests that could identify compounds which could repair the gene defect. The next challenge is to evaluate the potential benefit of some of the molecules which have been identified in vitro alone or in combination as beneficial on mouse models.

In addition a better understanding of factors that control motor neuron and muscle survival may lead to alternative and attractive therapeutic approaches.

Future research should cover methods of optimizing muscle function in these children as well as attempting to correct the molecular defect.

The participation of scientists from different fields and clinicians may lead to a more concerted effort to find rational therapy of the disease. It is hoped that complementary approaches communicated at the Workshop will lead to more rapid progress in achieving improved management and treatment of patients.

An extended report of this meeting is published in Neuromuscular Disorders, Volume 13, No. 2, February 2003.

Prof. G. Vrbová (London, UK)
Dr. J. Melki, (Paris, France)