Dedicated to the heart, the second day of Myology 2008 opened with the contributions of international experts such as the American, Kenneth Chien (Boston, USA) and the French researchers Michel Pucéat and Christelle Monville of I-Stem (Institute fro Stem cell Therapy and Exploration of Monogenic diseases, inaugurated in September and financed by the AFM).

Embryonic stem cells to repair the heart – from rat to monkey (Michel Pucéat)

Michel Pucéat (I-Stem, Inserm/AFM/UEVE, Evry) presented his team’s most recent advances in the use of human embryonic cells in the treatment of myocardial infarction. Since their work on the rat (Stem Cells, June 2007), the researchers have made progress by experimenting their therapeutic strategy on a model far closer to man – monkeys, presenting with a slight myocardial infarction. Also, they were able to note the differentiation of embryonic cells into cardiac cells (cardiomyocytes) and above all the total absence of any tumoral development in the heart or in other organs. A new step has been taken with the use of embryonic cells in heart therapy.



A new in vitro model for testing heart therapies (Christelle Monville)

In partnership with Michel Pucéat’s team, Christelle Monville (I-Stem, Inserm/AFM, UEVE, Evry) has developed an in vitro (known as organotypic) heart model. Several days after their culture and during the three months of the experiment, heart slices beat spontaneously and regularly. Moreover, the frequency of these heartbeats is increased by adrenaline, clearly demonstrating the validity of this model upon which it is now possible to test drugs. Furthermore, this model has been used by Michel Pucéat’s team for cell therapy.

Melatonin boosts heart cell therapy (Angelo Parini)

Angelo Parini (Inserm U858, Toulouse) presented his team’s work using mesenchymatous stem cells. These adult stem cells are at the origin of bone, cartilage and fatty tissue but can also produce other cell types, in particular skeletal or cardiac muscle cells. After noting that – following transplantation into the heart or kidney of animal models more than 80% of the transplanted cells died due to oxidative stress – the researchers endeavoured to increase their viability. They added melatonin (known for its strong anti-oxidative properties and widely used in humans) to the mesenchymatous cells in culture, thus protecting them from oxidative stress. Once transplanted into the myocardial infarcted rat hearts, these melatonin-treated cells lived longer and led to an improvement of the cardiac function.  




Nanoparticles – a new mode of administration fro exon skipping (Alessandra Ferlini)

Nanoparticles can become useful vectors for administering antisense oligonucleotides, those molecules that allow the erroneous parts of the dystrophin gene that cause Duchenne muscular dystrophy to be “skipped.” Alessandra Ferlini’s team (University of Ferrare, Italy) has shown that particles of polymethyl methacrylate – a biocompatible material of about 400 nanometres in diameter (400 millionths of a millimetre) – can be adsorbed by a very small dose of oligonucleotides. When administered to mouse models of Duchenne disease, they are capable of transporting the treatment directly to the heart and skeletal muscle cells and partially restore dystrophin production – even 60 days after injection in the case of the skeletal muscles. On the other hand, the same injected dose of naked oligonucleotides had no effect. The scientists are at present working to make these new vectors even more effective.

Myozyme® and adult Pompe disease – encouraging results to be confirmed

Within the framework of the Genzyme symposium organised on the Wednesday evening of the Myology 2008 congress, Pascal Laforêt (Institute of Myology, Paris) presented for the first time/in preview the results of an international trial on the treatment of adult Pompe disease with Myozyme®. This drug – developed by the biotechnology company Genzyme – is a human recombinant enzyme (alpha alglucosidase) capable of replacing the acid alpha-glucosidase (AAG) enzyme, deficient in persons affected by Pompe disease.
This phase II/III multicentric international control vs placebo therapeutic trial evaluated the effectiveness of an 18-month treatment on 90 patients with a moderate form of adult Pompe disease. On the whole, preliminary results show that Myozyme® stabilised disease progression. The two main criteria of evaluation – distance walked over 6 minutes and vital capacity – were significantly increased in the Myozyme®-treated group. However, there was no significant difference between Myozyme® and placebo for the other evaluation criteria. Only moderate side-effects were observed in both groups, except for an allergic reaction in 3 Myozyme®-treated patients, who had to abandon the trial. To decide on the true effectiveness of Myozyme® on adult Pompe disease, Pascal Laforêt emphasised that we must wait to see if the condition of the placebo group patients improves over the next six months, when they take the Myozyme® treatment.


Progeria : setting up a clinical protocol

On Wednesday afternoon Nicolas Lévy (Inserm, Marseille) announced the setting up of a clinical protocol concerning a rare disease of accelerated ageing, progeria.
This trial, which should involve 25 children in Europe, will allow researchers to test the effectiveness of the combination of two existing molecules in order to slow down the progression of this incurable disease which leads to death before the age of 15 years. Since the Marseille team identified the gene in 2003, five years have been sufficient for the researchers to understand the physiopathological mechanisms of the disease (accumulation of a toxic protein in the cell), to identify a therapeutic lead which aims to diminish or suppress the toxic effect and to carry out preclinical tests in the mouse.

Progeria is a laminopathy, caused by a defect of the LMNA gene coding the lamins A/C. Since the discovery of the involvement of this LMNA gene in Emery-Dreyfus muscular dystrophy in 1999, more than 10 hereditary diseases affecting different tissues have been identified as directly or indirectly linked to lamins A/C dysfunction – a form of peripheral neuropathy (Charcot-Marie-Tooth disease type 2B1), a form of limb-girdle myopathy (LGMD 1B), a form of familial partial lipodystrophy, a form of mandibulo-acral dysplasia, premature ageing diseases (progeria, Hutchinson-Gifford syndrome), and – recently – new syndromes: heart-hand syndrome of Slovenian type and an atypical form of Werner syndrome.