Gene therapy trials in 2007

[Andy]

Gene therapy Phase I trial in LGMD type 2B

www.mdausa.org/research/060908lgmd_gene_therapy.html

I also read somewhere that the french were going to start a Phase I trial of Gene therapy in LGMD type 2A next year

[David Feder]

I received this information about exon skipping in DMD - The Netherlands's trial



UPDATE ON EXON SKIPPING



Dear all,

Today Judith van Deutekom, Prosensa and LUMC Leiden, will present on the World Muscle Society conference in Brugge the preliminary results of the ongoing clinical trial in the Netherlands.

After intra muscular injection of AON skipping exon 51 in the first patiënt, they were able to demonstrate the presence of truncated Dystrophin in the biopsy which was taken earlier this week, one month after injection. So far 3 patients are injected without side effects.

Although more results will follow in the next month we felt you all might like to know this first information.

Kind regards,

Elizabeth Vroom
Amsterdam, October 2006
UPPMD

and

Pat Furlong, President
Parent Project Muscular Dystrophy

[hb]

hello Andy, the news i found was for LGMD 2D and not 2B.... please, if you have read anything about LGMD-2A/2B... then, i would be happy to hear about...

its been long my computer is not getting connected to this website, but i somehow could get into the board, while i still cannot see the home page.. but still the news in boards are interesting to follow and be in touch

hb

[David Feder]

www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17164775&query_hl=1&itool=pubmed_docsum

Phenotypic Correction of alpha-Sarcoglycan Deficiency by Intra-arterial Injection of a Muscle-specific Serotype 1 rAAV Vector

alpha-Sarcoglycanopathy (limb-girdle muscular dystrophy type 2D, LGMD2D) is a recessive muscular disorder caused by deficiency in alpha-sarcoglycan, a transmembrane protein part of the dystrophin-associated complex. To date, no treatment exists for this disease. We constructed recombinant pseudotype-1 adeno-associated virus (rAAV) vectors expressing the human alpha-sarcoglycan cDNA from a ubiquitous or a muscle-specific promoter. Evidence of specific immune response leading to disappearance of the vector was observed with the ubiquitous promoter. In contrast, efficient and sustained transgene expression with correct sarcolemmal localization and without evident toxicity was obtained with the muscle-specific promoter after intra-arterial injection into the limbs of an LGMD2D murine model. Transgene expression resulted in restoration of the sarcoglycan complex, histological improvement, membrane stabilization, and correction of pseudohypertrophy. More importantly, alpha-sarcoglycan transfer produced full rescue of the contractile force deficits and stretch sensibility and led to an increase of the global activity of the animals when both posterior limbs are injected. Our results establish the feasibility for AAV-mediated alpha-sarcoglycan gene transfer as a therapeutic approach.Molecular Therapy (2007) 15, 53-61.

[Andy]

Hi ... the information i found was on the genethon website.

After searching again for it the only information i can find about a clinical trial in 2007 is one for type 2C LGMD

w3.genethon.fr/php/layout_2.php?lang=us&navp=5&navt=rd&content=rd_strat&tools=0&subitem=rd_gammasarco

[Andy]

Also on this page of the genethon website i find this information

w3.genethon.fr/php/layout_2.php?lang=us&navp=5&navt=rd&content=rd_strat&tools=0&subitem=rd_calpai#3

CLINICAL PROJECT

The first limb girdle muscular dystrophy for which we obtained the proof of principle for efficacy of a AAV-mediated gene therapy approach is calpainopathy. Indeed, we showed that, after intramuscular or intrarterial injections of an AAV vector carrying the calpain 3 cDNA in mouse, the transgene expression was associated with a correction of the atrophy and an increase of muscle strength. We obtained in March 2006, from the European regulatory agency (EMEA), the orphan drug designation for this approach.

A clinical trial is currently being prepared with this gene therapy product. It is a phase I/IIa open-label dose escalation trial. Three doses will be tested and administration will be made by intramuscular injection. The aim of this trial is to evaluate the tolerance of this approach and the quality of gene transfer into patients muscle.