Professor Mimoun Azzouz came to Elta House in December last year to give us an update on his research, which is supported by The Jennifer Trust. He told us about some groundbreaking results that would be announced worldwide in a paper due to be published in the following few months. This has now happened and the research paper Systemic Delivery of scAAV9 Expressing SMN Prolongs Survival in a Model of Spinal Muscular Atrophy was published in Science Translational Medicine on 10th June. The press release issued by Sheffield University said:
The research team at Sheffield, led by Professor Mimoun Azzouz, tested whether a novel gene replacement therapy through a single injection was the most efficient way to treat the disease in a group of mice. They found that the injection, which expressed the SMN gene, successfully restored the SMN protein to normal levels and alleviated symptoms in the SMA model.
The new technique has the potential to develop a simple injection, without any requirement for risky and costly surgical interventions, and has achieved the highest therapeutic effects reported in the field to date. This has significant implications for the future treatment of SMA.
Professor Mimoun Azzouz, from the University's Department of Neuroscience, said: "I am delighted by the outcome of several years of efforts to tackle this devastating disease. These results bring us one step closer to a successful gene therapy treatment for patients with SMA."
The abstract to the paper states that:
Spinal muscular atrophy is one of the most common genetic causes of death in childhood, and there is currently no effective treatment. The disease is caused by mutations in the survival motor neuron gene. Gene therapy aimed at restoring the protein encoded by this gene is a rational therapeutic approach to ameliorate the disease phenotype.
We previously reported that intramuscular delivery of a lentiviral vector expressing survival motor neuron increased the life expectancy of transgenic mice with spinal muscular atrophy. The marginal efficacy of this therapeutic approach, however, prompted us to explore different strategies for gene therapy delivery to motor neurons to achieve a more clinically relevant effect.
Here, we report that a single injection of self-complementary adeno-associated virus serotype 9 expressing green fluorescent protein or of a codon-optimized version of the survival motor neuron protein into the facial vein 1 day after birth in mice carrying a defective survival motor neuron gene led to widespread gene transfer. Furthermore, this gene therapy resulted in a substantial extension of life span in these animals.
These data demonstrate a significant increase in survival in a mouse model of spinal muscular atrophy and provide evidence for effective therapy.
Congratulations to all the researchers who have contributed to this piece of work. Jennifer Trust members will be able to hear more about it at Conference, because Chiara Valori has kindly agreed to be one of the keynote speakers, and will no doubt be happy to answer questions about the implications for practical treatments, outcomes, timescales, and plans for clinical trials regarding this very significant research. | 
