Gene therapy on SMA mice with a-SMN

In 2006 an all-Italian study, led by prof. Giorgio Battaglia of Neurologic Institute "C. Besta" in Milan, in collaboration with Dr. Enrico Garattini of Institute “Mario Negri”, has allowed the identification of a novel protein involved in the genesis of SMA. All this we have already discussed extensively in an article and in a deepening.

To summarize briefly, please note that new protein, called a-SMN or axonal SMN, have ownership of the growing axons of the motor neurons, which means the extensions by which nerve cells of the spinal cord are able to operate our muscles. The discovery of this new protein has led the group directed by Giorgio Battaglia to hypothesize that the lack or reduction of a-SMN in SMA "put in crisis" motor neurons that no longer maintain functional their axons, with progressive muscle atrophy.

Based on this working hypothesis, the research team has begun a project to test a gene therapy on SMA transgenic mice, using viral vectors to carry a-SMN to motor neurons of the animal in vivo and determine whether the expression so obtained of a-SMN can restore them and work properly. The research project is carried out in collaboration with a group led by Patrick Aebischer, a leading European expert in gene therapy at the Swiss Federal Institute of Technology (EPFL) in Lausanne. To make this cooperation more effective, Dr. Veronica Setola, who has played a key role in the laboratory in Milan by Giorgio Battaglia, is now more than a year in Lausanne, where she is currently working on the project in collaboration with Dr. Chris Towne, under the supervision of Patrick Aebischer.

The study has received various funding, including that of Girotondo Onlus Association, founded by the mother of a SMA child and designed to raise funds to be allocated to scientific research; on the site of Association is available an intermediate report of Prof. Battaglia on the state of research, summarized as follows:-

In the first 9 months of the program we have synthetized (in Geneva) 3 different types of viruses AAV6 a particular serotype of adeno-associated viruses, which are not dangerous to humans and does not induce an immune response into the recipient, containing a construct expressing the protein FL-SMN native (ie, the protein already known since 1995), the protein a-SMN native (ie the protein discovered in Milan) and the GFP protein (as control vector). The viruses AAV-6 thus obtained were injected into control mice with encouraging results. Indeed, after intramuscular injection and a survival time of approximately 1 month, both the viral control vector AAV-6/GFP and viral vectors containing protein FL-SMN and a-SMN are able to trasduce muscle and corresponding spinal motor neurons (ie able to be transported from muscle to the spinal cord, and go to "load" the motor neurons with the SMN protein). This is a very positive outcome, because it demonstrates the feasibility of the therapeutic protocol chosen, ie the possibility to genetically modify the motor neurons after intramuscular injection. The project is being carried out in parallel between Lausanne and Milan. In Lausanne, the SMA II mice are injected, with more severe clinical phenotype and very short survival of about two weeks. In parallel, in Milan are injected SMA III mice, with milder clinical phenotype and survival of approximately 1 year. The timing of the trial is necessarily long, how long is the road that may lead to the implementation of this protocol to the children affected. The data obtained are still too preliminary, but the first small step was taken, and all we hope it is a really important step.

This research has also obtained a grant from the Onlus Smarathon, born about a year ago by the will of the parents of a little girl affected from SMA, fans of sports and in particular marathon. Thanks to their fundraising the remarkable sum of 35,000 euros has been delivered into the hands of prof. Battaglia.

Read the original study on a-SMN

Read the intermediate report of prof. Battaglia on the new study (italian)