1. QUESTION:  Dr. Cossu, your research in dystrophic dogs has created a lot of excitement in the DMD community. Please summarize for us the method and results of this research.

COSSU: We reported that five consecutive intra-arterial injections of donor mesoangioblasts (vessel associated stem cells) resulted in maintenance of muscle structure and function in dogs affected by Duchenne muscular dystrophy. This protocol required continuous immune suppression. In contrast, similar injections of autologous mesoangioblasts, genetically corrected in culture with human micro-dystrophin did not yield comparable results despite widespread expression of micro-dystrophin.

2. QUESTION:  Can you comment on how these results in dogs could be correlated to humans, dog years vs. human years, and other species differences that could affect the outcome in humans.

COSSU:  Based on these results we are now planning a first trial in patients using donor mesoangioblasts from an HLA identical donor, under a regimen of immune suppression. Dogs are the model of muscular dystrophy closest to human disease and the positive results encouraged us to think that perhaps a similar outcome may be obtained in patients. Of course the lifespan of humans and dogs is different and we are now performing a long-term treatment in dogs, hoping to get information in significant time advance on the possible long-term situation that may be faced in patients, should the first trial yield a positive or partially positive outcome.

3. QUESTION:  From where did you retrieve the cells you used for this research?  How easy or difficult will it be to get these cells in sufficient quantity for human treatment?

COSSU:  Cells will be isolated and expanded in culture to the numbers needed from a small muscle biopsy performed on the donor. We have evidence that this number (approximately three billions) can be obtained from a standard muscle biopsy.

4. QUESTION:  CureDuchenne is pleased to provide a one year grant for your research. 
   Can you tell us how this funding might expedite your research?

ANSWER:  In order to proceed to a clinical trial, it is mandatory that the cell production is performed under clinical grade (GMP/GLP conditions). This is extremely costly and the grant from CureDuchenne will allow us to perform this procedure and obtain approval from the Italian Regulatory Authorities.

5. QUESTION: There has been some comments that the immunosuppressant drug you used, cyclosporine, might have played a role in the amelioration of DMD symptoms in the dogs. What was the previous research that you based your assumptions on and what will you do
   in the future to ensure the results are derived from the stem cells themselves?

COSSU:  The comments that appeared recently were based on a peculiar scanning of
the literature. Essentially the few papers reporting a beneficial effect of cyclosporine on the disease itself (that anyway were transient) were reported and emphasized whereas the more numerous papers reporting deleterious effects of cyclosporine on dystrophic muscle were ignored. In any case we have now four dystrophic dogs treated with cyclosporine only and the result of an ongoing clinical trial with cyclosporine will be available many months before the start of our trial. 

6. QUESTION:  Your research that CureDuchenne is funding is using adult stem cells.  Do you see these adult stem cells being easy to work with and capable of truly replacing dystrophin in DMD patients?

COSSU:  This is what we hope to show in patients. Not a definitive cure of course (if not else for the continuous need of cyclosporine) but a significant functional improvement. Additional improvements of the method and possibly combination with new drugs, currently being tested, may in the future lead to a more definitive treatment.

7. QUESTION:  Much of the research in DMD is aimed at dealing with the downstream secondary effects of dystrophin deficiency.  Your goal is to create dystrophin in our boys.  What do you need to move your work along as quickly as possible?

COSSU:  We need to address all the required regulatory procedures, to raise the money needed (but hopefully this should not be a major obstacle) and finally to learn about the final experiments in dogs. We are proceeding at our possible fastest rate: our hope would be to start early next year.