Where others have failed will Atl1102 succeed ?, page-75

There is a new presentation on the PPMD website that addresses the problem of inflammation created by micro-dystrophin. That's right, gene therapy is creating its own inflammatory storm that may mitigate the benefit of any increase in dystrophin production. We have previously talked about the issue on ANP threads and probably for some of us, have addressed the issue with management.

The webinar is Gene Therapy - Turning Obstacles into Possibilities and features a presentation by Dr Nagaraju. The discussion on the immune response to gene therapy is quite complex and involves both an analysis of humoral immunity to the adeno-associated virus [AAV] delivery but also the cell mediated response to the formation of new dystrophin. We must remember that gene therapy is not replacing the dystrophin gene but is delivering a micro-dystrophin gene that omits potentially key information in complex biological processes. The micro-dystrophin gene is also being delivered into an already damaged muscle matrix and inflamed microenvironment.

Its the second type of response that is of particular interest to our own discussion. Spoiler alert - the discussion doesn't mention ATL1102 and doesn't canvass the effect of targeting CD49d and barely touches upon the role of lymphocytes in inflammation. What it does do, however, is throw a spotlight upon the inflammatory response to the expression of new dystrophin that may potentially cause damage to the newly formed better performing muscle.

Uboy has raised the question of whether ANP will move forward with one big trial to include both EMA and FDA arms? I think it all depends upon who is connecting the dots. In an ideal world, one would like to move forward with the EMA trial to establish the dose [albeit we are in the ball park at 25mg per week] and confirm efficacy at the optimum dosage rate. There is a sense of urgency, however, in finding a treatment for Duchenne and the science and biology appear to be aligning with the mechanism of action for ATL1102. If the financial resources are made available there may be a quicker road forward for the Duchenne community by moving straight into combination trials.