Where others have failed will Atl1102 succeed ?, page-77

@George1972

We start off with the premise that gene therapy will elicit an immune response, including as you point out, a cell mediated response from killer T cells (CD4/CD8). It serves to demonstrate the naivety of the gene therapy approach that if we simply induce dystrophin production everything will normalise for boys with Duchenne. Dr Nagaraju makes the observation that the body will make an immune response to the dystrophin therapy because it hasn't seen it before i.e. the body doesn't recognise an AAV delivered micro-dystrophin and sets out to neutralise it. There is no point jumping up and down saying don't you know this is good for you. This is undoubtedly all covered off in Immunology 101.

What is needed, however, is a strategy to firstly recognise and then dampen down the immune response. I believe that you are correct in pointing to the significance of the need to block the cell mediated immune response (as well as the antibody response to viral vectors). We should be aware that Dr Nagaraju is the co-founder and board member for ReveraGen BioPharma. From a brief perusal, ReveraGen is developing Vamorolone as a safer alternative for corticosteroid treatment in DMD.

We expect that corticosteroids and ATL1102 could work synergistically in dampening the immune response to gene therapy. The ace up the sleeve of ANP, however, is the fact that it ATL1102 has demonstrated efficacy in driving functional improvements in muscle strength as well as positive changes at a cellular level irrespective of exon skipping or gene therapy.

I believe the science behind the presentation by Dr Nagaraju is very supportive of the role for ATL1102 in combination therapy.