This is interesting.
Dr Cathryn Clary said ".
.in fact what I did find out when I was in Orlando at PPMD is the treatment paradigm for DMD seems to be changing towards a lot more combination therapy....dystrophin restoration therapies such as gene therapy, exon skipping, corticosteroids and then other agents in the immunomodulatory area such as ATL1102.. they can be used together. So, we really do see a substantial role for our drug going forward if our studies turn out POSITIVE of course.
Here is an article:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902687/pdf/fgene-09-00114.pdf- Fibrosis, inflammation and muscle atrophy are among the most important complications associated with muscular dystrophy, and they can severely compromise the efficiency of gene or cell therapy by limiting access to the dystrophic muscle. Fibrosis can be defined as the increased expression and accumulation of Extracellular Matrix (ECM) proteins, such as fibronectin and collagen, which contributes to muscle dysfunction.
- A combined therapy is most often designed to treat the secondary consequences of the muscular dystrophy that decrease the efficiency of single therapies, e.g., inflammation, fibrosis, or degeneration.
Here comes to ATL1102. From George Tachas:
https://www.cgtlive.com/view/tachas-targeting-inflammation-dmd-antisense-oligonucleotides“
We're seeking to stop the secondary causes of damage to muscles in DMD, which is the inflammation. The primary cause is dystrophin that leads to the loss of a structural protein, but then when you use the muscles, they contract, they get damaged, and then the immune system goes, hang on, this shouldn't be here andit's further damage to them. So we're targeting the secondary cause of immune mediated damage in Duchenne.”
- Combined therapies should have a synergistic effect. It is essential to combine the positive outcomes of distinct therapies that target these different features to enhance therapeutic efficiency.
From PER announcement: (26-07-2023)
https://per.live.irmau.com/pdf/6c3c56e0-38a2-4326-bf90-982ddef2d817/Positive-new-DMD-Combination-Therapy-Data-in-mdx-mice.pdfDr George Tachas, the Director of Drug Discovery and Patents said “The Company continues to be encouraged by the positive EDL functional benefits observed with the ASO monotherapy and ASO dystrophin restoration combination therapy approach and by the new RNA observations in the quadricep indicating the underlining biological mechanisms with ASO monotherapy and
the apparent synergistic mechanisms observed in the combination.... These study results are exciting and suggest the potential for ATL1102 in combination with dystrophin restoration drugs to improve therapeutic outcomes in DMD patients”
- The early detection of dystrophin deficiency and a precise genetic diagnosis will allow the treatment to be started before the onset of fibrosis, chronic damage, and inflammation in the muscle. A genetic correction might then be enough to avoid the progression of the disease. However, the diagnosis for sporadic mutations is usually done when the patients start to show their first symptoms in early childhood and, at this moment, muscles already show extensive damage, inflammation and fibrosis. In this case, secondary effects of the gene deficiency should be addressed in combined therapies to enhance the correction of the genetic defect.
My gut feeling is that if the Phase 2B data readout is
POSITIVE... we will proceed to the ambulatory patients...
Listen to Dr.Voit comment from 46:06 marks onwards....
https://drive.google.com/file/d/1Kccnj7ZpDxNFSZJp7kq310XAFoGQmnHY/viewGood Luck Everyone...
