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15th Annual Meeting Of The Oligonucleotide Therapeutics Society (OTS) Oct. 13-16th Munich, GermanyFollow along on twitter with either twitter ID "OTSociety" or timozark's favorite twitter id "oligogirl". Speaker on Wednesday Oct. 16th Session VIII: Oligonucleotide Preclinical Stage Development Elizabeth Vroom Wednesday, 16 October 11.50-12.15 The Role of Patient Organisations in Drug Development: The example of Duchenne Muscular Dystrophy Elizabeth Vroom World Duchenne Organization Duchenne parents decided to shoulder responsibility and become an active partner in the development of viable treatments or a cure for this disease. Duchenne parents worldwide have played a significant role not only as funders of research or the initiative for start-up companies, but also in raising awareness, improving care, setting up standards of care and the dissemination of this information. Furthermore they took the initiative to collect data on patient and caregiver preferences, to develop outcome measures, including Patient Reported Outcome Measures, and bridge the so-called ‘Valley of Death’ in drug development. They focus on optimal (re)use of data and optimal trials design. They are involved in regulatory and HTA discussions and European policies." One of the poster abstracts on duchenne : "Improving antisense oligonucleotide therapeutic applications: development
of a novel antibody-mediated delivery system
Ona Navikaite1, Philip Noble2,Terry Baker2, Daniel Lightwood2 Linda Popplewell
Royal Holloway University of London,
UCB Pharmaceuticals
A number of therapeutic antisense oligonucleotides (AOs) applications have been developed as promising candidates for sever e and devastating conditions such as Duchenne muscular dystrophy (DMD). DMD is a lethal, X -linked inherited disorder characterized by progressive muscle weakness, wasting and degeneration. AOs can be used to modulate dystrophin pre-mRNA splicing in a manner that restores the reading frame of the DMD transcript, producing a shorter but functional dystrophin protein (approach approved by FDA in 2016).
Nonetheless, one of the major challenges for successful AOs therapy in patients remains poor delivery and uptake in targeted tissues and cellular compartments. In order to address this issue,we designed and developed a novel antibody-mediated AO delivery system. A cell penetrating antibody was used as a carrier molecule for morpholino AOs (PMO) for targeted muscle specific delivery. We have explored several conjugation and purification strategies, and conducted a number of screenings in vitro to assess antibody -PMO conjugate functionality.
Our preliminary results confirm that antibody-PMO conjugate retains its function to penetrate differentiated myotubes. However, pre -mRNA splicing might be affected by steric interference of the antibody on RNA splicing machinery. Consequently, we are currently developing an alternative conjugation approach to facilitate PMO release following targeted myotube penetration. If successful, this antibody -PMO delivery system could improve overall PMO efficacy in DMD and other muscle related disorders.
Ona Navikaite, PhD student
Royal Holloway, University of London
School of Biological Science,
Egham, Surrey
United Kingdom |
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