MeiraGTx announces eight presentations at ESGCT

MeiraGTx announced the Company will exhibit eight posters and deliver one oral presentation at the European Society of Gene and Cell Therapy, ESGCT, 2023 Annual Congress, which is being held from October 24-27, 2023, in Brussels, Belgium. The details of the oral and poster presentations are below: Oral Presentation OR82: Preclinical Efficacy of AAV-hUPF1 with an optimized vector genome and novel CNS capsid: Gene Therapy for ALS and FTD. At 4.9 kb, the optimized hUPF1 construct is 1.5 kb smaller than the original, thus offering AAV packaging and manufacturing benefits while demonstrating greater efficacy. When tested in vitro, the optimized AAV-hUPF1 rescued toxicity in both the TDP-43 and C9orf72 iNeurons models, at lower MOIs than the original. Optimized AAV-hUPF1 also rescued the pathophysiology of neurons derived from C9orf72 patient cell lines. Furthermore, we developed a novel AAV capsid that expresses in neurons of both the brain and spinal cord when administered by ICM in mice. Poster #008: Results of a phase 1 open-label, dose escalation study of gene therapy with AAV2-hAQP1 as treatment for radiation-induced xerostomia and parotid gland hypofunction. AAV2-hAQP1 was safe and well-tolerated at all dose levels, with no treatment-related serious adverse events or dose limiting toxicity. At Month 12, 16 of the 24 participants had an improvement of greater than or equal to8 points in XQ score, and 18 of the 24 reported important improvement in xerostomia symptoms relative to baseline on the GRCQ. In bilaterally treated participants, the average percent increase in unstimulated whole saliva flow rate at Month 12 post-treatment relative to baseline was 82.1%. Poster #116: fDISCO evaluation of AAV mediated gene expression upon different routes of administration. Detection methods to assess gene transfer mediated expression of reporter proteins in tissue requires to dissect or slice the sample, during which the three-dimensional structure is lost. On the other hand, live imaging often does not provide enough resolution to identify reporter protein expression on a cellular level. Here, we have tested whether fDISCO could overcome these limitations. In conclusion, fDISCO is able to capture the complete histological information of fluorescent reporter signal, thus being a suitable method to study the AAV-mediated reporter expression on the cellular level in 3D tissue samples. Poster #122: Development of alternatives to Triton X-100 cell lysis for AAV2, AAV5 and AAV8 primary recovery. Triton X-100 is an effective detergent for recovering biological products from intracellular compartments, but its use is now prohibited by Registration, Evaluation, Authorisation and Restriction of Chemicals regulations as its degradation generates a compound that negatively impacts aquatic life. This study demonstrates two optimized alternative AAV release methods to substitute the use of Triton X-100 that showed comparable product recovery and product quality profiles.