Genotarget, a biotech startup and part of the Artgen Biotech ecosystem (MOEX: ABIO), has completed preclinical studies of a new gene therapy drug, GTDF102, for the treatment of muscular dystrophy - dysferlinopathy (LGMD R2, Miyoshi myopathy).
The studies were conducted in collaboration with the Belgorod State National Research University, with grant assistance from the Russian Ministry of Education and Science. The Research Institute of Human Morphology, Academician B.V. Petrovsky Russian Surgery Research Center, and Genetico Center also participated in the studies of the drug.
The studies conducted on mice with the disease model yielded promising results. The synthesis of normal dysferlin protein in an amount sufficient to improve muscle tissue condition was achieved. The preliminary findings of the study have been published in the International Journal of Molecular Sciences.
Once the data has been verified and expanded, the production process has been refined, and a package of documents has been assembled, Genotarget will submit a dossier to the Ministry of Health of the Russian Federation for authorization to conduct clinical trials of the drug with patients.
GTDF102 is a combination of two recombinant viral vectors based on adeno-associated virus. These vectors carry the coding sequence of the dysferlin gene, which is under the control of elements that ensure the targeted action of the drug in muscle. The dual viral vector delivers a full-length and fully functional gene encoding the dysferlin (DYSF) protein.
‘The gene that encodes the missing protein can be delivered into muscle cells in two ways: using adeno-associated viruses or plasmids. Both forms have been subjected to rigorous effectiveness and safety testing. At present, there is no drug on the market that treats LGMD R2 dystrophy,’ states Alexey Deykin, Ph.D in Biology, Director of the Joint Center of Genetic Technologies of the Belgorod State National Research University.
Since 2012, a scientific team has been developing a drug for the treatment of dysferlinopathy. The team consisted of scientists who later continued their research at Artgen Biotech and the startup Genotarget (a Skolkovo resident since 2018). In the initial phase, several candidate drugs were developed that could potentially be used for the treatment of this disease.
The proprietary codon-optimized cDNA of dysferlin formed the foundation for the development of GTDF102. During preliminary studies, GTDF102 was tested at the proof-of-concept level in cell lines and model animals. This was conducted in collaboration with experts from the Kazan Federal University, the Lopukhin Federal Research and Clinical Center of Physical and Chemical Medicine, the Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency of Russia, and Marlin Biotech LLC. The results were published in leading international scientific editions. Dysferlinopathy is a severe, progressive inherited disease of muscle tissue caused by mutations in the DYSF gene. This gene encodes the dysferlin protein, which plays a crucial role in muscle fiber recovery. Mutations in the DYSF gene result in the absence of dysferlin or a reduction in its activity. Due to impaired muscle cell recovery, patients experience rapid destruction of muscle tissue, with the replacement of muscle with fibrous and fatty tissue, resulting in severe disability at working age.
Dysferlinopathy is the second most prevalent from of dystrophy among limb-girdle muscle dystrophies. A conservative estimate suggests that there are no more than 1,000 patients in the Russian Federation.