Critical limb ischemia is a clinical syndrome characterized by ischemic pain at rest and tissue loss, such as non-healing ulcers or gangrene, caused by lower limb peripheral arterial disease (PAD). Critical threatening limb ischemia (CTLI) is the final stage of PAD, with macrovascular lesions caused by a decrease in distal perfusion. In 2020, approximately 2 million critical limb ischemia were diagnosed iin the 7MM countries (USA, Germany, UK, France, Italy, Canada, Spain). Among EU5 countries, Germany had the highest critical limb ischemia diagnosed prevalence. There is no effective treatment for Critical Threatening Limb Ischemia (CTLI: non-revascularizable critical limb ischemia, affects at approx. 5% of PAD).
Collategene (gene therapy with HGF plasmid) is the only approved critical limb ischemia Advanced Therapy treatment (Japan). Meanwhile, many cell therapies are being developed to target the population that is not appropriate for revascularization or has poor results following revascularization.
Advanced Therapy Medicinal Products represent a novel class of biological medicinal products because of its nature. One of the main differences between ATMP and conventional drugs is that ATMP are developed from living cells, engineered or not, recombinant acid nucleic, or the combination of those with a medical device of biomaterial, whereas most conventional drugs are synthesized molecules. Our group developed Phase II ATMP for CTLI using adiposederived allogeneic mesenchymal stromal cells expanded in conventional media (platelet lysate) (NOMA trial, NCT04466007, Coordinated by Profs D Garcia-Olmo and Bernat Soria, Source-AEMPS). In this project (COST-23) plan to use a New Xeno-free and Human component free culture media that we created (XANADU media, patent pending) which allows expansion to more than 25-fold with stable phenotype and genotype. This approach will reduce substantially the cost of production. Additionally intramuscular administration, as developed in the NOMA trial, reduces the hospital costs. All together we estimate a reduction by more than 60% the cost of the ATMP therapy for CTLI, then increasing the sustainability of the healthcare system (PERTE-Salud aims) and universalizing the treatment.
