Lysosomal storage disorders (LSDs), such as Fabry, Gaucher, Hunter, and Sanfilippo diseases are a group of rare diseases that currently lack a definitive cure. LSDs individually occur with incidences of less than 1:100,000; but as a group, the incidence is about 1:5,000 - 1:10,000, representing a serious global health problem. Therefore, development of new treatments for this type of rare diseases has become a key priority for European Research policy.
For instance, the lack of α-galactosidase A (GLA) activity in Fabry disease (FD) patients causes the accumulation of glycosphingolipids (such as Gb3) in the vasculature leading to multiple organ pathology, and the death of patients before 45 years old. Enzyme replacement therapy (ERT), which is the most common treatment of LSDs, exhibits several drawbacks: short plasma half-life (high uptake of the GLA by the liver and high degradation rate), poor biodistribution, high immunogenicity, and low capability to cross biological barriers such as the blood brain barrier (BBB). In this scenario, an appropriate nanoformulation of the GLA enzyme is foreseen as a critical step to improve the ERT.
In the frame of Smart-4-Fabry EU project (#720942), a new GLA nanoformulation (nano-GLA) more effective than current treatment for FD patients has been obtained. The Committee for Orphan Medicinal Products (COMP) recommended the designation of this new medicinal as an orphan medicinal product for the treatment of Fabry disease. Upon this recommendation, the new medicinal nanoformulation was included in the Community Register of orphan medicinal products
Such gain in the efficacy would further allow lowering the clinical dose and spacing the administration schedule for FD patients (currently being administered every other week). The final benefit will be seen as a considerable reduction on the FD treatment cost and a substantial improvement in the quality of life for FD patients.
The Smart-4-Fabry project has lasted 48 months and has contemplated the necessary activities to advance the innovative nano-GLA from a solid experimental Proof of Concept (TRL3) to the regulatory preclinical phase (TRL5-6). The one-step & green, DELOS platform based on the use of compressed CO2 has been used for the manufacturing of this novel nanoformulation with high quality.
Several research groups with experience in nanomedicine, molecular self-assembling and preclinical testing (CIBER-BBN/Spain, Aarhus University/Denmark, Technion/Israel- and Joanneum Research/Austria), together with a recognized company in the field of regulatory preclinical testing (Covance Laboratories/UK), a nanomedicine early adopter pharmaceutical company (Biokeralty/Spain), a SME specialized on
Pharmaceutical development & technology transfer of the DELOS nanoformulation platform (Nanomol Technologies/ Spain), a SME for the development& production of enzymes (LEANBIO/Spain), a recognized CRO in developmental processes of biological products, experts on industrial nanosafety (BioNanoNet/ Austria) and drug regulation (DDR/ Spain), have joined efforts to advance the new nanomedicine for Fabry disease treatment to an advanced stage of preclinical development.
