The current inability to effectively deliver corrective doses of lysosomal
enzymes to key cells involved in cardiovascular and cerebrovascular disease
remains a significant hurdle for rare lysosomal disorders (LSD) such as Fabry
disease and other diseases with significant cardiovascular pathologies.
BioStrategies LC is developing the plant lectin RTB as a carrier capable of
expanding enzyme delivery to “hard-to-treat” organs and tissues including heart,
brain, and bone. Lectin mediated ERT delivery has recently shown promise in
other LSDs including MPS I and GM1. This SBIR is focused on developing a
“delivery-enhanced” enzyme replacement therapy (ERT) for patients with Fabry
disease. Fabry is a X-linked LSD caused by genetic deficiencies in alpha-
galactosidase A (a-GalA) leading to severe multi-organ pathologies with cardiac
death, followed by stroke, as the leading causes of death. Fabry disease has
emerged as the key LSD model for heart disease due to extensive
cardiomyopathy and other cardiovascular presentations.
Our long-term goal is to bring an ERT capable of treating the full spectrum of
progressive cardiac and other disease manifestations to Fabry patients.
Objectives of this Phase I SBIR feasibility study are to produce bioactive a-
GalA:RTB fusions and demonstrate product delivery into human myocytes,
correction of lysosomal phenotype in Fabry cells, and biodistribution to heart and
other tissues in the Fabry mouse model. Success in Phase I feasibility goals will
support moving on to rigorous Phase II SBIR follow-up preclinical assessments
aimed at moving this promising ERT product to an IND. The feasibility
established here will also support expanding the RTB carrier system to other
ERTs and therapeutics for diseases having life-threatening cardiovascular