Research Project
9525738
BioStrategies LC is developing the plant galactose-binding lectin, RTB, as an enzyme carrier capable of expanding delivery of enzyme replacement therapies (ERTs) to ?hard- to-treat? organs and tissues such as bone. The rare lysosomal disease mucopolysaccharidosis I (MPS I) is a progressive multisystem disorder, which presents with significant skeletal abnormalities that play a major role in patient disease progression. MPS I is caused by genetic deficiencies in the lysosomal enzyme ?-L- iduronidase (IDUA) which is critical for glycosaminoglycan degradation. Pathological accumulation of dermatan sulfate is particularly problematic in the musculoskeletal system leading to dysostosis, course facial features, short stature, arthropathy, and joint stiffness. Early-onset forms (Hurler syndrome) are typically treated by bone marrow transplantation and/or currently available ERT. However these treatments, alone or in combination, do not adequately correct or arrest skeletal disease progression. Preliminary studies indicate that our RTB-IDUA drug (IDUAL) may deliver the iduronidase lysosomal enzyme to bones of MPS I mouse model animals. The goal of this proposal is to demonstrate the feasibility of IDUAL to effectively treat the bone and connective tissues in the MPS I mouse. Specific Aims of this proposal are to 1) Assess the impacts of IDUAL treatment on early pathogenic events in MPS I animals during the bone growth phase, and 2) Evaluate molecular and morphometric readouts of MPS I skeletal pathologies during the bone remodeling phase following long-term treatment with IDUAL. Based on these proof-of-concept results, Phase II studies would support the scale-up manufacturing and rigorous preclinical assessments to move this promising product to an IND approval. The feasibility established here will also support extending the RTB carrier system to ERTs for other diseases having debilitating musculoskeletal involvement.
