Researchers have developed methods to endow large molecule vectors (such as adenovirus, retrovirus, liposomes, micelles, natural and synthetic polymers) and combinations of such vectors with the ability to target bone tissue in vivo with improved stability in the blood.
Gene and enzyme replacement therapy are promising treatments for bone related diseases. There are several diseases for which delivery of therapeutic agents to bone would be beneficial. For example,
Mucopolysaccharidosis IVA (MPS IVA) is an autosomalrecessive disorder caused by deficiency of acetylgalactosamine-6-sulfate-sulfatase (GALNS, EC 18.104.22.168) leading to accumulation of glycosaminoglycans
(GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Clinical manifestations vary from severe to an
attenuated form characterized by systemic skeletal dysplasia, laxity of joints, hearing loss, corneal clouding, and heart valvular disease, with normal intelligence. Generally MPS IVA patients do not survive beyond second or third decade of life, although patients with an attenuated form can survive into the seventh decade of life. Surgical interventions are used to treat some manifestations of the disease. Although other tissues are affected in MPS IVA patients, an idealtherapeutic agent would be efficiently distributed to bone and bone marrow. Mucopolysaccharidosis VII (MPS VII) patients would benefit greatly from the targeted delivery of β-glucuronidase (GUS). Another example is hypophosphotasia, for which the targeted delivery of tissue non-specific alkaline phosphatase (TNSALP) would be highly beneficial. However, there exists a need to facilitate the delivery of therapeutic agents, including polynucleotides and polypeptides, to bone.
The potential benefits of this technology include:
- Increase the affinity of therapeutic agents for bone
- Increase the effectiveness of enzyme replacement therapy
- Increase the number of treatments for various types of diseases that affect bone
This technology has potential application to various bone diseases including:
- Mucopolysaccharidosis (MPS) I, II, IV, VI, VII
- Paget’s disease of bone
- Osteogenesis Imperfecta (OI)
Researchers are seeking partners to further develop and commercialize this technology.