A child's growth is dependent on the proper functioning of the growth plate, a specialized cartilage structure located at the ends of long bones and within the vertebrae. The primary function of the growth plate is to generate new cartilage, which is then converted into bone tissue and results in the lengthening of bones. Failure of the growth plate to function properly can result in short stature or sometimes a skeletal dysplasia, such as achondroplasia, in which the bones are not just short but also malformed. Current treatments for severe short stature and skeletal growth disorders are limited. Recombinant human growth hormone (GH) is typically used, but the results are often less than optimal and growth hormone has potential adverse effects.

Researchers at the Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD) Section on Growth and Development, collaborating with the NCI Laboratory of Experimental Immunology, created human monoclonal antibody fragments that bind to matrilin-3, a protein specifically expressed in cartilage tissue. When injected intravenously in mice, these antibody fragments honed to cartilage and were not detectable in other tissues. Coupling these cartilage-binding antibodies to growth-stimulating endocrine factors, such as growth hormone and IGF-I, and paracrine factors, such as CNP, could allow therapy targeted specifically to growth plate, and also articular cartilage, thereby opening up broad new pharmacological approaches to treat skeletal dysplasias and short stature. The same approach could also be used in adults to treat articular cartilage diseases like osteoarthritis. The research is currently in preclinical development, with in vitro data and in vivo mouse model data demonstrating that these antibody fragments target cartilage in vivo.

The researchers are interested in licensing this technology or for a collaboration to explore applications of this new approach. For example, a collaborator could produce fusion proteins combining the antibody fragments with various chondrogenic proteins that enhance growth. The collaborator might produce and purify the fusion proteins, which could then be tested for therapeutic effects in mice by the NICHD investigators.

Competitive Advantages:

• Avoidance of the risks associated with systemic treatment using growth hormone, such as increased intracranial pressure, slipped capital femoral epiphysis, insulin resistance, and possibly type II diabetes

Commercial Applications:

• A new treatment option for cartilage disorders, such as (1) skeletal dysplasias, (2) short stature, and (3) articular diseases like osteoarthritis