A cartilage-targeted IGF-1-antibody fusion protein as a new therapeutic approach for IGF-1 deficiency.

Growth hormone (GH) insensitivity syndrome (GHIS) is a childhood growth disorder characterized by an inability to generate insulin-like growth factor-1 (IGF-1) in response to GH. Consequently, GH therapy is ineffective in patients with GHIS. Patients are often treated with recombinant IGF-1 instead, which requires twice-daily injections and is associated with adverse effects including hypoglycemia. In the current study, we evaluated CV1623-1, a cartilage-targeted antibody-like IGF-1 fusion protein as a potential new treatment for GHIS and for other disorders of linear growth involving IGF-1 deficiency. Using Ghrhrlit mice as a model for IGF-1 deficiency, we found that CV1623-1 stimulated the growth plate at a lower dose and decreased dose frequency compared with IGF-1. Alternate-day injections of CV1623-1 significantly increased body weight, tail length, and tibial bone length. In addition, CV1623-1, unlike IGF-1, did not induce hypoglycemia. Taken together, our findings indicate that CV1623-1 represents a promising new drug candidate for GHIS with improved efficacy, longer duration of action, and reduced hypoglycemia compared with the current treatment, recombinant IGF-1. Preclinical studies and clinical trials would be required to further validate the safety and efficacy of CV1623-1, paving the way for its potential clinical application as a new treatment for GHIS.