First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model

The only treatment tested for growth hormone receptor (GHR) defective Laron Syndrome (LS) is injections of recombinant insulin-like-growth factor 1 (rhIGF1). The response is suboptimal and associated with progressive obesity. In this study, we treated 4-5-week-old Laron dwarf mice (GHR-/-) with an adeno-associated virus expressing murine GHR (AAV-GHR) injection at a dose of 4 x 10(10) vector genome per mouse. Serum growth hormone (GH) levels decreased, and GH-responsive IGF1, IGF binding protein 3 (IGFBP3) and acid labile subunit (ALS) increased. There was a significant but limited increase in body weight and length, similar to the response to rhIGF1 treatment in LS patients. All the major organs increased in weight except the brain. Our study is the first to use gene therapy to treat GH-receptor deficiency. We propose that gene therapy with AAV-GHR may eventually be useful for the treatment of human LS.

Automated summary

This study is the first to use gene therapy to treat GH-receptor deficiency. By injecting AAV-GHR, the serum GH levels decrease and the levels of GH-responsive IGF1, IGFBP3, and ALS increase in mice. It also causes a limited increase in body weight and length, similar to the response to rhIGF1 treatment in LS patients. This study is of great importance for the development of gene therapy for human LS treatment.