First use of gene therapy to treat growth hormone resistant dwarfism in a mouse model.
Kian Chuan SiaShu Uin GanSiti Humairah Mohd RodhiZhen Ying FuJohn J KopchickMichael J WatersKok-Onn LeePublished in: Gene therapy (2022)
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 × 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.
Keyphrases
- gene therapy
- growth hormone
- binding protein
- body weight
- end stage renal disease
- multiple sclerosis
- type diabetes
- weight loss
- endothelial cells
- chronic kidney disease
- metabolic syndrome
- ejection fraction
- randomized controlled trial
- white matter
- adipose tissue
- peritoneal dialysis
- gene expression
- cell proliferation
- combination therapy
- cancer therapy
- genome wide
- ultrasound guided
- study protocol
- resting state
- patient reported outcomes
- pluripotent stem cells