IGF-1-BP3

SomatoKine or IGF-1-BP3 is being developed by Insmed (formerly Celtrix Pharmaceuticals). SomatoKine is a recombinant fusion of insulin growth factor-1 (IGF-1) complexed to its major binding protein BP-3,which mimics the biological effects of IGF-1. SomatoKine acts as an insulin sensitizer and as an anabolic agent. The administration of IGF-1 as a fusion protein appears to avoid many of the side effects seen when it is administered directly, and an additional benefit is its longer half-life.

The clinical use of IGF-1-BP3 has been explored for four different indications: growth hormone insensitivity syndrome (GHIS), diabetes, osteoporosis and severe burns, although it is now only in active development for the treatment of GHIS and diabetes. Its development for the treatment of osteoporosis and severe burns has been postponed.

Muscle atrophy and wasting is a serious problem that occurs in patients with prolonged debilitating illness, burn injury, spinal injury, as well as with space flight. Current treatment for such atrophy, which often relies on nutritional supplementation and physical therapy, is of limited value in preventing the muscle wasting that occurs. Considerable recent attention has focused on the use of anabolic growth factors such as insulin-like growth factor (IGF-1) in preventing muscle atrophy during limb disuse or with various catabolic conditions. However, potential side effects such as hypoglycemia appear to be limiting factors in the usefulness of IGF-1 for clinical treatment of muscle wasting conditions. The formulation of IGF-1 used in this study – IGF-1-BP3 –  is already bound to its endogenous-binding protein (BP3) and, as a result, has a greater specificity of action and significantly less hypoglycemic effect. Using a rat model of hind limb suspension (HLS) for 10 days, we induced marked muscle atrophy that was accompanied by enhanced muscle proteolysis and reduced muscle protein content. When HLS rats were treated with IGF-1-BP3 (50 mg/kg, b.i.d.), they retained greater body and muscle mass. Muscle protein degradation was significantly reduced and muscle protein content was preserved. The rate of protein synthesis, although somewhat reduced in HLS muscle, was not significantly elevated by IGF-1-BP3 treatment. Volume density of HLS-treated muscles were increased compared to untreated HLS rats and the actual number of fibers per area of muscle was likewise increased. The results of the current study suggest that IGF-1-BP3 might be useful for inhibiting muscle proteolysis in catabolic conditions and thus preserving muscle protein content and mass.