Optimized IGF-1 isoforms have been developed with improved potency in producing muscle hypertrophy.

Insulin-like growth factor I (IGF-I) is a key regulator of muscle development and growth. However, the complexity of IGF-1 activity is modulated by extensive alternative splicing and glycosylation. 

A former Penn researcher, Dr. Elisabeth Barton, generated new forms of recombinant IGF-I (rIGF-1). In contrast to the work that has focused on the independent actions of the C-terminal E-peptide of IGF-I, which have modest activity, require the IGF-I receptor, and can be detrimental to muscle strength, the new IGF-I forms include both the mature IGF-I protein and the E-peptide as a single protein. Further, the sites for glycosylation have also been eliminated, affording the production of a single and potent pro-IGF-I form.

The pro IGF-1 form is more potent and demonstrates enhanced IGF-1R activation both in vitro and in vivo. In recent in vivo experiments pro‐IGF‐I enhanced the immediate effect on muscle hypertrophy causing more than twice the increase in muscle mass than either mature IGF‐I or IGF‐IA at 1 week post‐injection. The increased potency means that lower protein levels are needed for the same benefit. In studies to determine the minimum effective dose, it was found that  a 3-fold lower level of pro-IGF-I production compared to mature IGF-I is sufficient to produce an equivalent hypertrophic response in muscle. 

• Increased potency of novel isoforms compared to current rIGF-1 or pegylated IGF-1
• Novel isoforms are more stable than current rIGF-1
• Potential for reduced dosing and reduction in side effects