New design method stabilizes human growth factor for potential therapeutic use

A recent study published in the Biophysical Journal introduces a novel method for stabilizing human fibroblast growth factor (FGF), a molecule with significant wound-healing and antidiabetic properties. FGF plays a crucial role in cell proliferation and differentiation, essential processes for life, as explained by Suresh Kumar Thallapuranam, the corresponding author and a University Professor of chemistry and biochemistry at the University of Alberta.

FGF, while vital for cell growth and tissue repair, has a limited half-life in the body, rendering it unstable and short-lived. This short stability period poses a challenge for its therapeutic potential. However, the research team at the University of Alberta has found a way to enhance FGF's structural stability and cell proliferative activity, potentially overcoming this limitation.

Thallapuranam and his collaborators achieved this by identifying a specific region in FGF known as the heparin-binding pocket. By introducing a mutation, named R126E, into this pocket, they were able to reverse the charges that typically bind FGF to heparin. This charge-reversal mutation resulted in a more stable FGF structure, which could be beneficial for therapeutic applications.

The researchers employed advanced multidimensional nuclear magnetic resonance spectroscopy to uncover the three-dimensional structure of FGF and decipher the mechanism by which it interacts with heparin. This intricate process took more than a decade to complete, highlighting the complexity of the research involved.

The patent-protected charge-reversal mutation has opened up new possibilities for developing a "super FGF" with enhanced metabolic properties. This "super FGF" could potentially aid in improving cellular oxidation of fatty acids and glucose, as well as clearing cholesterol, which would be advantageous in the treatment of obesity and related metabolic diseases.

While the current study focuses on the enhanced stability and activity of FGF, further research is needed to evaluate the safety and efficacy of this modified factor for therapeutic use. The development of a stable, biologically active version of FGF could potentially revolutionize tissue repair processes, particularly in metabolic diseases such as chronic diabetes, which often lead to severe complications like infections and amputations.