Biophysical Characterization and Preformulation Studies of Human Mesencephalic Astrocyte-Derived Neurotropic Factor.

A novel neurotrophic factor, human mesencephalic astrocyte-derived neurotrophic factor (hMANF), is being considered a therapeutic agent for a variety of diseases. However, little, if anything, has been reported about its stability. A preformulation study was conducted to assess the stability of hMANF as a function of pH and temperature. In addition, the effects of buffers and other excipients were evaluated as well. While the chemical and physical stability of hMANF decreases near pH 4, overall, the protein appears to be quite stable, especially near pH 6. Both histidine and phosphate appear to be suitable buffers in this pH range. Some loss of stability was noted above pH 6.5 as well. The stability profile of hMANF was comparable at 1 and 10 mg/mL. The decreased stability at acidic pH is correlated with the loss of the native α-helical conformation, as shown by FTIR spectroscopy. These studies indicate that hMANF is quite stable near pH 6, and formulations capable of exhibiting adequate long-term stability in aqueous solutions should be possible.