Mapping the Effect of Excess Fatty Acids on Albumin-Drug Interactions by NMR

点击翻译按钮获取中文摘要

Therapure Biopharma Inc. (or Therapure in short) already developed a highly competitive product, referred tohere as "TBI-HSA", which is a therapeutic albumin designed for the cost-effective treatment of hypovolemiaand the control of oncotic pressure in surgical applications. Therapeutic albumin is also undergoing phase IIIclinical trials based on its potential use for treating dementia in Alzheimer's patients. The TBI-HSA biologicsis a viable alternative to traditional albumins obtained through Cohn's fractionation of pooled human plasmaand the prospect of future growth is excellent due to the rapidly aging population of Canada and the projectedincrease in demand for plasma biologics during surgeries. In order to fully exploit the full potential of thetechnology developed by Therapure for growth in these markets, it is essential to understand at the molecularlevel how the manufacturing process of TBI-HSA affects the active ingredient of this formulation, i.e. thealbumin protein. Here, we propose to determine through advanced Nuclear Magnetic Resonance (NMR)spectroscopy methods how a critical step of the TBI-HSA manufacturing process, the addition of stabilizers toenhance albumin stability, perturbs the interactions of albumin with common drugs, such as naproxen andwarfarin. Considering that alteration in these interactions affects the ability of albumin to function as abiotherapeutic, the molecular images provided by NMR will inform the future optimization of themanufacturing process implemented by Therapure. This type of optimization will provide Therapure a uniquecompetitive edge relative to its international competitors and thus will help Therapure significantly expand itsworldwide market. However, Therapure currently has no access to the specialized NMR expertise required togain this competitive edge. The Melacini group will provide the necessary expertise, as Dr. Melacinispecializes in the biophysical characterization of proteins by NMR. The application of these NMR imagingmethodologies to monitor how the TBI-HSA active ingredient changes during the manufacturing process willallow Therapure to further expand its share in the plasma biologics market.