Plasma fractionation unused intermediates proteome as a potential source of new therapies for ultra-rare diseases

Human plasma, with its complex proteome, is a valuable source for developing therapeutics to address rare diseases caused by protein deficiencies1. Despite the complexity, only around 20 plasma protein therapeutics are utilized for treating life-threatening conditions [1]. Current plasma fractionation processes generate significant unused intermediates, providing an opportunity for novel therapy development. At Kedrion’s manufacturing sites (Bolognana, IT; Melville, US; Godollo, HU; Elstree, UK), diverse unused intermediates are generated, recently characterized in the case of the Bolognana plant [2]. This project aims to map their protein content for discovering therapies for rare diseases without diverting plasma from other manufacturing processes. In particular the main purpose is to detect and characterize a specific protein among unused intermediates, namely plasminogen (PLG) which plays a crucial role in fibrinolysis, wound healing, and other processes [3]. Main PLG indication is related to protein Type I deficiency, for which a therapy (derived from whole plasma) is already available. The use of waste fractionation intermediates could expand its availability for alternative conditions, such as diabetic wounds and burns3. To achieve this goal, the following workflow is being carried out: proteomic analysis on unused intermediates to map PLG presence, followed by validation by western blot and antigen determination techniques. Selection of the proper intermediate and solubilization conditions, including buffer and pH, will be then based on PLG characterization in terms of antigen level, protein fragmentation pattern, and functionality by chromogenic assay. This will be the initial step for the development of a new PLG experimental prototype from unused fractions. References: [1]. Strengers PF (2023) Transfus Med Hemother, 50(2):p. 116–122. [2]. Zanardi A, Nardini I et al (2024) Commun Biol.; 7(1):140. [3]. Al Kayal T et al (2022) Pharmaceutics 14(2):251.