Industrial development of pulmonary surfactant from animal sources

• Grant number: 05/60543-1
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - SUS (PITE-SUS)
• Start date: May 01, 2006
• End date: April 30, 2009
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Agreement: CNPq - PPSUS
• Principal Investigator: Isaias Raw
• Grantee: Isaias Raw
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• City: São Paulo
• Partner institutions: Ministério da Saúde (Brasil). Sistema Único de Saúde (SUS)

Abstract

Surfactant deficiency at birth, caused by premature delivery, is responsible for the development of neonatal respiratory-distress syndrome (RDS). RDS affects 50% of the neonates with gestational age between 26 and 28 weeks and 20 and 30% of neonates with 30 and 31 weeks. Since 90's, surfactant replacement therapy is the common clinical conduct. Due to its nature complexity exogenous pulmonary surfactant production is considered a hard and an expensive process, which results in a high cost (R$ 700,00 for the usual clinical dosage of 100 mg surfactant.kg-1 body weight). In this scenario, the Butantan Surfactant Project of a new surfactant formulation with a low cost (around 35% of the total cost of the imported available formulation) was an important challenge for the future of the surfactant replacement therapy at developing countries like Brazil. The developed technology (PI 9900436-4) generated a surfactant formulation that is being tested all over Brazil maternities (33 hospitals from Maranhão to Rio Grande do Sul) since April 2005. The clinical trial is supposed to be finished at December 2006. The surfactant production to attend this demand was done at the pilot plant supported by F APESP (97/11650-1) and Fundação Butantan. This new proposal is to apply for funds to develop and to set up the industrial process of surfactant production and to continue to study some preparation improvements through addition of its collectins or antioxidant proteins, increasing surfactant resistance to inactivation and consequently dose-efficiency would be contemplated. Therefore, we proposed new surfactant generations that will be available in 4 or 5 years showing new compositions like basic surfactant added with Surfactant protein A (SP-A). SP-A belongs to the collectin class of C-type lectins similar to C1q. These proteins are also called defense collectins, and they play important roles in innate immunity. Substantial evidence indicates that SP-A is involved in innate host defense and inflammatory processes of the lung, as well as in several aspects of pulmonary surfactant biology. To isolate and purify SP-A at an industrial scale improving some protocols previously obtained (F APESP 00/01104-4) is also an objective of this proposal. Pure isolated SP-A is also an important goal for future applications itself as a hormone that signals the initiation of parturition. We are also studying new uses of pulmonary surfactant therapy and surfactant formulations (to add antioxidant enzymes) for treatment of adults with acute respiratory distress syndrome (ARDS) in collaboration with lung disease specialists that before our low cost formulation have enormous difficulties to realize such tests. The search for protease inhibitors obtained from pulmonary extract as by-products of the main production is also an objective of this proposal wondering that proteolytic damage may occur in acute or chronic inflammation where high numbers of neutrophils are attracted into the lung and the amount of neutrophil elastase released overwhelms antiprotease defenses. The pulmonary surfactant production is the beginning of a line of non immune biological products developed by Instituto Butantan that includes blood derivatives, hormones and alpha-interferon. To develop all these products is important to mention that it is a result of research activities of 25 doctors from the Centro de Biotecnologia, in addition to masters and post-graduate students besides the Divisão Bio-Industrial (300 researchers and technicians being 50% employed by Fundação Butantan) plus private partners and/or researchers from the universities. (AU)