This document discusses using microgravity exposure aboard the International Space Station to develop new therapeutics for infectious diseases. An academic-industry partnership sends experiments to study how microbes like Salmonella and other pathogens change in space, which may uncover new drug targets. They use a small worm called C. elegans that eats and reports on bacterial virulence. Spaceflight studies have identified virulence genes and informed vaccine development strategies. Findings from microbes like MRSA could yield new therapies to treat diseases on Earth. Using the unique environment of space may speed up the drug development process.

1. ISS National Laboratory Pathfinder Missions Therapeutics for Infectious Disease Jeanne L. Becker, Ph.D.

2. Overview: Therapeutics for Infectious Disease Academic – Industry partnership Uses microgravity exposure to uncover new targets for treatment against microbes ISS National Laboratory Pathfinder Vaccine (NLP-V) Missions Validates the utilization of space for commercial development NASA provides flight opportunities to accomplish commercial development goals

3. Partners Academic : Durham VA Medical Center Duke University Max Planck Institute for Infection Biology Hardware Provider : BioServe Space Technologies Industry : Astrotech / Astrogenetix

4. Why space? Effect : Growth within the space environment induces changes in microbial cells. Result : These changes are may be associated with: Growth Antibiotic resistance Pathogenicity Virulence Strategy : Take advantage of new knowledge uncovered by exposure to microgravity to treat infectious disease.

5. An experiment conducted on the space shuttle demonstrated that Salmonella grown in space becomes more virulent, as compared to the same bacteria grown here on earth

6. A good vaccine must be: Strong enough to induce an adequate immune response Strong enough to provide protection from future Salmonella exposure Weak enough to allow administration with little or no risk of illness If the cause of the increased virulence could be determined, can this knowledge be used to create a vaccine?

7. Scientific Approach Leveraged ground-based work to identifying genes as candidate virulence factors Leveraged ground-based assays to optimize host-microbe interactions Leveraged existing flight experimental hardware Developed an in-flight virulence assay

8. Model organism used is Caenorhabditis elegans , a small (1 mm long) soil nematode Eats bacteria, such as Salmonella Reports bacterial virulence (ability to cause disease )

9. Bacteria and worms launched Brought together in space If bacteria remain virulent, worms are killed, bacteria grow If bacteria lose virulence, they are eliminated via ingestion by worms Created strains of genetically altered bacteria

10. Flight Studies STS-123, 124, 126: Enhanced Salmonella virulence Gene target identification Vaccine development strategy STS-119, 125: Survey flight for virulence New organisms Use of Salmonella as positive control Taking advantage of the changes in biological processes that occur in microgravity to create new treatments for disease

11. Microbes flown: Methicillin resistant Staphylococcus aureus (MRSA) Listeria monocytogenes Pseudomonas aeruginosa Klebsiella pneumoniae Streptococcus pneumoniae Proteus mirabilis Enterococcus faecalis Candida albicans Current focus: MRSA

12. Findings made in space are the product of fundamental research. The science has facilitated development of a privately held venture. Eight successful spaceflight payloads have been conducted ~ two years with industry support. Initial work focused on analysis and definition of virulence targets for Salmonella . Work with additional microbes is ongoing, with a current focus on MRSA. Pathfinder Progress

13. How can using space change drug development on earth? The R&D pipeline for a single agent may take years of work to allow identification of good candidates for pharmaceutical applications. At the end of this period, the possibility exists that the candidate agent is not suitable for continued development. The resources expended getting to this point could be potentially minimized by using a process which identifies promising agents/drug candidates earlier in the development pipeline and allows for quicker testing to evaluate downstream efficacy and market potential. Using space, years could be eliminated from R&D pipeline activities, to allow fast-tracking of promising agents and termination of unsuccessful agents at earlier time points .

14. Using Space to Develop Products for Earth Commercial vaccine New therapies + = Virulence Gene Deletion Flight testing IND

15. John Phillips working with the experiment. The canister houses 8 individual test tubes, each containing replicates of the different organisms. http:// www.youtube.com/watch?v =n57djMwDZAs