Matt Gethers/20.380 HIV Project/Technical Paper/Jessie InVivo

Jessie: In Vivo and Clinical Studies

Introduction/Definitions

• Purpose of In Vivo Studies/Animal Models
• Purpose of Pre-clinical studies
• Brief history of clinical trials

Proof of Concept - In Vivo Studies

• Animal Model: Most likely macaque
  • Can use pig-tailed macaque with the stHIV that has a 95% similarity to HIV-1, but infection only lasts a couple months and does not progress to AIDS
    • Can be used to test prophylactic effect
  • Can use macaque model with SIVmac that will allow macaque to develop SAIDS
    • Are SIV and HIV similar enough for this to be a proof of concept?
• Things to look at:
  • Varying doses of HSCs - what is the optimal/plausible number of engineered HSCs needed?

Pre-clinical Studies

• Biggest concern is safety
• Can engineered HSCs become cancerous? - Drug super-sensitivity will be helpful
• What other safety concerns are there with regards to stem cell therapies?
• Need to prove natural functionality of engineered HSCs
  • Differentiate properly
  • RBCs function properly
• What else do we need to prove before getting FDA approval?

Clinical Studies

• Phase I
  • Prove mainly safety of treatment in humans
  • Should we do similar to Koronis and divide into Ia and Ib where Ia is in healthy volunteers and Ib is in people who have failed other HIV treatments?
  • Where should we conduct our trial? US or Africa?
• Phase II
• Phase III