Conclusion of this study:
After following the module through the experiments do you feel the investigators were successful in accomplishing their goals?
The results of these studies show that rAAV-mediated gene transfer of the hFIX cDNA can correct or improve the bleeding problems associated with hemoplilia B mice. The significance of the canine studies was to view the results in a larger animal that would more closely simulate the results and dose requirements for humans. The investigators' results were promising. Treatment with the rAAV-cFIX into hepatocytes showed a 50-75% reduction in the whole blood clotting time in the two hemophilia B dogs. Furthermore, they site a marked decrease in spontaneous bleeding episodes in these dogs over an 8-month time period. The normal number of spontaneous bleeding episodes in hemophilia dogs is on average, 5 per year.
Can you think of some suggestions for further studies?
I might want to repeat the canine studies using a larger number of hemophilia B dogs, over a longer time period. A study of 2 dogs over an 8 month period is insufficient data when contemplating this as a potential treatment for humans with a Factor IX defiecency. Also I would want to experiment on the optimal dosage requirements to achieve higher levels of biologically active transduced hFIX. Could too high a dose cause any kind of problems? Could naturally occuring anti-AAV antibodies in the human population be a problem if using this vector and this technique? These are just a few questions that could be looked into if continuing this study.