Proof-of-concept study targets 4 diseases in mice
In a study done by famous George Church’s lab, scientists demonstrated the use of genetic engineering in disease prevention. They improved various psychological and biochemical measures in murine models of popular human diseases. Experiments can be seen more as a proof-of-concept than preclinical research, because of discrepancy between those models and human diseases.
Gene therapies relied on adeno-associated viruses (AAV8) containing genes TGFβR2, FGF21, αKlotho. They aimed to infect the liver, which will then secrete the proteins into bloodstream. After interventions, changes in circulatory concentration were confirmed for all targets. Combined therapy of TGFβR2 + FGF21 addressed all four models. The third gene – αKlotho – negatively interacted with FGF21.
FGF21 was hoped to modify metabolism and alleviate obesity and type II diabetes, whereas αKlotho and TGFβR2 were expected to lower the risk of unilateral ureteral obstruction (kidney failure) and ascending aortic constriction (heart failure).
G. Church concluded:
Achieving these results in non-transgenic mice is a major step toward being able to develop this treatment into a therapy, and co-administering multiple disease-addressing genes could help alleviate the immune issues that could arise from the alternative of delivering multiple, separate gene therapies for each disease.
Publication: Noah Davidsohn, Matthew Pezzone, Andyna Vernet, Amanda Graveline, Daniel Oliver, Shimyn Slomovic, Sukanya Punthambaker, Xiaoming Sun, Ronglih Liao, Joseph V. Bonventre, George M. Church (2019). A single combination gene therapy treats multiple age-related diseases. doi:10.1073/pnas.1910073116