“We are very excited to translate our winning gene therapy work from mice to dogs, where there is a dearth of treatment options to combat age-related diseases,” said Daniel Oliver, CEO and co-founder of Rejuvenate Bio, who was formerly an Entrepreneur-in-Residence at the Wyss Institute and a Blavatnik Fellow at Harvard Business School, and is a co-author of the PNAS publication.
Funding was secured from the Department of Defense’s Small Business Innovation Research Program, as well as funding from other investors and a grant from the American Cavalier King Charles Spaniel Club; with this support Rejuvenate Bio is launching a pilot study to test efficacy in halting mitral valve disease which affects the majority of these Spaniels by the age of 8 to cause heart failure. Treatment is hoped to be expanded to include all dog breeds following demonstration of efficacy; more than 7 million dogs suffer from mitral valve disease in America alone.
“We are very passionate about and focused on dogs’ health, because so many dog owners around the world have to helplessly watch their beloved pets’ quality of life deteriorate as they age,” said co-author Noah Davidsohn, Ph.D., who is a co-founder and Chief Technology Officer of Rejuvenate Bio and a former Research Scientist at the Wyss Institute and HMS. “We want to get rid of the morbidities associated with aging, so dogs can be as happy and healthy as possible throughout their lives.”
Providing a combination gene therapy of three longevity associated genes to mice was hypothesized to combat age related disease to confer health benefits. FGF21, sTGF𝝱R2, and 𝛂Klotho genes were previously shown to promote increased health and lifespan benefits in mice genetically engineered to overexpress them; the goal was to produce the same outcome in non-engineered animals. Separate gene therapy delivery vehicles were created for each gene using a serotype of AAV8 which were then injected into mouse models of type 2 diabetes, obesity, heart failure, and renal failure to examine for beneficial effects.
A single gene therapy administration of FGF21 alone caused full reversal of type 2 diabetes and weight gain in obese diabetic mice; and combination with sTGF𝝱R2 reduced kidney atrophy by 75% in animals with renal fibrosis. sTGF𝝱R2 alone and in combination with either of the other 2 gene therapies improved heart function in animals with heart failure, demonstrating that combination of FGF21 and sTGF𝝱R2 gene therapies could treat all four age related conditions successfully to improve health and survival. It was noted that the injected genes remained separate from the animal’s genomes, did not modify their natural DNA, and can’t be passed onto future generations or between living animals.
“Since the treatment works to suppress fibrotic processes, we believe it could also be applied to other heart diseases such as dilated cardiomyopathy, which eventually leads to congestive heart failure and/or sudden death in affected dogs,” said Davidsohn. “We are hopeful that our pilot study will allow us to move toward an animal drug trial with the FDA, which generally takes about three years to complete.”
“Science hasn’t yet found a way to make complex animals like dogs live forever, so the next best thing we can do is find a way to maintain health for as long as possible during the aging process,” said Rejuvenate Bio co-founder George Church, Ph.D, who is also the Robert Winthrop Professor of Genetics in the Blavatnik Institute at HMS and a Core Faculty member of the Wyss Institute.
“The Wyss Institute is extremely proud of the Rejuvenate team for reaching this milestone on the path to commercialization of a truly novel technology, and we are excited to follow the rest of their journey from the lab to the clinic,” said Donald Ingber, M.D., Ph.D., who is the Wyss Institute’s Founding Director as well as the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
