Profiling the Development of Gene Therapies at Rejuvenate Bio

Here find a high-level look at the work of Rejuvenate Bio, a gene therapy company aiming to manipulating aging metabolism into a better shape. They have chosen to focus on the strategy of altering tissues to generate signal molecules known to be influential in the progression of aging. This is perhaps the easiest way forward for any gene therapy platform. Gene therapies are clearly the future, but at present it is somewhere between hard, expensive, and impossible to specifically target a gene therapy to most organs or cell types or tissues. If one can use one of the few established approaches, such as delivery of a gene therapy to the liver or injecting the vector directly into fat tissue, then one can turn cells into factories that manufacture and secrete the desired signal molecule. That signal molecule is then transported to the rest of the body.

While looking at previous lifespan and healthspan extension studies may seem an obvious place to start when seeking new gene therapies, the Rejuvenate Bio founders explain that there is more to it than just the results. “These studies are essentially long-term safety experiments where they showed durable safety, coupled with an ability to treat multiple different issues with the animal or at least prevent age related conditions. Our focus was on how to turn transgenic interventions into therapies that would be safe and relevant for human patients. That is where we started.”

The team studied those successful genetic interventions and how to “therapize” them – selecting the genetic or transgenic interventions that best lent themselves to becoming a gene therapy. In the end, the company arrived at three key longevity genes with proven efficacy and validated safety profiles, each associated with either an upward or downward trajectory through age: FGF21, which regulates important metabolic and immune pathways; TGFβ-1, which is a known driver of fibrosis and several cancers; and α-klotho, which is associated with cognitive performance as well as protection against heart and kidney diseases.

The Rejuvenate Bio founders explain how the company’s FGF21 gene therapy is delivered via a strain of adeno-associated virus that targets liver tissue. “Even if our FGF21 gene therapy is only infecting liver tissue, we can actually see systemic effects throughout the body. What we’re doing is turning the liver into a therapeutic bio factory, and then overexpressing this key signaling protein that then goes out through the blood stream and does its work across the body.” This approach has advantages over gene replacement therapies, as evidenced by the company’s recent success targeting arrhythmogenic cardiomyopathy in mice. “Because we’re utilizing a secreted protein for our delivery, we’ve shown that we’re able to hit large amounts of the cardiac tissue. Compare that to these groups who are trying to get the gene therapy to infect every cardiomyocyte that they’d like to change. That’s a key difference.”