George Church: Learn from COVID and fast-track therapies that reverse aging

Top aging scientist says that many more people die from aging than in pandemics, and the benefits of reversing aging are too beneficial for governments to ignore.

All eyes are on the Emerald Isle this week as the Longevity Summit Dublin brings together a host of speakers covering the spectrum of this booming sector. Delegates have been hearing from some of the leading entrepreneurs, companies, investors, and researchers in the field as they address many of the hot-button topics affecting longevity. One of those speakers is the so-called “father of genomics” – Harvard professor of genetics, George Church – who closes the conference later today with a keynote on Gene, cell and organ therapies for de-aging.

Longevity.Technology: In addition to his Harvard professorship, Church heads up synthetic biology at the Wyss Institute, where he oversees development of new tools with applications in regenerative medicine. Much of his focus more recently has been on the development of gene therapies targeting age-related disease, a passion that led him to co-found Rejuvenate Bio, with the goal of creating “full age reversal gene therapies.” We caught up with Church ahead of his Dublin presentation for a brief conversation on longevity.

Dr Church’s name is synonymous with genomic science, and he was a key contributor to the Human Genome Project and technologies including next-generation fluorescent and nanopore sequencing, aimed at understanding genetic contributions to human disease. However, he doesn’t feel that those initiatives did a huge amount to move the aging field forward.

All eyes will are on the Emerald Isle this week as the Longevity Summit Dublin brings together a host of speakers covering the spectrum of this booming sector
Harvard professor of genetics, George Church, in the lab.

“They have provided aging researchers with useful reference points to go back and check their work, but the key advances in aging have really been made through the fundamental research on key pathways and drivers of aging,” says Church. “However, what we can take from those projects was their contribution towards technology improvements that have reduced the cost of DNA sequencing from three billion dollars in 2004 to just three hundred dollars today.”

Gene therapies for aging a win-win

Thanks to technological advances, it was estimated that mapping a human genome cost an estimated $20–25 million in 2006, although this was using haploid sequencing unsuitable for phenotype prediction. Skip ahead to today, and start-up Nebula Genomics (a company founded by Church) now offers diploid whole genome sequencing for as little as $300 – a remarkable achievement by any standard. (Learn about the differences between haploid and diploid sequencing here.)

Alongside other technical developments, this kind of cost reduction will, Church believes, contribute to making gene therapies viable for everyone to benefit from, not just the wealthy. Public perception of gene therapy has taken a bashing recently thanks to drugs like Zynteglo, which was branded “the most expensive medicine in history” at $2.8 million per dose earlier this year. But Church doesn’t see the same issue being a factor when it comes to future therapies against aging.

“Those expensive gene therapies are for rare diseases, and their pricing reflects of the ratio of R&D costs to number of patients,” says Church. “But aging and its associated diseases affect nearly everyone. When you consider the volume of people that will be able to benefit from an age-reversing therapy, combined with the potentially huge benefits to society that such a treatment would enable, then it is a win-win for governments, healthcare providers and developers alike.”

Lessons from COVID pandemic

Under current conditions, gene therapies for aging and age-related diseases are likely to take 10 years to get approved, but Church points to how the world acted to fast-track approvals for COVID-19 vaccines in just one year.

“The top five vaccines were formulated as gene therapies, and showed how quickly and safely we can move when there are extenuating circumstances,” he says. “Well, I would say that many more people are dying and in poor health as a result of the effects of aging, so perhaps aging should also be considered an extenuating circumstance.”

In addition, Church points out, the cost of the vaccines was around $2 to $20 per dose – a figure that healthcare systems around the world could manage if a gene therapy for aging were similarly priced. 

So how close are we to seeing an approved gene therapy for aging? Pretty close, thinks Church, while admitting he’s biased because of the work going on at Rejuvenate Bio. He co-founded the company in 2019 with his former postdoctoral fellow Noah Davidsohn, with the goal of “eliminating aging and age-related diseases and increasing healthspan.”

Combine therapies for multiple diseases

Church believes that gene therapies hold greater promise for age reversal than small molecules, because they might avoid frequent dosing and be more target-specific, while hitting all ten key pathways in one go, so it’s perhaps no surprise that Rejuvenate Bio is working on therapies that could tackle several age-related conditions at once.

“We have already published on work conducted in mice, which showed that four age-related diseases (obesity, type II diabetes, heart failure, and renal failure) can be treated simultaneously with a single combination gene therapy,” says Church. “And we’ve gone on to show we can do it with five diseases as well.”

But Rejuvenate Bio isn’t stopping at mice. The company also has a significant animal health pipeline, which is already engaged in the development and commercialisation of a gene therapy for Mitral Valve Disease (MVD) in dogs.

Alongside other technical developments, this kind of cost reduction will, Church believes, contribute to making gene therapies viable for everyone to benefit from, not just the wealthy.
Noah Davidsohn, Church’s co-founder at Rejuvenate Bio, with his German Shepherd “Bear”.

“Our animal health pipeline also gives us a unique advantage in that the results directly inform the direction of our work in our human therapies, and I believe this will allow us to deliver results faster.”

The company’s lead therapy (RJB-01) targets the FGF21 and sTGFβR2 genes, and it is hoped it will deliver cardiovascular, metabolic and renal benefits. Following results from the trial in dogs, it is expected that RJB-01 will move into IND-enabling studies ahead of Phase 1 clinical trials – likely next year.

Church is also enthusiastic about the recent uptick in investment and the growing interest in the longevity field.

“It’s clearly a good thing – not only because it helps drive the field forward, but it also validates a lot of the great work that has been done in academia over the years,” he says. “Not that long ago, people were avoiding the field because of the sketchy image it had. Now we are attracting young, talented scientists, which is what we need to keep progressing.”

Photos: Church Laboratories, Harvard University.
Main image: “Out of the box” by artist/scientist, Joe Davis