Get ready. Human trials have kicked off for a gene therapy aimed at reversing cellular aging. Just four months after the FDA authorized Life Biosciences to start its clinical trials, the Boston-based startup has announced that it has treated its first patient.
The company’s goal is fairly straightforward: regenerate aging neurons in the optic nerves of patients dealing with glaucoma, a condition that often involves the irreversible death of retinal ganglion cells, which are essential for connecting the eye to the brain. Their method includes injecting a specially modified virus with genes designed to “reverse age-related epigenetic changes,” based on information from the U.S. National Center for Biotechnology Information.
However, some researchers are cautious, voicing concerns that these “reprogramming” therapies might lead to excessive cellular growth, potentially akin to past experiments that raised cancer risks in mice.
“There’s been a lot of buzz,” said neurobiologist Pete Williams from the Centre for Eye Research Australia, sharing his thoughts with Nature. “If this goes sideways, it could have serious implications for the future.”
New Perspectives
Life Biosciences is concentrating on neurodegenerative diseases linked to vision loss, partly because the eye is a relatively contained organ, reducing the risk of unintended outcomes. To enhance safety, their ER-100 drug only activates when patients take the antibiotic doxycycline simultaneously; otherwise, the genes are inactive.
“We’ll administer doxycycline systematically,” the company’s chief scientific officer, Sharon Rosenzweig-Lipson, mentioned to the nonprofit Lifespan Research Institute (LHI) earlier this year. She added that they aim to keep the genes switched on for eight weeks, rather than the typical sporadic testing seen in this field.
“We believe a continuous expression system will provide better reprogramming outcomes along with safety,” Rosenzweig-Lipson explained.
The treatment is built upon advancements from geneticist David Sinclair’s lab at Harvard Medical School, which demonstrated that activating three specific genes could regenerate neurons and potentially restore vision in aging or glaucoma-afflicted mice. Life Biosciences, co-founded by Sinclair, claims to have optimized this approach through extensive studies on nonhuman primates.
At the foundation of this gene therapy are the Nobel Prize-winning discoveries by stem cell researcher Shinya Yamanaka, who identified the genes capable of reprogramming adult cells back to a stem cell-like state.
Yet, this idea of a genetic “factory reset” is not without risks. As noted by LHI, these “Yamanaka factor” genes have previously resulted in teratomas in some experiments, leading to bizarre tumors containing hair, teeth, and other partially developed organs.
Aiming to Feel Younger
As investor Karl Pfleger from a U.K. competitor to Life Biosciences pointed out to MIT Technology Review this January, these initial trials are just a step towards the lofty dreams of billionaire investors in the quest for immortality. It’s promising, but there’s a long way to go.
“In an ideal scenario, this could alleviate some vision loss for select individuals and inspire future research,” Pfleger noted. “But don’t expect to walk into a doctor’s office asking for a rejuvenation pill.”
That said, Sinclair has already begun pursuing that very goal, revealing intentions to develop an oral version of his genetic “reprogramming” treatments as part of his entry into a $101 million competition organized by the XPrize Foundation. The objective? To “restore” about 10 years to a patient’s life within a year of treatment.
This contest, however, could be quite challenging. A recent attempt by one of Sinclair’s competitors resulted in toxic lipid overproduction in test mice, undermining their rejuvenation efforts.
