Buckle up. High-stakes human testing has now begun on a gene therapy that promises to reverse aging at the cellular level. About four months after the U.S. Food and Drug Administration (FDA) gave Life Biosciences clearance to initiate its clinical trials, the Boston-based longevity startup announced on Tuesday that it’s just dosed its first patient.
Life Biosciences’s modest goal is to regenerate aging neurons in the optic nerves of patients struggling with glaucoma—a condition that often includes the irreversible death of neurons known as retinal ganglion cells, which connect the eye to the brain. The longevity firm’s strategy involves injecting a modified virus with tailor-engineered genes that reprogram cells to “reverse age-related epigenetic changes,” according to records with the U.S. National Center for Biotechnology Information.
But—while the FDA has cleared the company’s ER-100 drug for human tests—some researchers watching this space worry that these “reprogramming” therapies might lead to runaway (or exuberantly youthful) cellular growth, similar to past tests that may have caused cancer in mice.
“It’s gotten a lot of hype,” neurobiologist Pete Williams at the Centre for Eye Research Australia explained to the journal Nature. “If this goes catastrophically wrong, it might screw us all in the future.”
Fresh eyes
Life Biosciences focused on neurodegenerative diseases related to blindness, in part because the eye is a relatively isolated organ within the body where unintended consequences are less likely to get out of hand. To further increase its tests’ safety, the company’s ER-100 drug is only activated when patients simultaneously take the antibiotic doxycycline. Without it, the drug’s genes switch off.
“We’re going to give doxycycline systemically,” the company’s chief scientific officer Sharon Rosenzweig-Lipson told the nonprofit Lifespan Research Institute (LHI) this past February. The plan, she added, is to keep the genes activated over an eight-week period, more than the sporadic tests common in this field.
“We can achieve good reprogramming and good safety with a more continuous expression system,” Rosenzweig-Lipson said.
The core of the company’s treatment rests on breakthroughs by geneticist David Sinclair’s lab at Harvard Medical School, which showed that activating three specific genes could regenerate neurons and reverse vision loss in both aging mice and mice with glaucoma. Since then, Life Biosciences—which Sinclair co-founded—says it has optimized this approach via “comprehensive nonhuman primate studies.”
Still further beneath that foundational work, the company’s gene therapy drug builds off the Nobel Prize-winning discoveries of stem cell researcher Shinya Yamanaka, who first documented the genes that can reprogram adult cells to return to a stem cell-like state.
But, as you might imagine, it’s the very promise of these genes as a “factory reset” that can sometimes lead newly reprogrammed cells to veer off in the wrong direction. These “Yamanaka factor” genes, as LHI noted, have produced teratomas in earlier experiments, “bizarre tumors that are often found to contain hair, teeth, eyes, and other partially formed organs.”
The quest feel 10 years younger
As Karl Pfleger, an investor in a U.K. competitor to Life Biosciences, told MIT Technology Review this January, these early clinical trials are a long way from certain billionaire backers’ dreams of immortality. But it’s a start.
“The optimistic case is this solves some blindness for certain people and catalyzes [future] work,” Pfleger said. “It’s not like your doctor will be writing a prescription for a pill that will rejuvenate you.”
That said, Sinclair is already gunning to do just that, announcing plans to develop an oral version of his genetic “reprogramming” drugs as his bid to win a $101 million competition put on by the XPrize Foundation. The grand prize, ostensibly, will go to the team that can “restore” about 10 years to a patient’s life, making them a decade younger in under one year of treatment.
The contest will be something of a long shot. A recent attempt by one of Sinclair’s XPrize competitors last year created a toxic bloom of unwanted lipids in their test mice, “hindering the rejuvenation.”
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