World-first: therapy to make cells young again trialled in a person
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World-first: therapy to make cells young again trialled in a person
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Scientists are attempting to rejuvenate cells in the optic nerve (nerve fibres in red), which channels information from the retina to the brain.Credit: Thomas Deerinck, NCMIR/Science Photo Library<br>Test time has arrived: the first person has been treated in a highly anticipated gene-therapy trial that aims to coax aged cells to take on a younger identity.<br>The clinical trial is testing an innovative technique that involves turning on three genes that can ‘partially reprogram’ old cells, allowing them to behave as if they were young again. Some scientists argue that partial reprogramming could rejuvenate old organs. But this trial will test the activation of these three genes as an approach for treating disease — in this case, a form of glaucoma, a condition that can cause blindness.<br>The hope is that the proteins encoded by the genes will enable regeneration of neurons in the optic nerve, which connects the eye to the brain and is damaged in people with glaucoma. These neurons are not normally capable of regeneration. The company sponsoring the trial, Life Biosciences in Boston, Massachusetts, announced today that it had treated its first participant.<br>Is ageing a disease? The debate that could reshape medicine
The stakes are high. The trial will test the safety of the reprogramming approach, which is a lingering concern for the field. Animal studies from several labs have suggested that partial reprogramming can be done safely, but there are fears that it could tip some cells into a cancerous state.<br>“Reprogramming has a big upside if it can be used safely in people,” says Matt Kaeberlein, co-founder of Optispan, a longevity-focused preventive medicine company in Seattle, Washington. “The technology is still really early, and the potential for catastrophic side effects is high.”<br>As a result, the eye is probably a good first place to try the technique, says Kaeberlein, because the chances of life-threatening side effects are lower with changes to the eye than to some other organs.<br>Turn back the clock<br>The goal of partial reprogramming is to nudge aged adult cells back in time, restoring features of young cells without pushing the old cells so far back that they lose their specialized identity — and function — entirely. To do so, Life Biosciences harnessed three of the four genes that, in the laboratory, can be manipulated to reprogram adult cells into a stem-cell-like state.<br>In 2020, geneticist David Sinclair, who is at Harvard Medical School in Boston, Massachusetts, and his colleagues reported that activating these three genes in mice with damaged optic nerves promoted neuron regeneration and reversed vision loss in elderly mice and mice with glaucoma1. Since then, Life Biosciences has studied the approach in rodents and monkeys and has not seen serious adverse effects of the treatment, says Sharon Rosenzweig-Lipson, chief scientific officer at the company.<br>This method to reverse cellular ageing is about to be tested in humans
In the clinical trial, Life Biosciences aims to treat as many as 12 people with glaucoma and to eventually include some participants with a severe, acute condition called non-arteritic anterior ischaemic optic neuropathy (NAION), which also causes nerve damage in the eye.<br>The company relies on a virus commonly used in gene therapy to shuttle the three reprogramming genes into retinal ganglion cells, whose long arms make up the optic nerve. As an added safety feature, the system is designed so that the genes are switched on when the participant takes an antibiotic called doxycycline. If the antibiotic is stopped, the genes switch off. This strategy “gives us a lot of control”, says Rosenzweig-Lipson, providing the ability to turn the genes on and off “and not leave on expression longer than is necessary to rejuvenate the cells”.<br>True youth<br>Success in the trial would be a boon to people with glaucoma and NAION, but whether that means that modified cells are truly ‘younger’ and can be reprogrammed to enhance longevity is a bigger question, says Pete Williams, a translational neurobiologist at the Centre for Eye Research Australia in Melbourne.<br>The company is proceeding “one age-related disease at a time”, according to Rosenzweig-Lipson. “We’re not looking at whole-body rejuvenation at this point in time,” she says. “We hope to get there some day,...