CAMBRIDGE — Researchers at the University of Cambridge discovered that human neurons lose their ability to regrow damaged axons around day 150 of development—a stage roughly corresponding to mid-pregnancy—and identified both a gene network and a drug that can restore this regrowth capacity in lab-grown models of the human brain and spinal cord. The findings were published in a 2026 study in Cell Reports.

The team created miniature, lab-grown brain and spinal cord systems that mimic how movement signals travel through the nervous system. These organoid models were functional enough to trigger contractions in tiny clusters of muscle cells, demonstrating their physiological relevance.

Using these models, the researchers observed that neurons taken from less mature organoids regrew long fibers after injury, but those from more mature organoids showed a sharp drop in regrowth capacity. "Neurons taken from less mature organoids regrew long fibers after injury, but those from more mature organoids showed a sharp drop in their ability to regrow. In other words, poor regeneration is built into human neurons as they mature in the central nervous system," said George Gibbons, a researcher in the Department of Clinical Neurosciences at the University of Cambridge.

The team identified a network of genes that acts as a biological switch limiting axon growth as neurons mature and form synapses. When key regulators within this gene network were blocked, the neurons regained their ability to grow axons.

Researchers also tested lynestrenol, a hormone drug approved for certain menstrual disorders and contraceptive use, and found it improved axon regrowth in damaged neurons. "When the brain and spinal cord are damaged, the nerve fibers that carry movement signals from the brain to the spinal cord rarely grow back. That's why paralysis is usually permanent. But we didn't know exactly when the ability of axons to regenerate becomes limited. Our model provides a good indication that this block happens during development, and it can still be reversed after this point," said András Lakatos, senior author and researcher at the Department of Clinical Neurosciences, University of Cambridge.

"Lynestrenol itself may not be the answer to spinal cord repair, but it shows us that, in principle, it should be possible to directly target human neurons and regenerate their axons. Although we still need to show that this strategy will also help to re-establish appropriate connections between the brain and spinal cord cells, this gives us hope that one day we may be able to treat conditions previously thought untreatable," Lakatos said.

"Much of what we know about nerve regeneration comes from rodents, whose neurons behave differently from human neurons. Our sophisticated organoid models help bridge the knowledge gap from animal models to what we see in patients. They are also an important contribution to efforts to reduce the use of animals in research," he added.