University of Cambridge breakthrough could help the brain and spinal cord repair themselves

A breakthrough from the University of Cambridge is offering new hope for one of medicine’s most stubborn challenges: repairing damage to the brain and spinal cord. By growing miniature connected brain and spinal cord circuits in the laboratory, scientists have uncovered evidence that the loss of the human nervous system’s ability to repair itself may not be permanent after all.

The study reveals that a built-in genetic program gradually shuts down the ability of nerve fibers to regrow during human development. Even more remarkably, researchers found ways to reverse that shutdown in lab-grown human neurons, restoring their capacity for repair. The findings could eventually help scientists develop treatments for spinal cord injuries and neurological diseases that currently leave patients with lifelong disabilities.

Every movement, from taking a step to picking up a cup, depends on communication between the brain and spinal cord. These messages travel through long nerve fibers called axons, which act like biological cables connecting different parts of the nervous system.

During early development, axons grow rapidly and form complex networks throughout the body. This remarkable growth allows the brain and spinal cord to establish the connections needed for movement, sensation, and thought.

But something changes as humans mature.

At some point during development, neurons in the central nervous system largely lose their ability to regenerate damaged axons. As a result, injuries to the brain or spinal cord often become permanent. This loss of repair capacity contributes to paralysis after spinal cord trauma and plays a role in diseases such as motor neurone disease and multiple sclerosis.

Scientists have long known that adult human neurons struggle to regrow after injury. What remained unclear was exactly when this ability disappears and whether it could be restored.

To answer these questions, researchers led by Dr András Lakatos at the University of Cambridge created an advanced laboratory model that recreates the connection between the human brain and spinal cord.

The work builds on earlier research from the group, which developed brain organoids, often called “mini brains,” using human stem cells. These three-dimensional structures mimic important features of the developing cerebral cortex.

For the new study, the team went further. They created separate brain and spinal cord organoids and positioned them apart from one another, mimicking the way these tissues exist in the human body.

The researchers then watched as axons from the brain organoids extended across a gap and connected with spinal cord tissue. The resulting system formed functioning neural circuits capable of transmitting signals.

To demonstrate that these connections worked, the team added tiny clusters of human muscle cells. When the brain side of the circuit was stimulated, signals traveled through the spinal cord organoid and triggered muscle contractions.

The result was a functioning laboratory-grown model of the pathway that allows the brain to control movement.

The scientists maintained these connected systems for more than a year, allowing them to observe how neurons changed as they matured.

They examined brain organoids at different developmental stages, including tissues aged 75, 100, 150, and 290 days.

The findings revealed a dramatic shift.

Up to roughly 150 days of development, corresponding to the middle stages of pregnancy, neurons retained a strong ability to regrow damaged axons. After that point, regenerative capacity declined sharply.

When researchers injured neurons from younger organoids, the cells readily produced new nerve fibers. In contrast, neurons from older organoids showed much poorer recovery.

“Neurons taken from less mature organoids regrew long fibres 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 from the Department of Clinical Neurosciences at the University of Cambridge and the study’s first author.

The results suggest that the inability of adult neurons to repair themselves is not simply a consequence of injury. Instead, it appears to be programmed into the cells during development.

To understand what drives this transition, the team analyzed gene activity in neurons that connect the brain and spinal cord.

Using advanced computational methods, they identified networks of genes that became increasingly active as neurons matured and formed synaptic connections.

Several of these genes regulate important cellular functions, including cytoskeleton organization, synapse formation, metabolism, protein production, and DNA repair.

Together, they appear to act as a molecular switch that limits axon growth once developmental wiring is complete.

The researchers also found links to PTEN, a gene already known to suppress nerve regeneration.

When they blocked PTEN using a laboratory compound called VO-OHpic, the results were dramatic. Damaged neurons began regrowing more rapidly, and growth cone movement increased nearly threefold shortly after injury.

These findings confirmed that intrinsic genetic programs, rather than external barriers alone, play a major role in restricting regeneration.

Instead of focusing on a single gene, the team searched for medicines that could broadly reverse the mature genetic state of neurons.

Using computational screening methods, they analyzed hundreds of approved and experimental compounds that might influence the identified gene networks.

The search produced 323 potential candidates.

Researchers selected six licensed drugs for testing based on safety data and predicted effectiveness.

One compound emerged as the clear frontrunner: lynestrenol.

Lynestrenol is a hormone-based medication that has been used for decades as a contraceptive and for treating certain menstrual disorders.

When applied to injured mature neurons, lynestrenol significantly increased axon regrowth. In one experiment, treated neurons produced axons more than twice as long as those in untreated cells.

The findings suggest that mature human neurons can regain some of their lost regenerative capacity when key developmental pathways are altered.

Scientists caution that the research remains at an early stage. The experiments were conducted in laboratory-grown tissues rather than patients. The model also lacks immune cells, blood vessels, and other components found in living nervous systems.

Even so, the study challenges a long-held assumption that regeneration failure in the human central nervous system is irreversible.

“When the brain and spinal cord are damaged, the nerve fibres 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 Dr András Lakatos.

He added: “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.”

The study also highlights the increasing importance of organoids in medical research.

Animal models have helped scientists understand nerve regeneration for decades. However, human neurons often behave differently than those of rodents, creating challenges when translating discoveries into treatments.

Human organoids help bridge that gap. They allow researchers to study human biology directly while reducing reliance on animal experiments.

“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,” Lakatos said.

This research provides a powerful new platform for studying how human neurons develop, connect, and respond to injury. By identifying the genetic programs that limit regeneration, scientists now have specific targets for future therapies aimed at restoring movement after spinal cord injury or neurological disease.

The findings may also accelerate drug discovery. Because researchers successfully identified an existing licensed medication that boosts axon regrowth, future studies may uncover additional approved drugs that can be repurposed more quickly than entirely new treatments.

Beyond spinal cord injuries, the organoid system could help researchers investigate diseases such as motor neurone disease, multiple sclerosis, and other conditions involving damaged neural connections. While clinical applications remain years away, the work demonstrates that the human nervous system’s capacity for repair may be more flexible than previously believed, offering renewed hope for patients facing conditions once considered permanently disabling.

Research findings are available online in the journal Cell Reports.

The original story "University of Cambridge breakthrough could help the brain and spinal cord repair themselves" is published in The Brighter Side of News.

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