Key Takeaways
- Cambridge scientists have developed miniature human brain and spinal cord circuits, revealing that previously irreversible damage may be reversible.
- Research indicates that axon regrowth is possible in younger neural tissue but limited as the neurons mature.
- A hormone drug, lynestrenol, has been identified as a potential candidate for enhancing axon regeneration after damage.
Research Breakthrough in Neural Regeneration
Scientists at the University of Cambridge have achieved a breakthrough by growing miniature circuits in the lab that emulate the connections between the brain and spinal cord. This innovative model has shown that what was once thought to be irreversible damage in these connections may actually be reversible.
Neurons, or nerve cells, transmit information throughout the body, playing a critical role in movement. Each neuron contains axons, which act as cables to relay signals to other neurons and activate muscle contractions. Regrettably, once damage occurs in the central nervous system—due to trauma or diseases like motor neurone disease or multiple sclerosis—the ability to regrow axons diminishes, leading to permanent disabilities, including paralysis.
In 2021, Dr. András Lakatos and his research team created ‘mini brains’ using human stem cells. These pea-sized organoids were designed to mimic parts of the human cerebral cortex and were essential for studying molecular issues in motor neurone disease. Their latest research, published in Cell Reports, takes this effort further by constructing a precise model of interconnected brain and spinal cord tissues.
The research’s structure maintains a separation between brain and spinal cord organoids. This configuration allowed the scientists to witness the growth of nerve fibers from brain organoids toward spinal cord organoids, effectively creating a working circuit. Remarkably, this circuit could induce muscle contractions, demonstrating functionality.
The study tracked these organoids for over a year and noted that axon regeneration remained possible until around day 150, which corresponds with mid-pregnancy development. After this point, regrowth drastically decreased. George Gibbons, the study’s first author, remarked that neurons from younger organoids were more capable of regrowing their fibers post-injury, revealing an inherent limitation in growth as neurons mature in the central nervous system.
The researchers further analyzed gene expression in the neurons bridging the brain and spinal cord, identifying a network of genes that restricts axon growth during neuronal maturation. Promisingly, inhibiting certain genes in this network restored the ability of axons to grow.
As part of this exploration, the team reviewed drug compounds targeting the identified gene network and discovered lynestrenol, a hormone drug used for treating menstrual disorders. Testing this drug on damaged neurons resulted in a significant improvement in axon growth.
While challenges such as scar tissue and inflammation complicate regeneration, focusing on neuron-specific issues is vital. Evidence suggests that less mature neurons can often grow despite adverse injury conditions.
Dr. Lakatos, who leads the research, emphasized that neurotransmission signals from the brain rarely recover following damage, leading to permanent paralysis. Importantly, their model highlights that limited regeneration occurs during development, yet this limitation can be reversed, offering hope for potential treatments for previously untreatable conditions.
The implications of this research extend beyond axon regeneration; organoid models, often referred to as ‘mini organs’, contribute significantly to understanding human biology and disease. At Cambridge, researchers employ organoids in various other fields, such as liver repair and developmental studies.
This research received funding from the UK Research and Innovation Medical Research Council and Spinal Research. Spinal Research’s Chief Executive, Louisa McGinn, expressed optimism for the millions living with spinal cord injuries, indicating that the next few years could provide groundbreaking therapeutic options that were previously unimaginable.
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