Summary: Transplanting GABAergic cells derived from human-induced pluripotent stem cells into mice resulted in safe, lasting, and effective relief from extreme neuropathic pain. Researchers hope to begin human testing within five years.
Source: University of Sydney
Researchers at the University of Sydney have used human stem cells to make pain-killing neurons that provide lasting relief in mice, without side effects, in a single treatment.
The next step is to perform extensive safety tests in rodents and pigs, and then move to human patients suffering chronic pain within the next five years.
If the tests are successful in humans, it could be a major breakthrough in the development of new non-opioid, non-addictive pain management strategies for patients, the researchers said.
“We are already moving towards testing in humans,” said Associate Professor Greg Neely, a leader in pain research at the Charles Perkins Centre and the School of Life and Environmental Sciences.
“Nerve injury can lead to devastating neuropathic pain and for the majority of patients there are no effective therapies. This breakthrough means for some of these patients, we could make pain-killing transplants from their own cells, and the cells can then reverse the underlying cause of pain.”
Published today in the peer-reviewed journal Pain, the team used human induced pluripotent stem cells (iPSC) derived from bone marrow to make pain-killing cells in the lab, then put them into the spinal cord of mice with serious neuropathic pain. The development of iPSC won a Nobel Prize in 2012.
“Remarkably, the stem-cell neurons promoted lasting pain relief without side effects,” co-senior author Dr Leslie Caron said. “It means transplant therapy could be an effective and long-lasting treatment for neuropathic pain. It is very exciting.”
John Manion, a PhD student and lead author of the paper said: “Because we can pick where we put our pain-killing neurons, we can target only the parts of the body that are in pain. This means our approach can have fewer side effects.”
The stem cells used were derived from adult blood samples.
The total cost of chronic pain in Australia in 2018 was estimated to be $139.3 billion.
[divider]About this neurology and genetics research article[/divider]
Source: University of Sydney Media Contacts: Elissa Blake – University of Sydney Image Source: The image is in the public domain.
Neuropathic pain causes severe suffering, and most patients are resistant to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here, we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated human induced pluripotent stem cell-derived GABAergic (iGABAergic) neurons provide significant, long-term, and safe relief from neuropathic pain induced by peripheral nerve injury in mice. Furthermore, iGABAergic neuron transplants survive long term in the injured spinal cord and show evidence of synaptic integration. Together, this provides the proof in principle for the first viable GABAergic transplants to treat human neuropathic pain patients.
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