Nav: Home

Research findings reveal potential to reverse cancer-related nerve pain

May 05, 2016

A study providing new information about neuropathic pain afflicting some 90 percent of cancer patients who have had nerve damage caused by tumors, surgery, chemotherapy or radiation indicates gene therapy as a possible treatment.

The study in rats showed transfer of a gene known as KCC2 into the spinal canal restored chloride levels gone awry after nerve injury. Results from the research at The University of Texas MD Anderson Cancer Center, were published in the May 5 online issue of Cell Reports.

The results also could have implications for treatment of chronic pain due to diabetic neuropathy and spinal cord injury since neuropathic pain caused by these conditions is associated with reduced KCC2 activity.

"We found that delivery of KCC2 produced a complete and long-lasting reversal of nerve injury-induced pain hypersensitivity by restoring chloride homeostasis," said Hui-Lin Pan, M.D., Ph.D., professor of Anesthesiology and Perioperative Medicine. "This information significantly advances our understanding of these processes and provides a promising gene therapy strategy for treating unmanageable neuropathic pain."

The proper balance of chloride, a mineral crucial for nerve cell function, is thrown off kilter by nerve damage associated with surgery or the toxic aspects of standard chemotherapies. This causes the inhibitory neurotransmitters GABA and glycine to become less effective and increases activity by excitatory nerve receptors known as NMDA receptors.

"Diminished synaptic inhibition by GABA and glycine and increased NMDA receptor activity are two key mechanisms underlying neuropathic pain," said Pan. "However the reciprocal relationship between the two is unclear. By using KCC2 gene transfer, we were able to restore chloride balance which also unexpectedly normalized NMDA receptor activity increased by nerve injury."

Chronic neuropathic pain is a major, debilitating clinical challenge that is difficult to treat. Existing analgesics including anti-depressants, opioids and gabapentinoids have limited efficacy and often produce intolerable side effects.

"The development of highly effective patient treatments with minimal effects is urgently needed," said Pan. "Our study addressed the need to change the intracellular concentration of chloride which can profoundly alter the strength and polarity of GABA and glycine."

Pan's study provided direct evidence that disrupted chloride homeostasis plays a critical role in regulation of NMDA receptors in neuropathic pain and that nerve injury increases NMDA receptor activity in the spinal cord by disrupting chloride levels.

-end-

Study team members included Linyong Li, Ph.D., Shao-Rui Chen, M.D., Lei Wen, Ph.D. and Jing-Dun Xie, M.D., all of Anesthesiology and Perioperative Medicine; and Walter Hittleman, Ph.D., Experimental Therapeutics.

The study was funded by the National Institutes of Health (RO1 NS073935 and R01 DE022015) and the N.G. and Helen T. Hawkins Distinguished Professorship for Cancer Research.

University of Texas M. D. Anderson Cancer Center
Mysterious gene transcripts after cancer therapy
Drugs that are used in cancer therapy to erase epigenetic alterations in cancer cells simultaneously promote the production of countless mysterious gene transcripts, scientists from the German Cancer Research Center now report in Nature Genetics.
Gene therapy could 'turn off' severe allergies
A single treatment giving life-long protection from severe allergies such as asthma could be made possible by immunology research at The University of Queensland.
Lipid nanoparticles for gene therapy
Twenty-five years have passed since the publication of the first work on solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) as a system for delivering drugs.
New gene therapy for pseudarthrosis trialed at Kazan University
A team headed by Professor Albert Rizvanov, director of the Gene and Cell Technologies Open Lab, created a gene therapy drug that encodes growth factors for the stimulation of blood vessel and bone formation.
WSU researcher develops safer gene therapy
A Washington State University researcher has developed a way to reduce the development of cancer cells that are an infrequent but dangerous byproduct of gene therapy.
New gene therapy prevents muscle wasting associated with cancer
A new gene therapy could be used to prevent the loss of muscle mass and physical strength associated with advanced cancer
On the path to controlled gene therapy
The ability to switch disease-causing genes on and off remains a dream for many physicians, research scientists and patients.
Gene therapy against brain cancer
A team from the International School for Advanced Studies (SISSA) in Trieste has obtained very promising results by applying gene therapy to glioblastoma.
First gene therapy successful against human aging
Elizabeth Parrish, CEO of Bioviva USA Inc. has become the first human being to be successfully rejuvenated by gene therapy, after her own company's experimental therapies reversed 20 years of normal telomere shortening.
Designing gene therapy
Scientists in the Barabas group at EMBL have increased the efficiency of a genome-engineering tool called Sleeping Beauty, which is showing promise in clinical trials for leukemia and lymphoma immunotherapies.

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.

Now Playing: Radiolab

Truth Trolls
Today, a third story of folks relentlessly searching for the truth. But this time, the truth seekers are an unlikely bunch... internet trolls.


Now Playing: TED Radio Hour

Rethinking School
For most of modern history, humans have placed smaller humans in institutions called schools. But what parts of this model still work? And what must change? This hour, TED speakers rethink education.TED speakers include teacher Tyler DeWitt, social entrepreneur Sal Khan, international education expert Andreas Schleicher, and educator Linda Cliatt-Wayman.