Research led by Chinese scientists may lead to a potential new therapy for the currently untreatable delayed neuropathy caused by acute exposure to insecticides or chemical weapons that attack the nervous system, a study published Tuesday in the journal Cell Discovery revealed.
A research team identified a new biological mechanism responsible for the neuropathy, as well as the drugs to treat it.
Organophosphates (OP), the chemical compound found in insecticides, herbicides, and nerve agents such as sarin, were found to damage sensory neurons by activating a channel, called TRPA1, in the neuron cell membrane.
Activation of TRPA1 caused hyper-activation of the neuron, which is known to cause neuronal damage and symptoms including burning pains on the skin, loss of muscle control and paralysis.
Mice that were genetically engineered not to express TRPA1 in neuronal cells did not suffer the effects of OP poisoning that were seen in normal mice and their nerves showed no signs of damage, according to the study.
This study provides compelling evidence that TRPA1 mediates OP-induced neuropathy and that TRPA1 can be targeted effectively with existing drugs that are approved by the Federal Drugs Administration, said the study's lead author
Dr. Gao Zhaobing, from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
"Using our expertise in drug discovery we were also able to screen a Federal Drugs Administration-approved drug library of around 2,000 drugs and identify two potent drugs, duloxetine and ketotifen, which alleviated the signs of neuropathy in an animal model," said Gao.
Further research is needed to assess whether the findings are applicable to humans, according to the authors.
A research team identified a new biological mechanism responsible for the neuropathy, as well as the drugs to treat it.
Organophosphates (OP), the chemical compound found in insecticides, herbicides, and nerve agents such as sarin, were found to damage sensory neurons by activating a channel, called TRPA1, in the neuron cell membrane.
Activation of TRPA1 caused hyper-activation of the neuron, which is known to cause neuronal damage and symptoms including burning pains on the skin, loss of muscle control and paralysis.
Mice that were genetically engineered not to express TRPA1 in neuronal cells did not suffer the effects of OP poisoning that were seen in normal mice and their nerves showed no signs of damage, according to the study.
This study provides compelling evidence that TRPA1 mediates OP-induced neuropathy and that TRPA1 can be targeted effectively with existing drugs that are approved by the Federal Drugs Administration, said the study's lead author
Dr. Gao Zhaobing, from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
"Using our expertise in drug discovery we were also able to screen a Federal Drugs Administration-approved drug library of around 2,000 drugs and identify two potent drugs, duloxetine and ketotifen, which alleviated the signs of neuropathy in an animal model," said Gao.
Further research is needed to assess whether the findings are applicable to humans, according to the authors.
