In 1999, the Miami Spine Project reported the first experience with producing GABA with cell lines injected into the spinal fluid. Now, there is more good news. We have been waiting for the first big break. Ziconotide seemed to be it, but has side effects in many at effective doses. Now comes hope from another direction. Thank heaven for the cellular biologists.
The Miami Spine Project first teased us a little with the report in 1999 of GABA producing cells injected into spinal fluid. See Eaton MJ et al Cell Transplant. 1999 Jan-Feb;8(1):87-101. “Transplants of neuronal cells bioengineered to synthesize GABA alleviate chronic neuropathic pain”. In that article the authors used rat derived material.
The rat cell line was “RN33B, derived from E13 brain stem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat GAD67 cDNA (glutamate decarboxylase, the synthetic enzyme for GABA)” Transfection is usually done by taking a cell culture, grafting superamounts of genetic material (DNA) for some desired substance (eg. glutamate decarboxylase) into a benign virus, and then transferring the genetic code into the cells in culture by infecting them with the virus. This “transfects” or transfers by infection, the desired genetic traits.
Next, Eaton et al really piqued our curiosity by showing that chromaffin cells, which come from the adrenal medulla, could be used in more or less the same way. Chromaffin cells, named for their affinity for chromium stain, produce adrenaline, but here is where it gets interesting, they also produce enkephalins, the small opiate peptides which give a “high”.
Eaton has been knocking on this door for some time. See the chromaffin cell study using rat and bovine cells in ” Initial characterization of the transplant of immortalized chromaffin cells for the attenuation of chronic neuropathic pain”.Cell Transplant. 2000 Sep-Oct;9(5):637-56. That adrenal cells could help pain is not quite as stunning as it appears. Adrenal cells bear some strange affinity with brain cells. Long ago, the Japanese tried to create a biological computer using adrenal cells cultured in grooves cut in glass. They could not get neurons to grow, so they grew adrenal cells and then converted them to neurons, by the application of a little acid. Amazing, isn’t it.
Now, these studies are coming to maturity with the use of human cell lines and the news appears to be all good.
The Miami group’s newest article is clever at several levels in study design. The study cites the “daunting” difficulty in treating pain after spinal cord injury. Then, the details are revealed.
First, Using human NT2 cells a new cell line of neurons was developed, known as hN2.17, which express GABA,a pain inhibitor but do not evoke release of growth factors nor any tumorogenic growth factors.
Second, Injury to rat spinal cord was induced with a mixture of AMPA (see AMPA using SEARCH at this site) and Quisqualic acid, which is an agonist of metabotropic exciter receptors. This caused thermal and mechanical hyperalgesia (experimental central pain).
Third, the hN2.17 cells were injected into the subarachnoid space
Fourth, a very marked improvement in pain behavior was observed and a certain number of the injected cells remained viable.
The information was authored by Eaton MJ, Wolfe SQ, Martinez M, Hernandez M, Furst C, Huang J, Frydel BR, Gomez-Marin O. J Pain. 2007 Jan;8(1):33-50. We note in passing the new model for creation of central pain; namely, that central pain could be induced using AMPA and upregulating metabotropic receptors (usually involves receptors which respond to glutamate, the primary pain exciter). This has to have some implications how central pain develops in the ordinary course of things.
The research was done at the VA Hospital and at the University of Miami, the Miami Project to Cure Paralysis.
Now, if all of these reported results can be duplicated, this is a VERY significant advance. It is the sort of finding which is almost too good to be true. Human studies are sure to follow.
We congratulate these researchers and the Miami Spine Project for such brilliant work.
