Stem selection
Expectations were met: from the skin of a baby suffering from a rare fatal disease, it was possible to create a cell line that allowed us to find the right drugs. However, the doctors did not have time to help the child.
Modern pharmaceutical giants can only envy scientists of the XVIII–XIX centuries. Then there were no ethical committees, rules and regulations governing clinical trials of new drugs and treatment methods. It helped the patient – well, it didn't help – he would have died anyway. Now drug developers have to go all the way under strict control from the very beginning. And it all starts with a model, a "guinea pig", on which you can study the mechanisms of development and test test substances.
But it is also a sin for modern specialists to complain, because the palette of methods by which one can recreate a particular human disease on animals is huge. You can turn off the gene at the zygote stage, or you can temporarily block its work in individual cells. You can do such manipulations repeatedly with all suspicious genes, and then try to understand how the absence of a particular protein affects the treatment of a disease or the reaction of cells to a new drug.
Allison Ebert and her colleagues at the University of Wisconsin–Madison have developed a new way of "guessing" - this time on stem cells.
The object of study was spinal amyotrophy – hereditary muscular dystrophy, in which, for reasons not fully known, motor neurons of the spinal cord die massively. Since these nerve cells are responsible for controlling skeletal muscles, after a while the child can not move, not even breathe.
The search for ways to treat this disease is complicated by the lack of a suitable biological model. Animals do not suffer from spinal amyotrophy, and it is not such a simple procedure to isolate individual neurons from the children's spinal cord. In addition, then we would have to look for ways to multiply nerve cells in vitro.
Ebert and co-authors of the publication in Nature decided: if neurons cannot be isolated, let's grow them from the child's own cells. Moreover, for a year now there has been no need to go for stem cells in the central nervous system or in the bone marrow. A small incision on the skin is enough, and specialists have an almost unlimited number of ordinary fibroblasts in their hands, which make up the connective tissue. Small manipulations with the genome – and this is no longer a fibroblast, but an "induced" embryonic stem cell, from which, with the help of growth factors, you can get both neurons and cells of bone or cartilage tissue, or the same fibroblasts.
Only Ebert did not limit herself to one culture, but made two at once – both from the skin of a sick child and from the skin of his healthy mother. Within a month, the cells behaved approximately the same, but after reaching this period, the "children's" neurons began to die massively due to a lack of SMN protein, which supports the viability of nerve cells.
This is where the model showed itself in all its glory: it was worth adding valproic acid or tobramycin, as the SMN level increased, although it did not reach the norm. Maternal "healthy" neurons did not respond to these drugs in any way. However, by that time there was no help for the child.
Ebert has no doubt that thanks to their discovery, the list of drugs for the treatment of spinal amyotrophy will significantly expand in the near future.
Maybe it will even be possible to choose the appropriate method of gene therapy, because replacing a "defective" section of DNA is the only way to completely cure a congenital, that is, genetically determined, disease.
But it's also not worth waiting for this to happen tomorrow. An example of this is Duchenne myodystrophy, the mechanisms of development of which have been studied for a long time, and there is even a line of mdx mice in which the disease develops according to the same scenario as in humans. Clinical trials of gene therapy have begun.