Amyotrophic lateral sclerosis (ALS),
or motor neuron disease, in English-speaking countries better known as Lou Gehrig’s disease, is a slowly progressing, incurable neurodegenerative disease in which both the upper cerebral cortex (motor cortex) and the lower (the anterior horn of the dorsal brain and nucleus of cranial nerves) of motor neurons, which leads to paralysis and subsequent muscle atrophy.
Clinically, this manifests itself as a gradual loss of the ability to talk, swallow and even breathe.
The existing therapeutic possibilities for influencing this disease are extremely limited and only moderately slow the process. In the focus of attention and study until now, there were questions of symptomatic treatment of patients with ALS. A lot of research is also devoted to studying the causes of the onset and progression of the disease.
Future of effective treatment regimens for patients with ALS.
The purified pool of stem cells from the bone marrow of an adult human is modified into cells that produce growth factors, which in turn have shown the ability to activate reparative processes in nerve cells. Subsequently, modified stem cells were implanted into the muscles, which, with the help of genetic engineering, induced symptoms of ALS, which is a common technique for modeling the pathophysiology of ALS in studies on the disease.
Stem cells are modified into cells that produce endothelial vascular endothelial growth factor (VEGF), a protein that activates angiogenesis. It was found that an increase in the synthesis of VEGF promoted an increase in the survival of subjects with ALS and delayed the onset of the disease. The research leader Masatoshi Suzuki in his previous work has identified the positive effect of another growth factor, the glial cell line-derived neurotropic factor (GDNF), on prolonging the viability of neurons. According to him, significant results in the study were achieved with the use of stem cells that produce both growth factors. Taking into account such parameters as the time of onset of the disease development, overall survival and preserved muscular function, the effect of two growth factors – VEGF and GDNF – was significantly more pronounced than each of them separately.
The current view on the pathophysiology of ALS is the assumption that the main process of massive neuronal damage is localized in close proximity to the spinal cord, which is the conductor of nerve impulses from the brain to other organs and systems. However, the study found that with ALS, the axonal part of the neuron, directly in contact with the muscle, is primarily damaged. Stem cells were not modified into neurons during the experiment, but were transformed into growth factor cells to activate the survival of nerve cells. Modified stem cells functioned in the subjects for approximately 9 weeks – a sufficient period for the manifestation of a positive effect on the course of the disease.
The concept of maintaining the viability of neurons in ALS promises a higher therapeutic effectiveness in comparison with other approaches aimed at the formation of stem cells from new neurons in exchange for dead nerve cells. Motor neurons (motor neurons) have very long axonal processes, due to the specificity of their function – ensuring transmission of nerve impulses to skeletal muscles through synaptic connections – and the problem of replacing such neurons is quite difficult. It is much more promising to concentrate efforts on finding ways to preserve the viability of neurons by using the same factors that participate in the structural formation of the human body, which has been successfully demonstrated in this study.
The use of adult stem cells allowed scientists to avoid the problems they had encountered in previous works.
When using stem cells, any risks were eliminated, which also affected clinical relevance, since stem cells from blood or fat can be used to treat this disease.