One of the worlds slowly progressing terminal diseases is ALS. The treatment options for this condition are limited and there is no known cure. One of the major symptoms is the loss of motor control and this comes from the death of motor neurons that are located in the spine. Ninety percent of the diagnoses are sporadic while ten percent are linked to the following genes:
- Superoxide dismutase 1 – SOD1
In the early stages the disease presents as muscular weakness and then progresses to poor respiratory control because the diaphragm with stop functioning.
Genetically Caused ALS
Finding the various genetic causes of Amyotrophic Lateral Sclerosis (ALS) is something that is just beginning. GWAS (genome wide association studies) have identified some new genes each with different functions. Because there isn’t a unifying theory, treatment development has been confounded. Free radicals complexed with zinc or copper tend to accumulate but SOD1 prevents this. When this protein is not associated with the aforementioned metals, it become unstable and clumps up inside the neuron. These clumps of protein are called aggregations and they have become the hallmark of ALS. They have been found to remain consistent regardless of the different mutations in the genes.
Protein that is aggregated, non-functional or misfolded the cell usually removes it through degradative pathways. If these types of proteins accumulate within the cell, it can die. C9orf72, FUS, SOD1 and TDP-43 also aggregate. Remarkably, both TDP-43 and FUS, which are called TARDBP, are known as nucleic acid binding proteins and their work is to regulate the transcription of protein.
In March 19, 2016 there was research newly published in Science 1 that untangled and presented another protein associated with nucleic acids, C9orf72. The finding was of antisense increase. This means that normal transcripts are reversed in a mouse model when the protein C9orf74 has gene segments that are repeated. The result is that the RNA pieces combine and then imitate human ALS.
It has been found that discovering a system that prevents or clears protein combinations and saves neurons cannot be belittled. The treatment methods used on the various people have been successful in delaying the progression of symptoms only in some patients but not in all of them. Today, Rilutek also known as Riluzole is the only medication approved for ALS. This medication dampens the excitation of neurons and prevents some cell death. There is a great need for new treatments and this is a great avenue for active research.
Treatment for ALS Cure
There are several stem cell therapy trials planned. The brain and the spine have a variety of different cell types in them apart from neurons. It is not well understood how these supporting cells and the neurons relate. However, there are therapies in different stages of clinical development that are using Induced Pluripotent Stem Cells (iPSC), human embryonic stem cells (heSC), glial-restricted progenitor cells (GRP) and human mesenchymal stem cells (MSC). Before any human trials can begin, each one of these cell types will need to be carefully validated, manufactured, banked and characterized. The analysis will include differentiation potentials, genetic sequencing, flow cytometry and freeze/thaw survivability. All this must be up to the set FDA GMP standards.