Amyotrophic Lateral Sclerosis (ALS) is a progressive neurological disease that destroys nerve cells in the brain and the spinal cord and causes disability. Upper motor neurons send messages from the brain to the spinal cord and lower motor neurons from the spinal cord to the muscles throughout the body. ALS affects these upper and lower motor neurons located in the brain, spinal cord and brainstem. Degeneration of upper motor neurons causes tightness resulting in spasticity, whereas degeneration of the lower motor neurons causes weakness, muscle atrophy (shrinkage of the muscles) and twitching.Over time, the progressive degeneration of the motor neurons in the brain and spinal cord causes the neurons to shrink and eventually results in their demise. When the motor neurons are lost, the brain is no longer able to initiate, move and control certain muscle movements. Consequently, within a few years of diagnosis, Individuals with Amyotrophic Lateral Sclerosis experience muscles becoming smaller and weaker, affecting the ability to speak, eat, walk and perform several other daily routine tasks.
The cause behind Amyotrophic Lateral Sclerosis is still not known, however, evidence from scientific studies suggest that both genetic and environmental factors play a significant role in the development and progression of ALS. An important discovery was made in 2011 when the scientists discovered that a defect in the C9ORF72 gene is present in individuals with ALS as well as in individuals with frontotemporal dementia (FTD). This is in addition to a previously known mutation in the SOD1 gene which causes familial ALS in about 5%-10% of patients.
The most common manifestations of ALS includes familial or inherited, and sporadic ALS. Some of the other forms of ALS include Guamanian ALS and ALS-parkinsonism-dementia complex. Familial ALS is a family lineage disease which is inherited implying that it gets passed on from the parents to the children. This is a very rare type since only five to ten percent of ALS cases are inherited and generally need only one parent to carry the genetic mutation leading to disease. Familial ALS is a result of mutations existing in more than a dozen genes.
Some of the potential risk factors associated with Amyotrophic Lateral Sclerosis include:
Around twenty five to forty percent of all the familial cases are caused by a defect in a gene known as C9ORF72. Another twelve to twenty percent of familial cases result from mutation in the genes that provides instructions for the production of the SOD1 enzyme that binds to copper and zinc molecules to break down superoxide radicals. In order to avoid damage to the cells, these molecules must be broken down regularly. These molecules get accumulated in nerve cells and result in their destruction due to malfunctioning of the SOD1 enzyme. People with this type of ALS typically start showing initial symptoms at a much earlier age than individuals with sporadic ALS. Discovery of certain mutations in the genes in those with ALS suggests that changes in the processing of RNA molecules may lead to motor neuron degeneration related to ALS. Some other gene mutations reflect defects in the natural process in which malfunctioning proteins are broken down and used to build new ones through the process of protein recycling.
Sporadic Amyotrophic Lateral Sclerosis is non inherited, which means it does not run in the family and may affect anyone. It occurs in people with no history of the disorder in their families. In these cases, patients usually develop initial symptoms in their late 50s or early 60s. The cause of this type of ALS is not very well understood but may be attributed to a combination of genetic risk and environmental factors.
Genetic variations can influence one’s susceptibility to ALS even if they don’t directly cause the condition. Scientists and researchers mention chemical imbalances, disorganised immune response and protein mishandling as some of the possible causes of non-inherited forms of the disease.
Gene Mutation – Various types of genetic mutations can result in inherited ALS which causes symptoms similar to that of non-inherited ALS. Some of the scientists also believe that a person’s antibodies can at times interfere with signals from the brain to the muscles.
Chemical Imbalance (glutamate) – People with this ALS type usually have a chemical imbalance i.e. higher than normal levels of glutamate, a chemical messenger in the brain and in the spinal fluid around nerve cells. Such high levels of glutamate are known to be toxic to nerve cells and may lead to Amyotrophic Lateral Sclerosis.
Protein Mishandling – Mishandled proteins by the nerve cells can lead to a gradual accumulation of abnormal forms of these proteins in the cells, seriously affecting or killing them. According to the scientists and researchers, ALS results from the inability of protein system (ubiquilin2) to repair nerve cells that tell the muscles what to do.
Disorganised Immune Response – Disorganised immune response results in improper functioning of ubiquilin2 leading to a buildup of the damaged proteins and ubiquilin2 in critical nerve cells in the spinal cord and the brain. Sometimes the immune system of a person with ALS begins to attack the healthy cells leading to destruction and death of the nerve cells.
Environmental Toxin Exposure – Some of the possible links with environmental factors include exposure to toxins such as metals, radiation, solvents and electromagnetic fields. Exposure to lead or other substances in workplace or at home may result in ALS. Thus, there has been a two fold increase of ALS in the military as well as can be attributed to many people from the sports field that develop ALS. Studies indicate that people who have served in the military are at higher risk of ALS due to exposure to certain metals or chemicals, injuries, viral infections and intense exertion. The risk seems to be greatest for women specially after menopause.
There is no evidence that specific lifestyle related changes that could potentially decrease the risk of getting ALS. Future research might help in developing linkage between environmental factor and the risk of developing Amyotrophic Lateral Sclerosis.