A new study carried out by researchers at the National Institute of Neurological Disorders and Stroke (NINDS) has highlighted the potential for treating the familial form of ALS, otherwise known as Lou Gehrig’s disease. During the research, the scientists learned how a mutation in the gene which causes ALS leads to the cells accumulating damaged materials. A healthy motor neuron is able to transport any damaged components away from the cell body, but if this process is unable to happen, the defective components will collect causing the cell to become sick and die.
Over 12,000 people in the United States are affected by ALS, which is also known as Lou Gehrig’s disease, with approximately 5-10% of sufferers being affected with familial ALS, in other words, as a result of a genetic mutation from a parent. Many of these cases are caused by mutations in the gene that codes for superoxide dismutase 1 (SOD1), a very important enzyme which is found in the mitochondria of the neuron. Motor neurons in the cell that control the muscles can die when this mutation occurs, resulting in progressive paralysis.
The study’s senior author, Zu-Hang Sheng, explained that approximately 90% of the brain’s energy is generated by mitochondria, and if those mitochondria are damaged, they’re not only less efficient with their energy production, but they may also release harmful chemicals which can ultimately result in the death of cells, and neurodegeneration.
Healthy neurons have ‘storage containers’ to collect damaged mitochondria, and any associated detrimental chemicals, before they are transported via a protein called dynein to structures where they can be broken down. The team at NINDS discovered that while this process is crucial, it’s one that appears to be faulty in the nerve cells with SOD 1 mutations. This is because this particular mutant affects a critical molecule in the process, which means that the damaged mitochondria are not destroyed.
Dr. Sheng and his team used mice which had been engineered with an ALS mutation in their SOD1 genes, and by using light and electron microscopes were able to observe a build-up of damaged mitochondria in the fibres of the mice motor nerve. They also saw that this accumulation began before any overt symptoms were obvious. Using this information the team were then able to increase the amount of snapin in these neurons, which helped them to survive longer and increase the life of the mice.
It’s hoped that the model created by the team will be helpful for further research into ALS and other neurogenerative diseases.