Are there new treatment options for ALS? What research is being done to find a cure?
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NINDS is a component of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world.
The goals of NINDS research on ALS are to understand the cellular mechanisms involved in the development and progression of the disease, investigate the influence of genetics and other potential risk factors, identify biomarkers, and develop new and more effective treatments.
Scientists are seeking to understand the mechanisms that selectively trigger motor neurons to degenerate in ALS, and to find effective approaches to halt the processes leading to cell death. Using both animal models and cell culture systems, scientists are trying to determine how and why ALS-causing gene mutations lead to the destruction of neurons. These animal models include fruit flies, zebrafish, and rodents.
Initially, genetically modified animal models focused on mutations in the SOD1 gene but more recently, models have been developed for defects in the C9ORF72, TARDP, FUS, PFN1, TUBA4A, and UBQLN2 genes. Research in these models suggests that, depending on the gene mutation, motor neuron death is caused by a variety of cellular defects, including in the processing of RNA molecules and recycling of proteins, and structural impairments of motor neurons. Increasing evidence also suggests that various types of glial support cells and inflammation cells of the nervous system may play an important role in the disease.
In addition to animal models, scientists are also using innovative stem cells models to study ALS. Scientists have developed ways to take skin or blood cells from individuals with ALS and turn them into stem cells, which are capable of becoming any cell type in the body, including motor neurons and other cell types that may be involved in the disease. NINDS is supporting research on the development of stem cell lines for a number of neurodegenerative diseases, including ALS.
Familial versus sporadic ALS
Overall, the work in familial ALS is already leading to a greater understanding of the more common sporadic form of the disease. Because familial ALS and sporadic ALS show many of the same signs and symptoms, some researchers believe that some familial ALS genes may also be involved in sporadic ALS.
Clinical research studies supported by NINDS are looking into how ALS symptoms change over time in people with C9ORF72 mutations. Other NINDS-supported research studies are working to identify additional genes that may cause or put a person at risk for either familial or sporadic ALS.
Additionally, researchers are looking at the potential role of epigenetics in the development of ALS. Epigenetic changes can switch genes on and off, and thus can profoundly affect the human condition in both health and disease. These changes can occur in response to multiple factors, including external or environmental conditions and events. Although this research is still at a very exploratory stage, scientists hope that understanding epigenetics can offer new information about how ALS develops.
Biomarkers are biological measures that help to identify the presence or rate of progression of a disease or the effectiveness of a therapeutic intervention. Since ALS is difficult to diagnose, biomarkers could potentially help clinicians diagnose ALS earlier and faster.
Additionally, biomarkers are needed to help predict and accurately measure disease progression and enhance clinical studies aimed at developing more effective treatments. Biomarkers can be molecules derived from a bodily fluid (such as those in the blood and cerebrospinal fluid), an image of the brain or spinal cord, or a measure of the ability of a nerve or muscle to process electrical signals. The NINDS is supporting research on the development biomarkers for ALS.
New treatment options
Potential therapies for ALS are being investigated in a range of disease models. This work involves tests of drug-like compounds, gene therapy approaches, antibodies, and cell-based therapies. For example, NINDS-supported scientists are currently investigating whether lowering levels of the SOD1 enzyme in the brain and spinal cord of individuals with SOD1 gene mutations would slow the rate of disease progression.
Other NINDS scientists are studying the use of glial-restricted progenitor cells (which have the ability to develop into other support cells) to slow disease progression and improve respiratory function. Additionally, a number of exploratory treatments are being tested in people with ALS. Investigators are optimistic that these and other basic, translational, and clinical research studies will eventually lead to new and more effective treatments for ALS.
More information about ALS research supported by NINDS and other NIH Institutes and Centers can be found using NIH RePORTER (projectreporter.nih.gov), a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects.