NIH High-Risk, High Reward Research Program on ALS
The National Institutes of Health is investing $25 million over 5 years in a program to spur innovative research on ALS. The Accelerating Leading-edge Science in ALS (ALS2) aims to answer critical questions about this disease. ALS2 will be part of the NIH Common Fund’s High-Risk, High-Reward (HRHR) research program, through its Transformative Research Award initiative. ALS2 will take a three-pronged approach to improve understanding of ALS:
- Adapt emerging tools and technologies from neuroscience and cell biology to identify what causes ALS at the molecular level, and how the disease progresses, leading to new therapeutic strategies.
- Attract new talent from a range of scientific disciplines, including neuroscience, cell biology, bioengineering, genomics, chemistry, biophysics, environmental health sciences, and computational science.
- Examine biological similarities between ALS and motor neuron disease in other neurodegenerative disorders, including frontotemporal dementia, chronic traumatic encephalopathy, Kennedy’s disease, spinal muscular atrophy, and primary lateral sclerosis.
For more information, please visit: NIH Common Fund High-Risk, High-Reward Research Program
The goals of NINDS’s ALS research 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 treatments.
Cellular defects. Ongoing studies seek to understand the mechanisms that selectively trigger motor neurons to degenerate in ALS, which may lead to effective approaches to halt this process. Research using cellular culture systems and animal models suggests that motor neuron death is caused by a variety of cellular defects, including those involved in protein recycling and gene regulation, as well as structural impairments of motor neurons. Increasing evidence also suggests that glial support cells and inflammation cells of the nervous system may play an important role in ALS.
Stem cells. Scientists are turning skin cells of people with ALS into stem cells that are capable of becoming any cell type, including motor neurons and other cells which may be involved in the disease. NINDS-funded scientists are using stem cells to grow human spinal cord sections on tissue chips to help better understand the function of neurons involved in ALS.
Genetics and epigenetics. A large-scale collaborative research effort supported by NINDS, other NIH institutes, and several public and private organizations is analyzing genetic data from thousands of individuals with ALS to discover new genes involved in the disease. By using novel gene editing tools, researchers are now able to rapidly identify new genes in the human genome involved in ALS and other neurodegenerative diseases.
Additionally, researchers are looking at the potential role of epigenetics in ALS development. Epigenetic changes can switch genes on and off, which can greatly impact both health and disease. Although this research is exploratory, scientists hope that understanding epigenetics can offer new information about how ALS develops.
Biomarkers. NINDS supports research on the development of biomarkers—biological measures that help identify the presence or rate of progression of a disease or the effectiveness of a therapeutic intervention--for ALS..
New treatment options. This work involves tests of drug-like compounds, gene therapy approaches, antibodies, and cell-based therapies in a range of disease models. Additionally, a number of exploratory treatments are being tested in people with ALS.
Information from the National Library of Medicine’s MedlinePlus
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal disease that affects the nerve cells (neurons) in that brain and spinal cord that control voluntary muscle movement. Our voluntary muscles produce movements like walking, breathing, chewing, and talking. Nerve cells called motor neurons--that connect from the brain and spinal cord to the rest of the body--begin to degenerate and die, and stop sending messages to muscles. The muscles gradually weaken, waste away, and twitch, and the brain can't start and control voluntary movement. Symptoms are usually first noticed in the arms and hands, legs, or swallowing muscles. People with ALS lose their strength and become unable to move their arms and legs, and to hold the body upright. Some individuals eventually can't breathe on their own. Although ALS doesn't usually impair a person's mind or personality, several recent studies suggest that some people with ALS may develop cognitive problems involving word fluency, decision-making, and memory. Most cases of ALS happen with no known cause, while a small percentage of cases are inherited.
No cure has yet been found for ALS. However, the drugs riluzole and edaravone have approved by the Food and Drug Administration (FDA) to treat ALS. Riluzole prolongs life by 2-3 months but does not relieve symptoms. Edaravone can slow the clinical decline in daily functioning of people with ALS. The FDA has also approved the NeuRx Diaphragm Pacing System, which uses implanted electrodes and a battery pack to cause the diaphragm (breathing muscle) to contract, to help certain individuals who have ALS before the onset of severe respiratory failure. Other treatments are desig ned to relieve symptoms and improve the quality of life for people with ALS. Drugs are available to help individuals with spasticity, pain, panic attacks, and depression. Physical therapy, occupational therapy, and rehabilitation may help to prevent joint immobility and slow muscle weakness and atrophy. Individuals with ALS may eventually consider forms of mechanical ventilation (respirators).
Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Individuals have increasing problems with moving, swallowing, and speaking or forming words. Eventually people with ALS will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. In later stages of the disease, individuals have difficulty breathing as the muscles of the respiratory system weaken. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms. However, about 10 percent of those individuals with ALS survive for 10 or more years.