Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects a very specific group of neurons: the neurons for voluntary motor function, also known as motor neurons. They are located in the brain and spinal cord and are responsible for controlling the muscles. These motor neurons are destroyed by the disease. This results in progressive muscle paralysis. Patients may become dependent on a wheelchair, but later in the course of the disease they also have difficulty speaking and swallowing. In the final stage, paralysis of the respiratory muscles also occurs. In other words, they do not have access to the outside world by language, writing, mimics, gesture and posture.
The disease is rare: Every year, about three out of 100,000 people in Europe develop amyotrophic lateral sclerosis. There are currently about 8,000 to 9,000 patients in Germany, and about 2,500 people in this country are newly diagnosed with ALS each year. The individual risk for dying of ALS is estimated with 1:400. In most cases, people develop this disease between the ages of 60 and 80. But younger people can also be affected: Probably the most famous ALS patient, Stephen Hawking, was just 21 years old when he was diagnosed with the disease, which – like many juvenile cases - was slowly progressive. Hawking, a physicist, lived with the disease for many decades. However, in most affected individuals, ALS leads to death within a few years. Men are affected by the disease slightly more often than women.
The characteristic phenotype of ALS is characterized by progressive muscle paralysis, which starts focally and then propagates continuously over the entire body. It often begins in the hands, usually only on one side, where it is often noticed due to difficulty gripping or writing. Just as often, the legs can be affected first. About a quarter of patients first experience problems swallowing or speaking (so-called bulbar symptoms).
How ALS manifests itself depends on which type of motor neuron is damaged first. Disorders of the eye muscles or the compressing muscles of the bladder and intestines are not among the early symptoms.
Sensory perception, that is, the sense of touch and temperature, tasting, smelling, hearing and seeing, is still intact. Consciousness and the ability to think are usually not affected either: as the disease progresses, patients can no longer communicate with those around them, although their mind is still lucid. However, cognitive changes and what is called frontotemporal dementia occur in around five percent of all those affected. How aggressively and how quickly ALS progresses in each individual case and when it will lead to death cannot be predicted individually as of yet, as the courses of progression can be very different.
In about five percent of ALS patients, the disease is inherited and runs in families. Due to a gene mutation, the cell metabolism of the affected person is disturbed, which ultimately leads to damage of the nerve cells. In the other 95 percent, which is the vast majority of the condition, the causes of motor neuron degeneration are still not understood well enough.
A treatment that could stop the progression of ALS or cure the disease does not exist yet. The disease is always fatal. Therapy is therefore primarily aimed at alleviating discomfort and making everyday life easier with suitable aids. The focus is on maintaining the quality of life and self-determination of those affected as far as possible. This includes respiratory support and treating the worst prognostic factor, katabolism.
The only approved drug therapy currently available is Riluzole, which can delay the course of the disease and thereby prolong survival. Important additional measures include ergotherapy, speech therapy, ventilatory and nutritional support.
As far as the hereditary form of ALS is concerned, research is currently being conducted at the DZNE to reduce the effect of the disease-causing genes with drugs that influence gene regulation. Researchers at the DZNE are also committed to better understanding the mechanisms of the disease behind ALS. They are also targeting inflammatory processes that may play a role in neuron death. In addition, DZNE scientists are focusing on the relationship between ALS and frontotemporal dementia. With their fundamental insights about the disease, they are paving the way to find starting points for new therapies. Currently, more than five therapeutic studies with unique new methods of action and medications are being conducted at the DZNE.
Other DZNE scientists are looking for suitable biomarkers, meaning typical measurable changes in the blood or cerebrospinal fluid, for example, to better predict the progression of the disease and which can support to measure the effects of interventional drugs.
It was the French physician Jean-Martin Charcot who first described amyotrophic lateral sclerosis about 150 years ago. Charcot was born in Paris in 1825. Since he stood out as the best student among his four brothers, his father chose him for higher education. Charcot studied medicine, later became chief physician at the Hôpital de la Salpêtrière in Paris, and is considered the founder of modern neurology. He also made his mark in science by successfully matching clinical symptoms with anatomical findings, for example in the case of multiple sclerosis, from which he distinguished ALS as an independent disease. It was initially called Maladie Charcot, meaning Charcot's disease, after the first person who described it. Charcot described the changes in nerve tissue affected by ALS in great detail. Moreover, he predicted at that time that it would take a long time before it would be possible to treat this disease.