Amyotrophic Laternal Sclerosis (ALS) - A Rare Disease More Common in EU&US

Epidemiological studies have found that the incidence of ALS is 1.9/105, the prevalence is 4.5/105, and the average age of onset is 55 years (Incidence: proportion of new patients per year; Prevalence: ratio of existing patients to total population).

In addition, the data shows that the incidence rate in Europe and the United States is higher, at 2.6/105, and the prevalence rate is almost double, at 7-9/105. ALS is more common in men than women, and more common in whites, among whom Anglo-Saxons and Germanics have significantly higher rates than Latinos.

In contrast, the incidence is lower among asians, being as low as 0.8/105 in East Asia and 0.7/105 in South Asia. Because of this, Europe and the United States have invested heavily in the research of this disease, accounting for more than 80% of the world's research projects on ALS.

ALS is a motor neuron disease (MND), which is a group of neurological disorders that selectively affect motor neurons with secondary damage to muscles. In a normal body, there is a motor nervous system that works in an orderly manner, as shown below:

First, the motor cortex and brainstem in the brain transmit signals for active movement. The motor cortex is responsible for planning, initiating, and directing voluntary movements; the brainstem is responsible for rhythmic, stereotyped movements, such as breathing and postural control, which basically does not require the participation of active consciousness.

As supplementary areas of the brain, the basal ganglia is responsible for the initiation of intended movement and suppression of unwanted movement; the cerebellum is responsible for coordinating the functions of various departments during the whole process of movement and is in charge of coordinating ongoing movement.

Signals from the motor cortex and brainstem are transmitted to the spinal cord or motor neuron pools. Some information goes directly to the motor ganglia, and some is transmitted to the motor neuron pools through the spinal cord.

Then, the motor neurons in the motor neuron pools begin to order the muscles to work. At the same time, the spinal cord is responsible for sensorimotor integration and central pattern generation through local circuit neurons, handling simple problems and reporting complex problems to the motor cortex or brain stem for instructions.

According to the classification of the motor nervous system, ALS can be divided into two types: LMN-impaired and UMN-impaired.

The key to distinguishing the two is that the LMN-impaired type occurs directly in the neurons that communicate with the muscle from the beginning, so the symptoms are flaccid paralysis, hypomyotonia and hyporeflexia, convulsions and spasms, and a negative Babinski sign. The UMN-impaired type results in spastic paralysis, hypermyotonia and hyperreflexia, disuse-atrophy, and a positive Babinski sign.

In addition, muscle atrophy of the LMN-impaired type occurs earlier and more rapidly than that of the UMN-impaired type, and the latter has a certain degree of muscle hyperfunction in the early stage.

The lesions of ALS are mainly located in motor neurons, but diagnosis is not easy because its symptoms are similar to those of many cerebellar and muscle atrophy-related diseases. In particular, UMN-impaired ALS is often confused with primary lateral sclerosis (PLS), which is also a UMN-impaired disease. LMN-impaired ALS and progressive muscular atrophy (PMA) are also indistinguishable.

Some countries simply classify PLS and PMA as ALS. Due to unclear classification, many epidemiological statistical results vary.

In many cases, there are also clear differences between early-onset and late-onset ALS. For example, a significant number of patients with early-onset disease survive beyond 10 years after diagnosis, and most late-onset patients have a very rapid course of disease, such as Stephen Hillenburg, the creator of SpongeBob SquarePants.

It is difficult to classify ALS because of its complex range of symptoms and pathological conditions, as well as the varying course of disease in different patients. Even among patients of the same age and with the same initial symptoms, the progression of disease and survival time vary widely. Therefore, it is very necessary and urgent to establish a clear ALS classification system. In addition to the UMN and LMN-based impairment types, ALS can also be subdivided into bulbar-onset ALS and spinal-onset ALS.

Currently, there are only two drugs on the market for ALS:

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