Motor Neuron Disease: Types, Symptoms, and Emerging Therapies

Motor neuron disease frequently leads to paralysis and respiratory failure, resulting in a short life span. Among its many subtypes, amyotrophic lateral sclerosis is the most predominant, showing a maximum survival period of only 3 years. Scientists are exploring the pathology of the disorder to develop effective therapeutic treatments. They have also ventured into regenerative therapies for better treatment outcomes.

Motor Neuron Disease

Motor neuron disease (MND) is a group of progressive neurological diseases. It causes gradual deterioration of nerve cells in the spinal cord or brainstem. The group exhibits involvement of either upper or lower motor neurons or both. Upper motor neurons originate in the brain and travel towards either the brainstem or the spinal cord. Lower motor neurons travel from the spinal cord to different muscles and tissues in the body. They include both voluntary and involuntary muscle movements. The symptoms manifest as wasting of muscles, emotional deregulation, behavioral changes, and cognitive impairments.

Motor Neuron Diseases Types

MND has been classified into different categories based on site of origin and severity.

Amyotrophic Lateral Sclerosis (ALS): It is the most prominent form of MND. Based on Lou Gehrig, a famous baseball player, the disease is also referred to as Lou Gehrig’s disease. It involves both upper and lower motor neurons. The symptoms include a gradual loss of voluntary muscles, evident by muscle stiffness, weakness, spasms, etc. The disease progresses to impact the ability to talk, eat, and even breathe.

Progressive Bulbar Palsy: It also affects the upper and lower motor neurons but originates from the bulbar region. It causes difficulty in speech and swallowing. It does not have a severe impact on limbs, only leading to muscle weakness.

Progressive Muscular Atrophy: It only damages lower motor neurons, affecting only a small group of people, primarily in the higher age group. The symptoms manifest as wasting of muscles along with weakness. The involvement of the bulbar region happens in later stages. Therefore, the survival period in this type of Motor Neuron Diseases is relatively higher.

Primary Lateral Sclerosis: It affects upper motor neurons, leading to muscle wasting in lower limbs, which gradually spreads to arms and other muscles. It does not decrease the life span of an individual and only results in difficulty in walking, which eventually progresses to difficulties in speaking, breathing, and chewing.

Additional classification of MND depends on their underlying cause, which could be genetic (known as familial) or sporadic (non-hereditary, such as environmental and lifestyle habits). As the respiratory functions begin to decline, the survival period diminishes. It is especially evident in ALS, which has a maximum survival time of 3 years.

Does ALS cause memory loss?

Changes in behavior and cognitive skills are well-documented in ALS. It is imperative to know the spectrum of the changes to aid not just the patient but also their families in managing the disease progression. ALS also impairs executive functions, which include an individual’s ability to plan, organize, reason, regulate emotions, etc. Recent studies have investigated the memory problems in ALS patients. They have seen key features overlap with those of dementia. Studies have then evaluated and stated that memory deficits are present in ALS patients, particularly in terms of recognition.

Current Treatment Modalities

The pathogenesis of ALS includes several pathways, such as the abnormal distribution of proteins in cellular compartments, oxidative stress, mitochondria dysfunction, inflammation, aberrant vesicle transport, neurotoxicity, RNA processing, etc., in nerve cells. It eventually leads to nerve cell death. Even the non-nerve cells, such as glial cells, astrocytes, immune cells, and oligodendrocytes, contribute to this process. This multifactorial nature of the problem has impeded the discovery of suitable therapeutic candidates for drug development. The available treatment only targets one pathway instead of a holistic-level approach. For example, edaravone acts on oxidative stress, and riluzole manages nerve transmission for treating ALS.

Stem Cell Treatment

The low survival period and lack of effective treatment have directed the scientific community to seek a cure in the regenerative field. Stem cells are known to differentiate into neurons and also possess many unique properties that can reduce neural loss. Therefore, clinical trials have been investigating the effects of  Stem Cell Treatment on ALS patients. It can act on oxidative stress, the immune system, inflammation, and various other aspects of the disorder. In animal models, the therapy has shown prolonged survival periods, improved neurological scores, decreased neuronal loss, and decreased inflammation. In humans, mesenchymal stem cells have demonstrated a delay in disease progression, reduced inflammation, and improvements in biomarkers of inflammation and neuronal loss without any adverse reactions.

Conclusion

The effects of MND expand from deficits in motor skills to difficulty in executive functions. Patients with ALS have impaired emotional regulation and reasoning, as well as memory problems. Multiple pathways are involved in the pathology, requiring a treatment that can provide holistic-level effects. Current treatments lack multi-level effects, lowering their success in treating the disorder effectively. On the other hand, stem cell therapies are emerging with their potential for regeneration. Mesenchymal stem cells have shown distinct properties that assist them in combating different pathways of the disease. Clinical trials have shown favorable outcomes without any safety issues. However, the therapy still requires standardization in terms of sources of stem cells, administration route, and dosage. Advancells has been contributing to the progress of  Stem Cell Therapy by providing premium-quality stem cells.