Amyotrophic Lateral Sclerosis:- A comprehension of symptoms and the latest advancements in the field of treatment.

Abstract:

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. it primarily impacts the cells responsible for controlling voluntary muscles, causing the motor neurons to gradually degenerate and die. This leads to a loss of muscle control and eventual paralysis. (NINDS) In this article, a clear understanding of the symptoms is defined. The recent developments in the area of treatment are explored. it also highlights how clear knowledge of the symptoms allows for efficient development of treatments.?

Introduction:?

Ongoing studies seek to understand the mechanisms that selectively trigger motor neurons to degenerate in ALS. The goals of the research are to understand the mechanisms involved in the development and progression of ALS, examine the influence of genetics and other potential risk factors, identify biomarkers, and develop effective treatments. ALS symptoms initially cause muscle weakness and atrophy in the upper and lower limbs of the body. This eventually spreads to the rest of the body and reduces the quality of life of the individual.

Subsequently, patients develop a form of dementia over time and experience problems with language and decision making. Most people with ALS die from respiratory failure. (NINDS) The assessment of viable biomarkers helps us track the disease progression, which refines therapeutic trial design and reducing trial costs. It is crucial to formulate therapies that deal with secondary consequences of malnutrition and respiratory failure, along with slowing disease progression. (Matthew C, et al.)

Symptoms indicating ALS and their progression over time:

The onset of ALS in an individual is a gradual process and it is expressed in various ways in different people. Although there is universal progressive muscle weakness and paralysis, the patients experience different forms of symptom expression and patterns of progression. The most common initial symptom is muscular deterioration leading to gradual loss of strength. Other early symptoms can include abnormal fatigue, slurred speech, muscle cramps and uncontrollable periods of laughing or crying.

This is caused as the motor neurons degenerate and die, causing muscular atrophy. (ALS association) In about 25%-30% of cases there is a bulbar onset of the disease. This presents with difficulty in chewing and swallowing food (dysphagia), problem in speaking or forming words (dysarthria), reduced respiratory rate (dyspnea), malnourishment, muscle cramps and neuropathy. There is a large variability in the age and site of the onset. The disease is relentlessly progressive. 30%-40% of patients have mild behavioral and cognitive changes. This is consequence of degeneration of frontal and anterior temporal lobes. As the disease spread to the lung muscles, the patients struggle and die from respiratory failure.

Upper limb onset is most commonly in the dominant hand, with thenar muscles being more affected than hypothenar muscles with early involvement of the first interosseous muscle and finger extensors more affected than finger flexors. In the lower limb the anterior tibial muscle is typically affected earlier in the disease course than the gastrocnemius muscle, the hamstrings before the quadriceps muscles. (Masrori and Damme, pp.1922)

Recent advancements in the area of treatment of ALS:

Researchers have puzzled over an effective and efficient treatment for ALS, for over 40 years. This was due to the variability in the symptoms and their progression among different patients. This highlights the complexity of the disease. Proper disease management is ensured by multidisciplinary care, which is accepted positively by the patient and gives a good outcome.

Various pharmacological and non-pharmacological approaches have managed to tackle with the discomforting symptoms. One form of therapy under investigation is masitinib ,an oral tyrosine kinase inhibitor. A randomized controlled trial using 4.5 mg/kg/day of masitinib as an add-on therapy to riluzole suggested a positive effect on the decline of ALS, at least in patients with a typical disease progression. (Masrori and Damme, pp.1926)

The excitotoxic effects have been hypothesized to play an important role in motor neuron degeneration. The inhibitor of presynaptic glutamate release has shown promise in trials and is being further explored.

The use of antisense oligonucleotides and small inhibitory RNA molecules to lower concentrations of mutant messenger RNA slowed disease progression and extended life expectancy. Cell-based therapies for the treatment of neurodegenerative diseases continue to be a growing source of attention and hope worldwide. (Zinman and Cudkowicz)

Conclusion:

Amyotrophic Lateral Sclerosis is a neurodegenerative disease that causes the degradation of motor neurons in the upper limbs and lower limbs. Due to the extensive and variable range of symptoms displayed, it is a complex task for the researchers to find an uniform and efficient treatment. An in-depth knowledge of the symptoms helps in effectively tackling the treatment process. It helps identify the areas of focus and proper identification of biomarkers facilitates the process.

A few significant upstream pathways that may contribute to the death of motor neurons have been identified due to developments in genetics and molecular biology. There are numerous chemicals being produced that are aimed at these possible targets, and human studies are ongoing. Multidisciplinary ALS treatments have been developed in recent years, which has considerably improved clinical care and increased patient survival and quality of life.?

Citations:

“Amyotrophic Lateral Sclerosis (ALS).” National Institute of Neurological Disorders and Stroke (NINDS) https://rb.gy/fqt2a

“Amyotrophic lateral Sclerosis”. The Lancet. Volume 377, Issue 9769, 12–18 March 2011, Pages 942- 955. Matthew C Kiernan, Steve Vucic, Benjamin C Cheah, Martin R Turner, Andrew Eisen, Orla Hardiman, James R Burrell, Margaret C Zoing. https://www.sciencedirect.com/science/article/pii/S0140673610611567

“ALS Symptoms and Diagnosis”. ALS Association, https://www.als.org/understanding-als/symptoms-diagnosis

“Amyotrophic Lateral Sclerosis: a clinical review”. Wiley Online Library. P. Masrori and P. Van Damme. Department of Neurosciences, Experimental Neurology, KU Leuven–University of Leuven, Leuven; Laboratory of Neurobiology, Center for Brain and Disease Research, VIB, Leuven; and Department of Neurology, University Hospitals Leuven, Leuven, Belgium. https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.14393

“Emerging targets and treatments in amyotrophic lateral sclerosis”. The Lancet. Volume 10, Issue 5, May 2011, Pages 481-490. Dr Lorne Zinman and Prof. Merit Cudkowicz https://www.sciencedirect.com/science/article/abs/pii/S1474442211700242

This article was written by Sheiza Habib under our editorial head Tanvi Duarah