Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord.

ALS is also known as Lou Gehrig's disease after the famous baseball player who died from this condition.

Motor neurons are nerve cells that control muscle movement. Upper motor neurons send messages from the brain to the spinal cord, and lower motor neurons send messages from the spinal cord to the muscles allowing movement. Motor neurons are an important part of the body's neuromuscular system.

Etymologically:

Amyotrophic- lack of muscle nourishment

Lateral- portion of the spinal cord where motor neuron damage occurs

Sclerosis- neuronal degeneration causes scarring and hardening of tissue.

As a result of neurons degenerating this condition leads to muscle weakening, twitching, and an inability to move the arms, legs, and body. Hence a debilitating disease. When the muscles in the chest area stop working, it becomes hard or impossible to breathe on one's own.

ALS does not affect the senses (sight, smell, taste, hearing, touch). And it only rarely affects bladder or bowel function, or a person's ability to think or reason.

The cause

For patients without a family history of the disease, which includes -95% of cases, there is no known cause for ALS. There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families, although this accounts for only around 5% of all cases. An inherited genetic defect on chromosome 21 (coding for superoxide dismutase) is associated with approximately 20% of familial cases of ALS.This mutation is believed to be autosomal dominant. 

Treatment: There is no known cure for ALS. The first drug treatment for the disease is a medicine called riluzole. Riluzole slows the disease progression and prolongs life.Treatments to control symptoms are also helpful:

• Baclofen or diazepam may be used to control spasticity that interferes with daily activities.

• Trihexyphenidyl or amitriptyline may be prescribed for people with problems swallowing their own saliva.

Physical therapy, rehabilitation, use of braces or a wheelchair, or other orthopedic measures may be needed to maximize muscle function and general health.

Choking is common. Patients may decide to have a tube placed into their stomach for feeding, called a gastrostomy.

A nutritionist is very important. Patients with ALS tend to lose weight. The illness itself increases the need for food and calories. At the same time, problems with swallowing make it hard to eat enough.

Breathing devices include machines that are used only at night, and constant mechanical ventilation.

Support Groups: Emotional support is vital in coping with the disorder, because mental functioning is not affected. Groups such as the ALS Association may be available to help people who are coping with the disorder.

Research 

Scientists are seeking to understand the mechanisms that trigger selective motor neurons to degenerate in ALS and to find effective approaches to halt the processes leading to cell death. 

This work includes studies in animals to identify the means by which SOD1 mutations lead to the destruction of neurons. The excessive accumulation of free radicals, which has been implicated in a number of neurodegenerative diseases including ALS, is also being closely studied. 

In addition, researchers are examining how the loss of neurotrophic factors may be involved in ALS. Neurotrophic factors are chemicals found in the brain and spinal cord that play a vital role in the development, specification, maintenance, and protection of neurons. Researchers hope to find the cause or causes of motor neuron degeneration in ALS and develop therapies to slow the progression of the disease.

Stem Cell Therapy

One of the proposed future therapies for ALS is stem cell therapy, where stem cells harvested from either human bone marrow or preserved umbilical cord blood can be implanted in the patient to replace damaged cells. In a neurodegenerative disease like ALS, cells adjacent to motor neurons in the surrounding area of the body become damaged as well, causing widespread cell death and a rapid decrease in normal functioning in the patient. These stem cells would be directed to the damaged area and provide necessary growth factors to the damaged or dying motor neurons and other cells.

This breakthrough has raised several concerns that could halt the progression of research in this field. the many controversial ethical implications that have followed the stem cell debated for years must be taken into consideration. Although the implantation of the stem cells into the site of damage has been very successful in animal models, there has been little evidence that they connect with their desired targets (motor neurons to muscle fibres). Motor neurons must connect to muscle fibres over distance of up to 3 meters and making this connection is vital to the regeneration of activity. An additional concern in stem cell therapy research is the possibility of immuno-rejection of foreign cells by the body's immune system.

what may have appeared to be impossible several years ago of particular relevance to ALS is whether stem cells can be directed to generate motor neurons. Research in Dr. Tom Jessell's laboratory demonstrates that mouse embryonic stem cells can indeed be differentiated into motor neurons and when introduced into the spinal cord of embryonic chicks, motor axons form contacts with skeletal muscle. This promising research demonstrates the progress that has recently been made. Scientists acknowledge that the leap from an embryonic chick to a human adult is huge and currently an unobtainable goal. However, the promise of stem cells as vehicles for trophic support for dying neurons is possibly a more feasible goal and many studies are focusing on this approach. Several studies have shown that embryonic stem cells in culture can be genetically modified. Using this technology, stem cells can be modified to deliver genes and other factors to dying motor neurons. More research is needed in this area.

There are currently no human clinical trials however a few unpublished efforts have been disclosed using bone marrow and cord blood stem cells in humans and are in very early stages. With all the excitement and possibilities stem cells have to offer as a therapy, it is critical that scientists  and clinicians are cautious and plan rigorous studies. If ethical concerns can be properly addressed and continued research regarding the innervation of nerve projections sees progress, a human-model clinical trial can take place in the near future.