Diseases

About ALS

About Parkinsons

ALS is a neurodegenerative disorder characterized by the progressive loss of motor neurons. Motor neuron loss compromises the ability to initiate and control muscle movement, and people with ALS experience progressive muscle weakness and wasting, followed by paralysis. They may also experience dysphagia and respiratory difficulties, among other problems. Muscle wasting occurs in the extremities, and tends to move from distal muscles to proximal ones. Affected muscles of note include those between the ribs, and the diaphragm. Dysphagia and dysarthria occur as motor neurons in the brain stem deteriorate. Diaphragmatic involvement is responsible for respiratory insufficiency. This last problem generally occurs in the later stages of the disease, and patients must eventually use respirators in order to survive. Importantly, most ALS patients do not experience loss of intelligence or loss of awareness of their surroundings.

Average survival in ALS is 3 – 5 years from date of diagnosis. Loss of function and resulting debilitation can occur rapidly, esulting in rapid loss of quality of life. People with ALS lose their ability to walk, use their hands, eat and speak, and eventually become dependent on respirators. The situation puts considerable strain on patients and their families and friends, and a treatment for the disease is urgently needed.

In rare cases, symptoms may progress to a certain point and stop. Stephen Hawking is a well-known person whose ALS stopped progressing. Even rarer still, the condition of an ALS patient may also improve spontaneously.
Unfortunately, at this time, the therapeutic options for ALS patients are severely limited. Rilutek, the sole FDA-approved medication for ALS, extends the survival of patients by only 2 – 3 months, making it only marginally effective at best. Although drugs such as Baclofen are useful for treating severe muscle spasticity, they do not extend life, and other approaches to managing ALS are mainly supportive. They include techniques of assisted ventilation and physical therapy.

There are three types of ALS:

• Sporadic

• Familial

• Western Pacific ALS with or without Parkinsonism-dementia (ALS/P-D), which occurs on the islands of Guam, Honshu, and Irian Jaya.

Sporadic

Sporadic ALS occurs in people with no family history of ALS. It is by far the most common form of ALS, and affects roughly 90% of current patients. Sporadic ALS follows the course outlined above.
Unfortunately, its cause or causes are not known at this time. Many ideas about factors involved in the development of ALS have been proposed. They include, but are not limited to, glutamate toxicity, which can contribute to the death of motor neurons, irregularities in the immune responses in injured neurons, which can also contribute to their deaths and dysfunctions, mitochondrial abnormalities, infectious agents, and environmental factors.

Familial

Familial ALS affects roughly 10% of ALS patients. The clinical courses of familial and sporadic ALS are essentially the same. Although not all genes that are involved in familial ALS have been identified, one of them, SOD1 was discovered in the 1990s.

The discovery of SOD1’s involvement in ALS led to the creation of mouse and, more recently, rat animal models of ALS. For example, the ALS rats to be used in this study carry hemizygous mutations in SOD1. They harbor one normal copy of the SOD1 gene and one mutant copy of it. The mutant copy has a gain of function mutation, which causes the protein made by the mutant allele to gain a function it previously did not have. In the case of ALS, mutant SOD1 seems to gain a function in generating free radicals, but the mechanism by which this process causes the disease is still not known.

Western Pacific ALS with Parkinsonism and/or dementia

This form of ALS is often coupled with Parkinsonian symptoms and dementia. On Guam, the ALS-like disorder is called lytico, while the PD-like disorder is called bodig. The spectrum of disease on Guam shows high variability, with many people showing signs of both lytico and bodig. On Irian Jaya, both forms appear to be called lumpu.1

On Guam, Lytico occurs at high levels in Chamorro people born before 1952, but not in people born after this time. It has also been documented in Chamorro people who had been away from Guam for two decades or more. It has also been seen in non-native residents residing in Chamorro villages. Overall, its course is similar to that of familial or sporadic ALS.

In 2003, after 50 years of intensive research into the causes of lytico, researchers led by Dr. Paul Cox discovered that lytico and bodig appear to be caused by the consumption of Guamian flying fox bats.2,3 The bats, which were hunted to extinction on the island, harbored BMAA (B-methylamino-L-alanine), a neurotoxin that is produced by cyanobacteria living as symbionts in the roots of cycad trees. The toxin is biomagnified by a factor of 100 as it moves from cyanobacteria to parts of cycad trees that were consumed by flying foxes. It was biomagnified by a further factor of 100 in the flying foxes, which were eaten by the Chamorros. The easy availability of guns on the island during and after the war allowed the Chamorros to hunt the bats more easily, which caused the demise of the bats. Their demise, in turn, provides an explanation for why the disease does not appear in people born after 1952. Although the theory has not been fully proven, it is a provocative explanation for the development of lytico-bodig.

Although the causes for lumpu are less well-understood, they may be related to the use of cycad-based poultices on open wounds on Irian Jaya. Pastes made from cycad seeds have been used by two groups of local people in the western part of Irian Jaya and applied directly on top of open skin wounds or even packed into them. Their use has declined in recent decades, as has the incidence of lumpu. Although evidence implicating medicinal use of cycad seeds is not definitive in this case, it remains a provocative theory.

1 Spencer PSS, Palmer VS & Ludilph AC (2005) On the decline and etiology of high-incidence motor system disease in West Papua (Southwest New Guinea). Movement Disorders 20(supp 12): S119 – s126.

2 Cox PA, Murch SJ & Banack SA (2003) Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proc Natl Acad Sci U S A. 100(23): 13380 – 13383.

3 Murch SJ, Cox PA & Banack SA (2004) A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam. Proc Natl Acad Sci U S A. 101(33): 12228 – 12231.