Paralysis Island – Machado-Joseph Disease 

By  Staff Writer

Groote Eylandt, in the Northern Territory of Australia is home to stunning beaches and the highest prevalence of Machado-Joseph genetic disease in the world. Five per cent of its residents are at risk of or suffer from Machado-Joseph Disease. It is named after two men (“William Machado” and “Antone Joseph”) who were the patriarchs of the families in which the condition was initially described.MJD occurs when a fault in a chromosome causes nerve cells in the brain to die prematurely. It is similar to Huntington’s and Motor Neuron diseases. Close to 70 per cent of people with MJD have clinical depression, according to the MJD Foundation. Machado-Joseph disease (MJD)—also called spinocerebellar ataxia Type 3 (SCA3)—is one of approximately 30 recognized, dominantly inherited forms of ataxia. Ataxia is a general term meaning lack of muscle control or coordination. MJD is characterized by slowly progressive clumsiness in the arms and legs, a staggering lurching gait that can be mistaken for drunkenness, difficulty with speech and swallowing, impaired eye movements sometimes accompanied by double vision or bulging eyes, and lower limb spasticity.

From News.com.au “More people on the island than ever before are “symptomatic” of the deadly rare genetic disorder with sufferers getting younger and the gene getting stronger, according to MJD Foundation chief executive Nadia Lindop.
The NT has the highest concentration and “most severe” strain of MJD in the world with an estimated 654 residents — mostly on Groote Eylandt — officially “at risk” and more than 100 currently “symptomatic”. There is no known cure.
MJD is a debilitating and deadly hereditary neurodegenerative condition that starts with muscle weakness then progresses to a total lack of voluntary control and significant permanent physical disability.
In the late stages of MJD, the sufferer cannot move or talk but remains fully alert — a state often referred to as ‘locked in syndrome’. Ms Lindop told news.com.au it was a “cruel disease” that “doesn’t affect cognitive function so the person suffering from it is completely aware of everything that is happening to them … even when they can no longer move or speak”.
“Their brains are fine … that’s the very cruel part of the disease,” she said.
“The disease gives the person urinary incontinence, slurred speech, affects swallowing, mobility and anything you need muscles for.

“In the end people are locked into their bodies.”

One unusual feature of MJD and many other expanded repeat diseases is a phenomenon called anticipation. Anticipation is the remarkable fact that children of affected parents tend to develop symptoms of the disease earlier in life and may experience more severe symptoms. This is due to the tendency for the expanded repeat mutation to further expand when being passed to the next generation, especially when passed from the father. Because longer expansions tend to cause earlier and more severe disease, this molecular growth from one generation to the next likewise causes, on average, an earlier age of onset in subsequent generations.

Machado-Joseph Disease A Search For A Cure

“Earlier this year, Australian neuroscientists at Macquarie University’s faculty of Medicine and Health Sciences in Sydney, started a research program involving zebrafish in a bid to slow the progression of MJD.
The tropical freshwater fish shares 70 per cent of the same genes as humans.
Zebrafish embryos were injected with the mutant human gene that causes MJD before different drugs were tested on them to see if they would cause them to “move and swim better”.
“Zebrafish are transparent during development and they can absorb drugs that we add to their water, allowing us to treat large numbers of zebrafish to explore the effects of drugs,” lead researcher Dr Angela Laird said.
Traditional owners on Groote Eylandt got the zebrafish project off the ground, with the Anindilyakwa Land Council donating $1 million for medical research to the MJD Foundation.
Ms Lindop said researchers found positive results they are “close to publishing”.
“If that drugs works it won’t cure the disease,” she said.
“Sufferers will still have the genetic fault to pass on but it will slow down the progression of MJD”.” MJD is incurable, but some symptoms of the disease can be treated. Levodopa therapy (used in treating individuals with Parkinson’s disease) can ease parkinsonian features (stiffness and slowness of movments, often accompanied by a tremor) for many years. Antispasmodic drugs, such as baclofen, can help reduce spasticity. Botulinum toxin can treat severe spasticity and some symptoms of dystonia, but it should be used as a last resort due to possible side effects, such as swallowing problems (dysphagia). Speech problems (dysarthria) and dysphagia can be treated with medication and speech therapy. Wearing prism glasses can reduce blurred or double vision, but eye surgery has only short-term benefits due to the progressive degeneration of eye muscles.

Machado-Joseph Disease – DNA Carrier Testing

A definitive diagnosis of MJD can be made only with a genetic test. The genetic test for MJD (SCA3) is highly accurate. The direct detection of the genetic mutation responsible for MJD has been available since 1995. Genetic testing looks at the number of CAG repeats within the coding region of the MJD/ATXN3 gene on chromosome 14. The DNA test will prove positive for MJD if this region contains 61-87 repeats, as opposed to the 12-44 repeats found in healthy individuals. A limitation to this test is that if the number of CAG repeats in an individual being tested falls between the healthy and pathogenic ranges (45-60 repeats), however the test cannot predict whether an individual will have MJD symptoms. Those individuals who are at risk for MJD (i.e. have an affected parent) but do not have any symptoms can undergo presymptomatic testing to determine whether they carry the disease allele (and thus will later develop the disease). Obtaining presymptomatic testing is a highly personal decision that at-risk people should make only after completely considering the potential pros and cons. Many at-risk individuals choose not to undergo the DNA test out of concern for job discrimination and difficulty in obtaining or maintaining insurance, among other reasons. If someone in your family has been diagnosed with Machado-Joseph disease you should consider a DNA carrier test.

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