The degeneration of brain cells that occurs in Parkinson’s disease can be caused by either externally provoked cell death or internally initiated suicide when the molecule that normally prevents these fatal alternatives is missing, according to results of studies in mouse models by St. Jude investigators.

In Parkinson’s disease, nerve cells in the part of the brain called the substantia nigra die, resulting in the loss of dopamine, a nerve-signaling molecule that helps control muscle movement. The absence of dopamine from these cells, called dopaminergic neurons, causes a loss of muscle control, trembling and lack of coordination.

The molecule that prevents damage to the substantia nigra is an enzyme called GST pi (“pie”) that stands like a sentry at the crossroads of several biochemical pathways, any one of which can lead to Parkinson’s disease, the researchers reported in an article that appears in the February 1 early online edition of Proceedings of the National Academy of Sciences.

The job of the antioxidant GST pi is to protect the cell from death caused by either environmental toxins (externally evoked cell death), such as herbicides and pesticides, or a self-destruction process called apoptosis (“suicide”), triggered by certain stressful conditions in the cell. If GST pi levels are reduced or this enzyme is overwhelmed by toxins, the dopaminergic neurons are at an increased risk of death.

The finding that GST pi plays a key role in preventing Parkinson’s suggests that measuring levels of this enzyme might be an effective way to determine individuals at risk for developing this disease, according to Richard Smeyne, PhD, Developmental Neurobiology. “And in the future, treatments that increase GST pi levels in the substantia nigra might help to prevent or delay the onset of Parkinson’s disease or reduce its severity,” said Smeyne, the report’s senior author.

The study sheds light on the cause of most cases of Parkinson’s disease, which currently are unexplained.

“The majority of these cases of Parkinson’s disease appear to arise because individuals who have a genetic susceptibility to the disease are exposed to environmental toxins such as pesticides and herbicides, which trigger the formation of free radicals that kill dopaminergic neurons in the substantia nigra,” Smeyne said. “We also know that GST pi blocks the process of cell suicide triggered by stresses that the cell can’t overcome, such as an increase in the presence of free radicals or a loss of the cell’s ability to produce energy.

Michelle Smeyne, Developmental Neurobiology, and former employees Justin Boyd and Kennie Raviie Shepherd did most of the work on this project; other St. Jude authors include Yun Jiao, MD, and former employees Brooks Barnes Pond and Matthew Hatler.

Source

The test will lead to earlier diagnosis and more effective treatments for patients with the neurological disorder.

Most patients are diagnosed by observing symptoms such as tremors, slow movement and muscular stiffness.

Because of the slow onset of the disease, many sufferers in the early stages are misdiagnosed as having other conditions such as repeated strokes.

This can lead to the use of inappropriate treatments that fail to slow the progression of the disease.

The research, which was funded by the actor Michael J Fox – who was diagnosed with Parkinson’s in 1991 at the age of 30 – suggests that genetic alterations caused by the condition can be detected by chemical changes in the blood.

Dr Erik Christensen, the chief executive of DiaGenic, a Norwegian life sciences company that developed the test, said: “Progression of Parkinson’s disease has a serious impact on the quality of life of sufferers. The earlier an accurate diagnosis can be made, the earlier treatment can start and the better the prognosis for the patient.”

Researchers at DiaGenic announced last year that they had used the same process to develop a blood test that is sensitive enough to pick up early symptoms of Alzheimer’s disease.

As part of this work they also discovered 500 genes that are affected by Parkinson’s which trigger chemical changes that can also be identified in blood samples.

Dr Clemens Scherzer of the Brigham and Women’s Hospital in Boston, Massachusetts, will test DiaGenic’s preliminary findings using blood samples already collected from 300 patients.

Dr Christensen said that he expected to be able to apply for a licence so that doctors could use the test by the end of next year.

There are some 10,000 new cases of Parkinson’s diagnosed every year in Britain, and about 120,000 people live with the condition, which occurs when cells in the part of the brain that controls movement die.

Dr Kieran Breen, of the Parkinson’s Disease Society, said: “The diagnosis of Parkinson’s can be difficult, given it has a slow onset and can be mistaken for a number of other conditions, particularly in the early stages.

“There is, therefore, a great need to look for something to measure in the body associated with Parkinson’s to be able to develop a test for its diagnosis.

“As blood samples have already been collected, the US researchers can immediately start work on analysing these samples. We look forward to the results.”

Last week Opaldia, which provides private health care in Britain, announced that it is expecting to begin offering a blood test to detect breast cancer, also developed by DiaGenic, to its members next year.

Source: http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2007/12/22/nhealth122.xml

Dec 09, 2007 04:30 AM

Brett Popplewell
Staff Reporter
Friends, family and fans of the late Norval Morrisseau gathered last night to pay tribute to the Canadian artist who took native art and put it on the world stage in vibrant colour.

In a small auditorium in downtown Toronto, native elder Vern Harper and others who knew Morrisseau from his days as an artist living hand-to-mouth on the streets of Toronto spoke of the man heralded as “the Picasso of the North” as a spirited individual, well loved by all who knew him.

“Everyone recognized him as a great artist, but he was more than that. He was a great shaman. There won’t be one like him in a thousand years,” said Harper. “Just being in his presence when he was at his best or at his worst was a great honour.”

Morrisseau, 75, died Tuesday at Toronto General Hospital after a long battle with Parkinson’s disease. Harper, a long-time friend of Morrisseau, was joined by two artists who had been mentored by the experienced painter.

One of those artists, RitchieSinclair, said it’s unfair for the media to “lift him up here and they put him down there,” in reference to Morrisseau’s reputation as the most influential native artist of his generation, as well as a troubled alcoholic.

Sinclair and fellow painter Brian Marion vowed last night to honour Morrisseau by starting a native school of art in his memory.

They hope to incorporate Morrisseau’s native name, “Miskwaabik Animiki,” which translates to Copper Thunderbird, into the school’s name.

“From an artist’s perspective, (his legacy) is just starting now,” Sinclair said. “All of us will be long gone and what he did is just going to keep growing.”

The traditional memorial featured native dance, singing, the smoking of a prayer pipe and managed, for the most part, to avoid the recent controversy over what should come of Morrisseau’s remains.

Christian Morrisseau, the artist’s youngest son and one of his seven children, insists his father’s remains should be brought back to a reserve near Thunder Bay where the artist’s estranged wife is buried.

Meanwhile the artist’s brother wants his ashes to be spread over Lake Nipigon.

What exactly his wishes were remain open to interpretations.

“Norval always knew that this was not his home and that he would go home sometime and now he’s going home,” said Harper.

Regardless of the controversy, Christian affirmed yesterday that his love for his father is “unconditional.”

“I have to say although he really wasn’t there for me as I grew up, I’ve learned who my father was through books, through my sister and through my mother as well,” he said.