New Protein May Reverse Neurodegenerative Diseases

Newswise — An investigational protein that transformed normal laboratory mice into super-jocks holds great promise in developing new treatments for neurodegenerative diseases like Parkinson’s, Alzheimer’s and ALS (Lou Gehrig’s Disease), say researchers at the University of Virginia Health System.

A study published in the February 17, 2009 online edition of Mitochondrion reports that the protein, rhTFAM (an abbreviation for recombinant-human mitochondrial transcription factor A), succeeded in entering and energizing the DNA of the mice’s mitochondria, enabling them to run two times longer on their rotating rods than a control group cohort.

Because many neurodegenerative diseases cause mitochondria to malfunction, medical researchers have been focusing on developing methods for repairing and restoring them. The new UVA study represents an important step toward achieving that goal. It shows that a naturally occurring protein, TFAM, can be engineered to rapidly pass through cell membranes and target mitochondria. Study findings show that rhTFAM acts on cultured cells carrying a mitochondrial DNA disease as well as lab mice.

Conducted in conjunction with Gencia Corporation, a Charlottesville-based biotechnology firm that owns rhTFAM, the study also describes a scalable method of producing the protein in needed quantities.

Mitochondria are the cellular engines that transform food into fuel in our bodies and perform their work in the energy-intensive tissue of our brains, retinas, hearts and skeletal muscles. When damaged, mitochondria slow down, stop generating energy effectively and begin to over-produce oxygen free radicals. If produced in excess, oxygen free radicals chemically attack all cell components, including proteins, DNA and lipids in cell membranes.

“In simple terms, an overabundance of these free radicals cause cells to start rusting,” notes lead study author James P. Bennett, Jr., M.D., PhD, a professor of neurology and psychiatric research at the UVA School of Medicine and director of its Center for the Study of Neurodegenerative Diseases.

While the UVA findings are preliminary, Bennett considers them encouraging. “We’ve shown that the human mitochondrial genome can be manipulated from outside the cell to change expression and increase mitochondrial energy production,” he notes. “This is arguably the most essential physiological role of the mitochondria.”

Although important questions remain about the technology, mechanisms and therapeutic potential of rhTFAM, Bennett believes his team’s findings could contribute to the development of treatments that repair and restore damaged mitochondria in cells. “We’re looking toward the day when we can reverse or delay the progression of various neurodegenerative diseases and other conditions where cell energy production is deficient, including cancer, diabetes and aging,” he says.

Gencia made rhTFAM available to UVA under a material transfer agreement. One study author, Francisco R. Portell, has an affiliation with the company.

Study authors also include Shilpa Iyer, Ravindar R. Thomas, Lisa D. Dunham and Caitlin K. Quigley. All work at the Center for the Study of Neurodegenerative Diseases and the Morris K. Udall Parkinson’s Disease Research Center of Excellence at UVA.

Cancer link to Parkinson's - study

Press Association, February 16, 2009

People with a family history of skin cancer may be more vulnerable to Parkinson's disease, new research suggests.

A link between melanoma and Parkinson's was already suspected. Previous studies have shown that sufferers of Parkinson's disease have an increased risk of developing the cancer.

The new study showed individuals who had a family history of melanoma were nearly twice as likely to develop Parkinson's as those who did not.

Scientists looked at almost 157,000 people who had not shown any symptoms of Parkinson's. They were asked if any of their parents or siblings had been diagnosed with melanoma, a type of tumour that includes the deadliest form of skin cancer.

Researchers then traced their progress for a period of 14 to 20 years. During that time, 616 of the group were diagnosed with Parkinson's disease.

The findings will be presented at the American Academy of Neurology's 61st annual meeting in Seattle in the spring.

Study author Dr Xiang Gao, from Harvard University School of Public Health in Boston, said: "The results from this study suggest that melanoma and Parkinson's could share common genetic components. More research needs to be done to examine the relationship between these two diseases."

Parkinson's disease is characterised by muscle rigidity and tremors and affects about 10,000 people in the UK each year.

It is caused by the loss of brain cells that help co-ordinate movement.

An estimated 9,300 people in the UK are diagnosed with melanoma each year. The disease is curable if caught early but malignant melanoma can be highly dangerous.

New Evidence Melanoma & Parkinson’s Link

Valentina Wilson / NBC33 News

February 16, 2009 - 7:24pm

New evidence links melanoma to Parkinson’s Disease. Harvard researchers studied more than 150,000 people for nearly 20 years. They found those with a reported family history of melanoma were nearly twice as likely to develop Parkinson’s. This suggests there could be a common gene between the two diseases. Melanoma is the deadliest form of skin cancer.

Scientists Heartened at Prospect of End to Stem Cell Ban

Move by Obama expected to kick-start efforts to unlock therapeutic potential

Posted February 9, 2009

By Amanda Gardner
HealthDay Reporter

MONDAY, Feb. 9 (HealthDay News) -- Researchers are rejoicing over President Barack Obama's anticipated lifting of the eight-year ban on embryonic stem cell research imposed by his predecessor, President George W. Bush.

The anticipation moved one step closer to reality Thursday, with media reports that Obama gave House Democrats at a closed-door Virginia retreat a "guarantee" that he would sign an executive order overturning Bush's policy.

"It's going to remove an embarrassment for American science," said Dr. Darwin Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White Hospital in Temple. "It's a statement that we're going to again believe in science."

Yet those same experts are aware that the sobering state of the economy could impose its own restrictions on this type of research.

"This clearly is a very important part of our medical future," said Paul Sanberg, distinguished professor of neurosurgery and director of the University of South Florida Center of Excellence for Aging and Brain Repair in Tampa. "[But] to clear the path for this without giving additional money to the National Institutes of Health will be disappointing. I hope the stimulus package also includes an increase in embryonic stem cell funding."

Sanberg also expressed concern that any monies redirected to stem cell research could divert funds from other critical avenues of research. "If it's a normal competitive process, it will take money away from other programs," he said.

Stem cell research received a big boost in January, when the U.S. Food and Drug Administration approved the first-ever human trial using embryonic stem cells as a medical treatment.

Geron Corp., a California-based biotech company, was given the OK to implant embryonic stem cells in eight to 10 paraplegic patients who can use their arms but can't walk.

In 2001, then-president Bush limited federal funding for stem cell research only to human embryonic stem cell lines that already existed.

The decision prompted some scientists to worry that the United States would fall behind other countries in the drive to unlock the potential of stem cell research.

Embryonic stem cells are the most basic human cells, believed to be capable of growing into any type of cell in the body. Working as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells. The scientific hope is that stem cells may, at some point in the future, become capable of treating a variety of diseases and conditions, such as Parkinson's disease, diabetes, heart disease and spinal cord injuries, according to the U.S. National Institutes of Health.

National polls continue to find that the majority of Americans favors embryonic stem cell research, although some surveys have found that that support has declined somewhat in recent years.

Many people object to the use of embryonic stem cells, contending that the research requires the destruction of potential life, because the cells must be extracted from human embryos.

The stem cells being used in the recently approved Geron trial were obtained from one of the Bush administration's approved stem cell lines. And no federal funds were used in the development of this treatment.

Since the restrictions on embryonic stem cell research took effect, many research institutions have redirected their focus to other types of stem cells. Prockop's institution, for instance, deals only with adult stem cells.

Adult stem cells can give rise to all the specialized types of cells found in tissue from which they originated, such as skin. But, scientists don't agree on whether adult stem cells may yield cell types other than those of the tissue from which they originate, according to the National Institutes of Health.

Prockop said embryonic stem cells "are mainly of interest as a research tool and a biological experimental system. Their use in patients in spite of that recent approval for Geron is really very questionable because of the potential for tumors."

Still, the anticipated lessening of restrictions by the Obama administration may help funnel more private money into stem cell research, the experts said.

"This should give more general acceptance to stem cell research, because now, there won't be this stigma associated with it as much," Sanberg said.

And, perhaps, a new federal policy would spur organizations such as the American Heart Association -- which currently does not fund research involving human embryonic stem cells or stem cells derived from fetal tissue -- to channel funds into this line of research, Sanberg added. (The heart association said it "recognizes the value of all types of stem cell research and supports federal funding of this research.")

Still, Sanberg pointed out, some ethical issues surrounding stem cell research and its application will remain.

For instance, he said, "There still needs to be some oversight on the uses of stem cells and cloning."

More information

To learn more about stem cells, visit the U.S. National Institutes of Health.

Link found between genetic and environmental causes of Parkinson's disease

Published: Wednesday, 4-Feb-2009

Medical Research News Scientists at the Whitehead Institute for Biomedical Research have found that a single gene, known as PARK9, protects cells from manganese toxicity and rescues neurons from over-expression of the protein alpha-synuclein. Misfolded alpha-synuclein is the hallmark of Parkinson's disease. "This is one of the first connections between Parkinson's disease genetics and the environment," says Aaron Gitler, one of the co-authors of a paper published online in the February 1 edition of Nature Genetics. Parkinson's disease is a neurodegenerative disorder characterized by tremors, muscle rigidity, and slowed movements. In the neural cells of Parkinson's patients' brains, researchers have noted Lewy bodies, abnormal spheres composed of the protein alpha-synuclein. There is currently no cure for the disease, and current Parkinson's therapies only address disease symptoms. "Using yeast to study Parkinson's means that we will be able to start understanding the underlying pathobiology of the disease and eventually design rational therapeutic strategies based on what's causing the disease rather than what's the outcome," says Whitehead Member Susan Lindquist. "In other words, treating the root cause rather than the symptoms." The specific causes of the disease remain unknown. Growing evidence in the research and medical communities implicates baffling and disconnected genetic and environmental factors. One genetic factor seems to be alpha-synuclein overexpression, which can be caused by too many copies of its gene. Another is mutations in a gene of previously unknown function PARK9. And overexposure to the metal manganese can lead to parkinsonism, a Parkinson's disease-like syndrome. Now researchers in the laboratory of Whitehead Member Susan Lindquist have associated these three factors. "One of the reasons PARK9 is so interesting is when it's mutated, it leads to early onset parkinsonism," says Melissa Geddie, a Lindquist postdoctoral researcher and co-author of the paper. First, Gitler (then in the Lindquist lab) found that wild-type (no mutations) PARK9 suppresses alpha-synuclein toxicity in a yeast model of Parkinson's disease. Gitler, Geddie and University of Pennsylvania postdoctoral fellow Alessandra Chesi then examined the function of the yeast version of the gene, called yeast PARK9 (YPK9). When yeast cells possessing a normal YPK9 gene exposed to various metals were more resistant to manganese than cells lacking the YPK9 gene. Mutations engineered to mimic those associated with early onset PD in humans failed to provide protection. "These results suggest that one of the gene's functions is to protect cells from manganese," says Gitler. The relationship between PARK9 and alpha synuclein in yeast were later confirmed in additional Parkinson's models, including those in C. elegans and rat neurons, in collaboration with investigators at the University of Alabama and Purdue University. Lindquist says that the yeast model exploits the biological similarities between yeast cells and human cells, making it particularly well-suited to enhancing our knowledge of what actually happens in cells affected by Parkinson's. "Using yeast to study Parkinson's means that we will be able to start understanding the underlying pathobiology of the disease and eventually design rational therapeutic strategies based on what's causing the disease rather than what's the outcome," says Lindquist. "In other words, treating the root cause rather than the symptoms." http://www.wi.mit.edu/index.html