According to a study by an international research team, carriers of a rare, genetic condition called Gaucher disease have a 5 times greater risk of developing Parkinson's disease.

Previous studies have linked several genes to Parkinson's disease and this study conclusively shows that mutations in the gene responsible for Gaucher disease are among the most significant risk factors found to date for Parkinson's disease.

Parkinson's disease, a neurological condition that typically causes tremors and stiffness in movement, affects about 1 to 2 percent of people over the age of 60. The chance of developing Parkinson's disease increases with age and involves a combination of environmental risk factors and genetic susceptibility.

Gaucher disease occurs when an individual inherits two defective copies of the GBA gene, which codes for an enzyme called glucocerebrosidase. This enzyme breaks down a fatty substance called glucocerebroside, which, when not properly disposed of, can harm the spleen, liver, lungs, bone marrow and, in some cases, the brain. The enzyme functions in a part of the cell called the lysosome, where cellular components are broken down, or metabolized, for recycling.

In the past, it was thought that people who carry just one altered GBA gene were unaffected. However, in recent years, research groups at the National Human Genome Research Institute (NHGRI) and elsewhere have completed small studies suggesting that carriers of GBA alterations may have an increased risk of developing Parkinson's disease.

The research team examined the frequency of GBA alterations in 5,691 patients with Parkinson's disease, including 780 Ashkenazi Jews, a population in which a particular type of Gaucher disease is more prevalent. Those data were matched against 4,898 unaffected volunteers, called controls, which included 387 Ashkenazi Jews.

At least one of the two common GBA alterations was found in 3.2 percent of Parkinson's patients and 0.6 percent of controls. Among the Ashkenazi subjects, 15.3 percent of those with Parkinson's disease carried a GBA alteration compared to 3.4 percent of Ashkenazi controls.

In addition to screening for the two common alterations, five of the research centers sequenced the entire GBA gene in 1,642 non-Ashkenazi patients with Parkinson's disease and 609 non-Ashkenazi controls. Using this more thorough method, they found many additional alterations associated with Parkinson's disease, and showed that 7 percent of patients carried an alteration, indicating that it is important to look beyond the two common alterations to gain a true picture of risk in the general population.

Besides significantly increasing the risk of Parkinson's disease, GBA alterations also appear to increase the likelihood of early disease onset. According to the new study, Parkinson's patients with GBA alterations developed symptoms an average of four years earlier than other Parkinson's patients.

Overall, the researchers found that the association between GBA and Parkinson's disease is not confined to any single ethnicity or to specific GBA mutations, though they did find that some gene alterations are seen more frequently in certain populations. Compared with the general population, in which GBA alterations occur in fewer than one out of 100 people, GBA alterations occur in at least one out of 16 people of Ashkenazi descent. However, many GBA mutation carriers as well as patients with Gaucher disease never develop Parkinson's disease, so this appears to be only one of several risk factors involved.

Parkinson's disease is a neurodegenerative disorder of unknown cause that affects nearly five million individuals worldwide.

Under a research grant from MJFF, Sigma Advanced Genetic Engineering (Sage) Labs - an initiative of Sigma-Aldrich's Research Biotech business unit - will use novel CompoZr zinc finger nuclease (ZFN) technology in an effort to create superior preclinical research models critically needed for the development of transformative treatments for Parkinson's disease.

The models, which are expected to take as little as one year to develop, will be made broadly accessible to scientists throughout the Parkinson's research community in order to speed basic research and drug development efforts field-wide.

Although current mammalian models adequately recapitulate some outward symptoms of Parkinson's disease, no existing model has been able to accurately mimic the onset and progression of the underlying disease processes that characterise the disease in humans.

Research already conducted into the genetic causes of Parkinson's disease has identified a number of genes but indicates a strong connection to mutations in five particular genes: LRRRK2, alpha-synuclein, DJ-1, Parkin and Pink1.

MJFF funding will allow Sigma-Aldrich's efforts to create five novel rat models with each of these genes knocked out.

Adopting a new approach to developing more effective and targeted research models, Sage Labs will use the CompoZr ZFN technology in its efforts to design 'knockout' rat models in which the genes known to be directly implicated in Parkinson's disease are omitted.

This research is expected to facilitate the development of new models that scientists believe will provide a better understanding of Parkinson's disease at the molecular, biochemical, physiological and behavioural levels.

This knowledge may, in turn, result in new therapeutic targets and approaches for the treatment of Parkinson's disease.

Because rats are physiologically similar to humans, they are ideal subjects for modelling human diseases and have been an important species for research in a number of fields including physiology, endocrinology, neurology, toxicology and cancer.

Until recently it has been impossible to create rat models with particular genes de-activated, or 'knocked out'.

However, using CompoZr ZFN technology, scientists at Sage Labs are able to generate animal models with targeted genetic changes to better understand gene function and develop new therapeutic approaches.

A group of doctors training at Beth Israel Deaconess Medical Center started a unique program last week to learn about genetic tests marketed to consumers, placing them in the vanguard of preparations to guide patients through the dawning Wild West age of personalized medicine.

Part of the instruction will come from having the young physicians test their own DNA in search of genes linked to various illnesses.

Private companies have begun offering a flurry of tests that purport to tell patients their genetic risks, for everything from Parkinson’s disease to obesity. Tests that can be ordered over the Internet need only a simple cheek swab to hunt for gene variations associated with particular diseases.

Ultimately, genetic tests offer the promise of dramatically improving and personalizing health care - guiding doctors to therapies tailored to a person’s genetic idiosyncrasies, or allowing patients to take preventive steps based on risks that lurk in their genes.

But today, the results can be hard to interpret and can mislead patients - and scientific understanding of the genetics of common diseases is still evolving - so the tests have drawn concern and opposition from much of the medical establishment. As the science races forward, in the lab and into the marketplace, doctors are realizing they need to be ready to assess the information and assist their patients.

“We can bury our head in the sand and pretend it’s not happening, we can suppress the information and tell patients not to go near it, or we can figure out strategies to play a constructive role as this new era of genomic and personalized medicine rolls out,’’ said Dr. Mark Boguski, an associate professor of pathology at Harvard Medical School who will be one of the instructors of the class. “That’s what we’re trying to do: prepare our trainees - not because the technology is ready for prime time today, but people are using it, and it’s clear it’s going to play a role in the future.’’

Doctors in their second and final years of pathology residency training will take the class - attending lectures and researching the science behind the tests. If they choose, they can look at their own test results, submitting a sample to the genetic testing company Navigenics.

Boguski said the inspiration for the class came from his own experience, when he used tests from three companies to learn more about his DNA and see what information the companies provided about various diseases and conditions. Examining his own data, he said, helped make the experience more immediate.

“I’m curious to see what’s there,’’ said Dr. Thomas Gage, a resident who said he would participate in the testing. “A lot of this stuff can be interpreted too easily sometimes. . . . So I think that’s where you have to be a little bit skeptical. Still, it’s information.’

The program is being offered to pathologists because they are the specialists who perform and interpret lab tests.

“This has always been our role: blood tests, cultures, urine, those samples come to pathology, where the test is done,’’ said Dr. Jeffrey Saffitz, chairman of the pathology department at Beth Israel Deaconess. “We see this personalized genomic analysis as a modern extension of our traditional role.’’

But the program is just a starting point in what will have to be an all-out effort to give medical professionals a good grounding in the use of genetics.

Dr. W. Gregory Feero, special adviser to the director of the National Human Genome Research Institute, said efforts are being made to increase genetic competency among medical professionals, including nurses, physician assistants, and specialists.

Many medical schools include genetics in their curriculum, he said, but the subject tends to drop out of the discussion as students progress from the “book years’’ to clinical practice.

The American College of Medical Genetics, a professional organization, has issued a cautionary statement about direct-to-consumer genetic testing. Much of the concern stems from consumers’ expectations, which have been set by the notion that a particular gene is responsible for a trait or a disease - determining eye color, for example, or whether a person has cystic fibrosis. But for common diseases, it appears that any single variant of a gene elevates risk only slightly - and the likelihood of falling ill is influenced by other factors, such as environment, lifestyle, and other genes that have yet to be identified. There is no evidence yet that finding out such information results in better outcomes, and great worry among physicians is that consumers who seek such information without medical advice may misinterpret their results.

Still, the organization’s president, Dr. Bruce Korf, said efforts like the one at Beth Israel Deaconess are essential to give doctors the ability to evaluate genetics information, even though most of it is not useful now.

“My personal view is we have relied way too much on lectures and not enough on innovative models based on case teaching or other simulations that are much more real than . . . hearing someone talk about something,’’ he said.

Dr. Joel Hirschhorn, an associate professor of genetics at Harvard Medical School who co-teaches a three-week genetics curriculum, said science is moving so fast that fourth-year medical students wouldn’t have been taught what this year’s first-year students will learn, so efforts like the one at Beth Israel Deaconess are important.