Summer 2004

Family Inheritance

IUSM researchers are leading an international project that studies the DNA of sibling to determine what role genetics plays in causing Parkinson’s disease.

For Judy Curtis, Parkinson’s disease is a family tradition. Not that the Indianapolis grandmother wants it that way; it’s just how the genes are stacked in her family. Her father had Parkinson’s. So do two of her brothers. One of her sons is being evaluated for the disease.

In all, she has five children and 14 grandchildren and that’s why she is in favor of genetic research for the debilitating movement disorder. She, along with her four siblings and all of her children are enrolled in a Parkinson’s disease genetic study at the IU School of Medicine and internationally.

“If you are predestined to have Parkinson’s disease, there is nothing you currently can do once you are diagnosed,” says Curtis. “My participation in the study probably won’t help my children – but it may help their children.”

A similar sentiment has been expressed by many of the people enrolling in the Parkinson’s Research: An Organized Genetic Initiative (PROGENI) study. The international research, funded by an $8.26 million National Institutes of Health grant seeks genetic causes for Parkinson’s disease by studying the DNA of siblings with the neurodegenerative illness.

On the Right Track

IU School of Medicine’s Tatiana Foroud, PhD, associate professor of medical and molecular genetics, is the principal investigator for the current five-year grant. This is the second round of funding, which, Foroud says, speaks volumes about the accomplishments of the first five years of research.

“When we initially applied for funding, we had to convince the NIH there was a possibility that Parkinson’s disease had a genetic basis,” says Dr. Foroud. “The original grant was funded in 1998 and we received $6 million. This time, our funding was increase by a third due to the success of the first five years of findings.”

That is good news for the 600 sibling pairs already taking part in PROGENI. Those brothers and sisters are from the United States, Canada and Puerto Rico, representing the 58 Parkinson’s Study Group centers affiliated with the study.

One of the discoveries of the first PROGENI study produced evidence of an expanded role of a gene on chromosome six known as the parkin gene. It was previously thought that the parkin gene only was involved in the development of juvenile or early onset Parkinson’s disease and then only when both copies of the gene were abnormal. But, it has now been determined that the gene may indicate a risk factor for developing Parkinson’s disease in older adults when only one of the two members of the gene pair is abnormal.

Dr. Foroud says one of the goals of the current study is to confirm the role of the parkin gene in the development of Parkinson’s. Another goal is to determine the role of a gene on chromosome 2 that appears to play an important role in the development of the disease in families with multiple affected members.

While Parkinson’s disease occurs in about two percent of individuals over the age of 75, only about ten percent of individuals with Parkinson’s also have a brother or sister diagnosed with the disease. This suggests that multiple genes influence whether an individual will develop Parkinson’s disease, notes Dr. Foroud.

X Marks the Spot?

Parkinson’s disease is more common in men and researchers remain unclear why that occurs. However, a finding from the PROGENI study soon may offer an explanation.

“We have some tantalizing hints that there may be a gene on the X chromosome that increases the risk of Parkinson’s disease among brothers with the disease,” says Dr. Foroud. “This gene does not appear to be significant in families where only sisters have Parkinson’s so we are hoping the gene may help explain why more men develop the disease.”

Perhaps one of the more exciting discoveries for geneticists and neurologist alike is the isolation of an area on chromosome 10 previously linked to late-onset Alzheimer’s disease. The PROGENI researchers believe it also may play a role in Parkinson’s disease.

“Physicians have known for years that there were similarities in the symptoms of Parkinson’s and Alzheimer’s diseases,” said Dr. Foroud. “Research now indicates there is a corresponding genetic link for at least some forms of the diseases.”

This research was initially presented in April at the American Academy of Neurology annual conference.

Alzheimer’s and Parkinson’s diseases are the two leading neurodegenerative illnesses of the elderly and both are characterized by the death of brain cells and the accumulation of proteins in various areas of the brain.

Sadly, some patients develop both disorders; estimates indicate that perhaps as many as 20 percent of Parkinson’s patients develop dementia and a similar percentage of Alzheimer’s patients may develop symptoms of Parkinson’s disease or have brain changes consistent with the disorder.

The PROGENI research has found that siblings with Parkinson’s disease are more apt to exhibit an area on chromosome 10 not typically found on the genome. A similar area on the same chromosome also is more common in siblings with Alzheimer’s disease.

“This gene is one of a number of genes that may have an impact on the onset of Parkinson’s disease on patients who develop the disease at different ages and in families with multiple affect members,” says Dr. Foroud. “This revelation was the result of the first five years of PROGENI.”

Brothers, Sisters Sought

The PROGENI study wants to enroll an additional 300 sibling pairs with Parkinson’s disease, bringing the total number of brothers and sisters involved in the study to 900 pairs. Participants in the trial have a comprehensive clinical examination to determine if they indeed have Parkinson’s disease according to guidelines established for this study. Participants also answer health questions and donate a blood sample from which DNA is extracted.

In addition to the nationwide study, the IUSM is conducting a related study called PROGENI CARES for residents of Indiana. This study allows same-sex friends and same-sex in-laws of individuals with Parkinson’s disease to participate in research and help geneticists identify and understand the genes that contribute to the disease. Dr. Foroud and her fellow researchers are seeking 500 individuals with Parkinson’s disease and 500 unrelated individuals without the disease.

Once again, blood samples are taken to extract DNA.

“The discoveries may have an enormous impact on early detection, treatment and on the development of new and more effective drugs for treatment of Parkinson’s disease,” Dr. Foroud says.

‘A Left-Side Transplant’

For Judy Curtis optimism is a way of life, but the 62-year-old grandmother isn’t certain new therapies will be available as soon as she might need this. Diagnosed about five years ago, Curtis says Parkinson’s disease really doesn’t slow her down although her husband Dave says he’s aware she drops things more than she used to.

So far the disease has only affected her left side. Her left hand is not as sure as it used to be. She also has a facial spasm in her left check. “I need a left-side transplant,” she jokes.

“The disease itself is not painful,” she adds. “If I had to chose, I’d have Parkinson’s disease over cancer.”

The Curtises do not dwell on her illness. They travel frequently and the décor of their family room reflects that as well as Judy’s primary craft interest: sewing. There are beautifully designed throw quilts, quilted pillows and wall hangings highlighting the room. She makes baby quilts for the James Whitcomb Riley Hospital for Children and St. Vincent’s hospitals. She also has sewn burial outfits for babies, as well as bibs, bunting and other clothing.

She has photos of granddaughters in delicate christening and confirmation dresses – garments that look as if they were designed by the lace makers of Brussels.

Sewing is a hobby and also a retreat from Parkinson’s disease for Judy. “I like being in my sewing room with my things,” she said. “I don’t have to worry about my shaking.”

She is passing her seamstress skills on to her granddaughters, who have an annual sewing project overseen by Grandma. That is one family tradition Curtis is happy to share with the next generation.