CHAPEL HILL – Medical scientists at the University of North Carolina at Chapel Hill have achieved wide renown for research on blood clotting disorders, cystic fibrosis, growth hormones, autism and laboratory mice genetically engineered to mimic a host of human illnesses.
Now, they also have taken the lead in research and treatment of primary ciliary dyskinesia, or PCD, a relatively rare inherited disease that's estimated to affect more than 15,000 Americans. Cilia are the microscopic hair-like structures that line the airways and beat in unison to sweep the lungs clear of dust and secretions trapping disease-causing organisms. Impairment of this natural cleansing mechanism boosts the risk of illness.
This year, on the 100th anniversary of the first report of the condition in a medical journal, UNC physicians and scientists are teaming with the fledgling PCD Foundation to present a national family education weekend. The event will take place at the Millennium Hotel in Durham, N.C., Friday through Sunday (July 16-18).
"We anticipate about 45 patients and their families and have a roster of speakers primarily from UNC," said Michele Manion, president of the foundation and mother of Meghan, a PCD patient diagnosed at age 7 and now in her third year of college. "The goal of the weekend is to update attendees on research progress and advances in treatment and to provide a forum for people affected by PCD to share information and support."
Meghan, who trains horses, is doing very well, her mother said.
"Her disease causes her some limitations, but she is determined to live a full and rewarding life and works her disease around her life instead of vice versa," Manion said.
The Primary Ciliary Dyskinesia Family Education Weekend is "a continuation of our interest and commitment to achieving a better understanding of respiratory health and disease," said Dr. Johnny Carson, professor of pediatrics and cell and developmental biology at the UNC School of Medicine. Carson also is one of the world's top experts on cilia function.
"Even though the syndrome has been recognized for a century, the beginnings of our understanding had to await the advent of electron microscopy about 30 years ago," Carson said. "That was when medical scientists recognized that cilia in affected people exhibited specific lesions visible only by the electron microscope."
Abnormalities in cilia lead to loss of function, chronic airway disease and infertility, said the researcher, whose laboratory is the nation's leading center for PCD diagnosis. Since genetic markers for the syndrome are just beginning to be discovered, electron microscopy remains the gold standard for diagnosis.
"Moreover, the application of electron microscopy is essential for new research aimed at identifying the genetic basis for the syndrome by characterizing the specific ultrastructural abnormalities among different patients and relating those to their genetic pedigrees," Carson said.
Dr. Michael R. Knowles, professor of medicine and co-director of the Adult Cystic Fibrosis Program at UNC, said he and colleagues have applied for and anticipate receiving a new $4.7 million National Institutes of Health grant from the National Center for Research Resources' Office of Rare Diseases in support of their PCD efforts and related work on cystic fibrosis and pseudohypoaldosteronism.
Dr. Margaret Leigh heads the clinical arm of the effort, and Dr. Maimoona Zariwala is leading the genetic component, he said.
"Dr. Leigh and I have put together a consortium of other institutions in Denver, Seattle and St. Louis that will collaborate with us on new research," principal investigator Knowles said.
"Also, Dr. Leigh is coordinating an additional clinical network of 12 sites across the country from which we also expect good things," he said. "She has pulled together a group of uniquely talented young investigators and is embarking on a prospective study of the early disease in infants with PCD, including measures of lung function in infants, which is a newly applied technology in pediatrics."
"The PCS Foundation has been instrumental in helping us to establish UNC as the top U.S. referral center for clinical care and research on this rare disease," Knowles said. "We are excited about the progress we will make in reducing the burden PCD patients and their families have to bear."
Zariwala, research assistant professor of pathology and laboratory medicine, is pioneering molecular diagnostics to boost understanding of the syndrome, he said.
"Her primary aim is to define the genes causing PCD," Knowles said. "Many genes participate in the construction of cilia, hence PCD is a genetically heterogeneous or complex disorder. That makes it challenging to define its genetics because mutations in more than one gene and different mutations in the same gene can cause the disease."
She and colleagues have developed a systematic approach to expedite the mutation detection process, he said.
"We have defined several disease-causing mutations in some of our PCD families," Zariwala said. "Using this information, we hope to develop clinical testing for PCD families, which will help improve diagnostic capabilities and help in counseling families."
Genetic testing is clearly the wave of the future for PCD, Knowles said, and widespread genetic testing will be available within a few years.
"When Meghan was diagnosed, we were told that the diagnosis was so rare and scientific interest so minimal in the disease that we should not expect any advances in research," Michele Manion said. "That was, of course, devastating news."
Manion was not one to give up, however, and before long she launched her own personal effort to improve the situation for her daughter and others. Among the results have been the foundation, which now has more than 300 patients and their families and has begun reaching out to thousands of others.
"I was ecstatic when I ran across the UNC PCD research website maintained by Drs. Knowles and Peadar Noone, among others," she said. "Knowing that there was a strong academic facility interested in pursuing PCD research gave us the boost we needed as a patient group to organize our efforts. The support and continued interest of UNC and the caliber of its pulmonary researchers cannot be overstated."
In describing her illness, Meghan said she often has trouble breathing.
"I suffer from chronic sinus pain and pressure and have a nasty-sounding cough most of the time," she said. "I sometimes get tired easily and have real difficulty with humidity. Over the years, I've gotten pretty good at ignoring all of this stuff, until I get pneumonia."
Meghan considers herself mostly normal, she said.
"I run three or four days a week, work full time, go to college full time, and, best of all, train horses full time," she said. "I'm fairly driven and energetic and seldom let anything stop me from reaching my goals. You can probably imagine the extreme frustration for me when I get sick and end up in the hospital where my life essentially stops for the week that I'm in there."
To counteract the effects of her disease, Meghan uses a device called "The Vest" twice a day to help her cough up lung secretions that could get infected and takes oral antibiotics.
"I also use inhalers and inhale antibiotics through a nebulizer," she said. "Running and riding are great for me, too."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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