http://newsobserver.com/tuesday/news/Story/816899p-811279c.html

 

Published: Tuesday, September 4, 2001 4:11 a.m. EDT

New hope in Down syndrome
Alzheimer's drug may improve abilities

		Mollie Tew, 11, looks through a book on Down syndrome that includes a quote by her, while clinical psychologist Gail Spiridigliozzi, right, interviews Mollie's mother, Vickie Youngblood. Mollie is participating in a study at Duke. Staff Photo By Scott Lewis
		STORY TOOLS
		printer friendly version send this story to a friend
		SITE TOOLS
		subscribe to our e-mail lists get news, weather, movies on your PDA

By MEGAN MILLER, Staff Writer

Sally Austin remembers well the day her newborn daughter Sarah was diagnosed with Down syndrome. Looking out over the University of North Carolina at Chapel Hill campus from her hospital window, she thought about how her child would probably never go to college. "I grieved about that," she said. Now, 14 years later, there is a glimmer of hope that a treatment led by a Duke doctor will help people like Sarah better achieve an education and live fuller, more independent lives.

Down syndrome affects about 1 in 1,000 children born in the United States. Various health problems result from a child's having an extra copy of chromosome 21. Heart defects, intestinal tract abnormalities and eye, ear and thyroid problems are common. Mental retardation -- delayed language development and learning in general -- affects almost all children with Down syndrome, and there is no available treatment.

New hope arose in 1999 when a study performed by Duke University pediatrician Priya Kishnani showed improved communication, language skills and other cognitive abilities in four patients taking a drug previously used to treat patients with Alzheimer's disease.

Last week, Duke University Medical Center launched its arm of a nationwide, multicenter trial to determine whether the drug commercially known as Aricept is the first treatment to help people with Down syndrome overcome cognitive deficits.

"Expressive language and communication skills are very difficult for them," said Kishnani, who sees patients with Down syndrome at the

clinic she helped establish at Duke six years ago with Dr. Gordon Worley. Math is another area that typically proves challenging for kids with Down syndrome, Kishnani said.

Thanks to improved medical care, people with Down syndrome are living longer -- up to age 55 on average as compared with age 9 a century ago, according to the National Down Syndrome Society. As a result, a growing number of adults with Down syndrome require help living independently.

Without any available treatment for the mental deficiencies associated with Down syndrome, many parents have turned to alternative therapies -- vitamins, minerals, even an experimental and unproven drug called Piracetam -- to improve their children's abilities.

Kishnani met one day with two colleagues in psychiatry, Dr. Ranga Krishnan and Dr. Murali Doraiswamy. She listened as they described the impressive gains in memory and cognitive ability that Alzheimer's patients were showing when given a drug called donezepil hydrochloride, or Aricept. Knowing that Down syndrome patients often show the same changes in brain chemistry as Alzheimer's patients, Kishnani wondered whether the drug could do the same thing for them.

"This is the first FDA-approved medication for which I thought there is a rationale for using it for Down syndrome patients," she said.

Aricept raises levels of a key chemical called acetylcholine used in the brain and nervous system to send messages between cells.

In 1997, Kishnani began a small pilot study of four adult patients with Down syndrome given Aricept for nine months and found exciting results: improved communication, use of expressive language, attention and mood stability.

The success of the small but promising study brought funding from the drug's creator, Pfizer, for the large multicenter trial beginning now at sites around the country, including Duke.

"Her early pilot data was encouraging, and I think that it made us all want to get involved," said Bonnie Patterson, a pediatrician at Children's Hospital Medical Center in Cincinnati who has run a Down syndrome clinic there for 16 years.

"I think it's a start in using some kind of medication intervention to improve cognition [in people with Down syndrome]," Patterson said. She emphasized the importance of the multicenter trial to test the long-term safety of the drug.

The multicenter trial will enroll approximately 160 people, ages 18 to 35, at about 20 centers. Half of the participants will be given Aricept and the other half will get a placebo over a 12-week period. The results may be known as early as 2002, said Susan Yaren, a spokeswoman for Pfizer.

Between the initial study and the multicenter trial, Kishnani has been conducting other small-scale trials of Aricept in Down syndrome patients, which will help determine whether the drug is safe and effective.

Twelve-year-old Mollie Rose Tew is a participant in one of these small-scale studies.

Though it is too early to tell whether the Aricept she has been taking for 16 weeks is helping, Vickie Youngblood has noticed an improvement in her daughter's reading comprehension, multiplication table memorization and overall pace of learning.

Kishnani would love to see similar improvements in all the kids she sees at the Duke Down syndrome clinic who come from all over the Southeast the first Thursday of each month. She performs checkups, catching problems that are common in children with their condition but could go unnoticed by general health care providers. She also helps put each child's developmental progress in perspective for parents.

"The encouragement is great," said Brenda Fuller, mother of 5- year-old Justin, who has been seeing Kishnani since he was 6 weeks old. "She always sees progress.

Fuller and her husband, Harvey, who come to the clinic from Virginia, said they would be interested in using a drug such as Aricept to improve Justin's ability to learn if it was proved effective and safe.

Kishnani and Brian Skotko, a recent Duke graduate who worked with the doctor throughout his undergraduate career and whose sister Kristen has Down syndrome, co-wrote a book called "Common Threads: Celebrating Life with Down Syndrome," released this summer by Band of Angels Press. Kishnani's patient Mollie Tew is among those featured in the book.

"People like Priya have affirmed and reinvigorated my passion for medicine," said Skotko, who starts Harvard Medical School this fall and plans to go into pediatric medicine and work with people with disabilities.

Kishnani herself was inspired by the work of other doctors -- her mother and grandfather practiced medicine in India, where Kishnani received her degree before coming to Duke for her residencies in pediatrics and genetics. Though her choice of pediatric genetics as a field was at the urging of her husband, she soon found her niche there, caring for children with Down syndrome.

"I enjoy the children very much," Kishnani said. "I just love their personality -- they're so selfless. They give you so much joy."

That first Thursday each month, clinic day, holds a special place in her planner and her heart.

"That's the best day of the month," she said.

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.