Down syndrome is the target of ambitious NIH research initiatives

Washington -- Down syndrome is a familiar condition, affecting about one in every 800 children born in the United States. Although it is the most frequent genetic cause of mild to moderate mental retardation and it is associated with numerous other medical problems, much about it remains unknown.

The National Institutes of Health proposes to change that with an ambitious research agenda intended to advance understanding and speed treatments.

The agenda, released Jan. 22, sets out objectives for the next 10 years that cover disease progression, diagnosis and screening as well as treatment and management. It also includes medical, cognitive and behavioral conditions that occur more frequently in people with Down syndrome, such as leukemia, heart disease, sleep apnea, seizure, stomach disorders and mental health problems.

Most frequently, the syndrome results from an extra copy of chromosome 21 in all of an individual's cells. In a small number of cases, the extra chromosome 21 is present in some cells. Also in a few cases, individuals have the normal number of chromosomes but carry portions of material from chromosome 21 on other chromosomes.

The effects of this aberration are registered in many parts of the body. In addition to affecting physical appearance, the syndrome can cause hearing loss, heart malformations, hypertension, digestive problems and vision disorders.

The agenda was established by representatives from several NIH institutes and led by the National Institute of Child Health and Human Development. The group also identified the need to study whether aging has a greater impact on mental processes in people with the syndrome. Congress had asked last year that the NIH explore this issue.

Roger Reeves, PhD, a Down syndrome researcher and professor of physiology at Johns Hopkins University School of Medicine in Baltimore, applauded the NIH initiative. "It's a really important step in dealing with a syndrome that affects so many different aspects of people who have an extra copy of chromosome 21."

A challenge, as Dr. Reeves sees it, will be for all the institutes to find ways to interact with one another. "Each institute lists different kinds of projects in Down syndrome, each focused, unsurprisingly, on their own missions." Targeted areas range from improving animal models to studying real-world outcomes for Down syndrome families.

The involvement of NIH Director Elias Zerhouni, MD, could provide needed leadership, Dr. Reeves said.

"Through the years, the NIH research effort has led to increased understanding of Down syndrome. We are now poised to capitalize on these advances and improve the health of people with Down syndrome," Dr. Zerhouni said during his announcement of the agenda.

A variety of agendas

The agenda was assembled at the urging of advocates for people with the syndrome who caught the attention of Congress, said Brian Skotko, MD, a pediatrician at Children's Hospital in Boston and a long-time advocate for people with the syndrome, including his sister.

"Down syndrome is the most common chromosomal condition that mankind has, yet surprisingly, the NIH, the [Centers for Disease Control and Prevention] and the national Down syndrome movement have never had a focused research agenda," he said. This circumstance has occurred despite the fact that other disability and medical conditions that occur in far fewer people have such agendas, he added.

Now it appears that the syndrome will have three separate research agendas as the NIH effort is expected to be joined shortly by a CDC agenda and one developed by the Down Syndrome Research Coalition, an assembly of advocacy groups and physicians, Dr. Skotko said. He worked on developing the CDC agenda.

The challenge, similar to that described with the NIH agenda, will be to reconcile the different approaches recommended by the three organizations, he said.

The NIH agenda focuses on the scientific and the molecular underpinnings of the syndrome while the CDC will focus on the public health ramifications, the epidemiology and the statistics, he said. The agenda being developed by the National Down Syndrome Society and the National Down Syndrome Congress will include all of the above plus whatever the advocacy groups identify as the research gaps, said Dr. Skotko, who serves on the NDSS board.

Dale Ulrich, PhD, professor of kinesiology and director of the Center for Motor Behavior and Pediatric Disability at the University of Michigan in Ann Arbor, called the NIH agenda a "critical first step." He also would like to see a focus on recruiting more researchers to work in this area.

Funding an issue

But the funds needed to carry out these agendas are missing, all concurred. NIH funding for Down syndrome research has decreased from $23 million in fiscal 2003 to $17 million in 2008, Dr. Skotko noted. In comparison, autism research, which should remain intact, he stressed, is funded at $128 million for this year.

In addition to the lack of funds, the lack of a national registry of people with Down syndrome also is obstructing progress, Dr. Skotko said. "No one is stepping up to the plate. The NIH doesn't identify the national registry as a priority, the CDC will mention it in a preamble when its agenda is released and the national Down syndrome groups don't have the funds for it."