The National Institutes of Health has selected Oregon Health & Science University Doernbecher Children's Hospital to lead one of 19 clinical research groups dedicated to finding new approaches to the diagnosis and treatment of rare diseases. The new and returning research teams represent the second phase of the NIH's Rare Diseases Clinical Research Network (RDCRN) initiative and together will receive $117 million during the next five years to investigate more than 95 rare diseases.

"We are thrilled the NIH chose to fund the Sterol and Isoprenoid disease Research, or STAIR, consortium that we initiated,"said Robert Steiner, M.D., F.A.A.P., F.A.C.M.G., principal investigator for STAIR, Credit Unions for Kids Professor of Pediatric Research, Professor of Molecular and Medical Genetics, and Vice Chairman for Research in Pediatrics, OHSU Doernbecher Children's Hospital.  

OHSU Doernbecher will lead a multicenter international team of investigators focused on a group of rare diseases with a common biochemistry and health impact: sterol and isoprenoid diseases. The STAIR consortium will conduct two major clinical trials and six pilot research studies during the next five years.

The first clinical trial will focus on Smith-Lemli-Opitz syndrome, a genetic disorder in which the body doesn't produce enough cholesterol, an essential component of cell membranes and myelin, a fatty material that protects nerve fibers. Children with with syndrome can have various birth defects and mental retardation. Symptoms can include feeding problems, weak sucking and swallowing and limited ability to gain weight. There currently is no cure.

Katie Lucas, 5, of Portland, has participated in Smith-Lemli-Opitz syndrome clinical research since she was first diagnosed at OHSU Doernbecher at age 9 months. Immediately following diagnosis, Katie's parents enrolled her in a clinical trial, led by Steiner, in which children who have the syndrome are given a medication called a statin to prevent the buildup of abnormal chemicals. Katie's mom, Kathy Lucas, says Katie has "made huge leaps" participating in the trial.

"Her behavior is better, she's slept better and she's made progress in her neurocognitive and behavioral assessments. We are lucky that we had access to this research," Kathy said. "Knowing there are more dollars to support it gives us hope. It helps us to know someone is passionate about this and that they are continually working on it. I believe there are so many children who are undiagnosed and the attention this research could bring to these diseases may help find those lost children and give their parents an answer and some hope."

Children enrolled in the study will visit one of the STAIR clinical sites once a year and have state-of-the-art blood and urine testing, extensive neurocognitive testing (thinking, reasoning, concentration, memory, learning, etc.) and behavioral assessments, as well as sophisticated brain imaging. Data from this study will be entered in a central database, managed by the network's Data Management and Coordinating Center at the University of South Florida, and will be used to learn more about disease causes and response to current treatments, as well as to develop more effective therapies. Enrollment is projected to begin in spring 2010.

According to the NIH, a rare disease is defined as a disease or condition that affects fewer than 200,000 people in the United States. To date, approximately 6,500 such disorders have been identified, affecting an estimated 25 million Americans.

"Now clinicians and scientists at six centers are collaborating to design the best research possible in an attempt to develop treatments for these conditions," said Jean-Baptiste Roullet, Ph.D., STAIR Project Director and Research Associate Professor in the Department of Pediatrics, OHSU Doernbecher. "Some of the disorders we are studying have never had clinical trials because of their rarity, and that will now change as a result of this funding."

STAIR also will collaborate with patient advocacy and support groups, including the Smith Lemli Opitz/RSH Foundation, Ara Parseghian Medical Research Foundation, Foundation for Ichthyosis and Related Skin Types, the United Leukodystrophy Foundation and others. Advocacy and support groups play a critical role in the research network's operations, activities and strategy, meeting frequently with investigators throughout the year via teleconference and face-to-face meetings, and participating in network-level discussions and meetings.

In addition, STAIR will support a full-scale training program for investigators who are interested in the field of sterol and isoprenoid diseases — Andrea DeBarber, Ph.D, Research Assistant Professor in the Department of Physiology and Pharmacology at OHSU has been chosen as the first trainee. The consortium also will contribute new content for an NIH online educational and resource site.

Diseases STAIR will specifically explore include: Niemann-Pick disease type C, Smith-Lemli-Opitz syndrome, Sjögren-Larsson syndrome, Mevalonate kinase deficiency, Hyper-IgD syndrome, Cerebrotendinous xanthomatosis (CTX), and Sitosterolemia, a condition discovered by the late William Connor, M.D., a revered OHSU clinicianand scientist and Dr. Steiner's research mentor who died in November 2009.

Institutions participating in OHSU-led STAIR include: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Cincinnati Children's Hospital Medical Center, University of Nebraska Medical Center, and University of Manitoba (Canada).

According to the NIH, the Rare Diseases Clinical Research Network consortia were selected based on their "clinical research strengths and resources, a long history of collaboration, a diverse geographic distribution to allow optimal access by potential research subjects, their individual motivation to improve the health of patients, and the commitment of their institution to support the consortium."

Prior to the creation of the RDCRN, the NIH funded individual rare diseases in their respective disease type or organ. Patient recruitment was a challenge because so few affected patients lived in any one area. Since its launch in 2003, the Rare Diseases Clinical Research Network has enrolled more than 5,000 patients in 37 clinical studies in rare diseases. It is the first program to create a specialized infrastructure to support rare diseases research nationwide.