K. Michael Gibson PhD and Phillip L. Pearl MD SSADH study to define biomarkers for gauging intervention in future, more comprehensive clinical trials. For more information or if you are interested in participating in the study please email them at [email protected] or [email protected]
National Institute of Health Grant Application
MSA Committee submits NIH RFA RR-03-008
Principal Investigator- K. Michael Gibson PhD


In November 2002, the Rare Disease Act of 2002 directed the Office of Rare Diseases (ORD), National Institute of Health (NIH) to support regional centers of excellence for clinical research into, training in, and demonstration of diagnostic, prevention, control, and treatment methods for rare diseases. This law provides the legislated mandate for RFA RR-03-008 to address the needs of rare disease clinical research.

On February 27 2003, several combined institutes of the NIH including ORD released a Request For Application (RFA) for a 7 .0 million dollar grant that will fund 4 Rare Disease Clinical Research Centers (RDCRC) dedicated to research on 4 different rare disease groups and 1 Data and Technology Coordinating Center (DTCC). For detailed information on this grant and project please visit or

The concept of the RDCRC's is to develop a systematic approach for research in rare diseases. Giovanna Spinella MD, Director of Extramural Research at the Office of Rare Diseases explained during a recent teleconference; "A longitudinal study of the diseases must be included in the proposal because one of the main goals is to include a systematic approach so that if therapy X becomes available today there is a sense of what measures and outcomes should be reviewed. Rather than wait for a potential therapy to come down the road the concept is that we will already have this information. "

This is a groundbreaking opportunity for rare diseases and our children. The PND Association has been working with members of our MSA and is assisting with the completion of this proposal. Clinical protocols are being designed to consider the specific needs of our children and families. Depending on the particular disease children and families will visit the respective institution and participate in the studies.


The RDCRC working on behalf of PND's will consist of a consortium of clinical investigators, institutions and relevant organizations focused on the following diseases; SSADH, TH Deficiency, AADC, GTPH Deficiency and other BH4 defects without hyperphenylalanemia.

The proposal for the RDCRC will include;
Longitudinal and clinical studies.
A plan for the training of new clinical investigators for PND's
Resources to be included in a website for education and research.
Databank containing secured, private information to be utilized for future
studies and available treatment of the diseases.

The key personnel and participating institutions are identified below.

K. Michael Gibson, PhD, FACMG
Principal Investigator
Professor of Molecular and Medical Genetics and Pediatrics
Director, Biochemical Genetics Laboratory
Oregon Health Sciences University
Portland, Oregon 97201

Keith Hyland PhD
Director of Neurochemistry Laboratory
Baylor University Medical Center
3812 Elm Street
Dallas, TX 75226

Kathryn J. Swoboda, MD
Pediatric Neurology and Genetics
Primary Children's Medical Center
100 North Medical Drive
Salt Lake City, UT 84132

Darryl C. DeVivo, MD
Professor of Pediatrics and Neurology
Columbia University School of Medicine
New York, New York

Edward J. Novotny, Jr. MD
Associate Professor of Pediatrics and Neurology
Director, Pediatric Epilepsy Program
Yale University
3333 Cedar Street
New Haven, Conn 06510

Phillip L. Pearl, MD
Associate Professor of Pediatrics and Neurology
Children's National Medical Center
George Washington University School of Medicine
111 Michigan Avenue, NW
Washington, DC 20010-2970

Investigators outside the USA are:

Georg F. Hoffmann MD
University of Heidelberg
Im Neuenheimer Feld 153
Heidelberg, Germany 69120

Masay Segawa MD, PhD
Segawa Neurological Clinic for Children's Hospital
203 Surugadai Kanda Chiyoda-ku
Chiyoda-Ku, Tokyo 101
Tokyo 101-0062 Japan

Cornelis Jakobs, PhD
Departments of Pediatrics and Clinical Chemistry
VU University Medical Center
Amsterdam, The Netherlands

Knockout Mouse Model

The use of transgenic mice has begun to revolutionize the study of human inborn errors of metabolism. Disruption of specific genes in mice enables a researcher to study the "human" counterpart disease in a model system (mouse) which produces rapidly. This approach has recently been applied to SSADH deficiency. In November of 1999, the first mice with genetically altered SSADH were born. These animals have a short life span, and manifest behavioral and gait abnormalities as seen in the human disease. In addition, seizures are a common finding, and may ultimately be the cause of death. These new knockout mice are the subject of intense investigation, and new therapeutic approaches are being attempted in them. The development of useful therapeutics will ultimately have important benefits to those with the human disease. This work is under the supervision of Dr. K. Michael Gibson, Associate Professor, Department of Molecular and Medical Genetics, Oregon Health Sciences University.

Recently, Dr. Gibson was awarded a research grant through NIH to help support this important work.

To help fund this important research, please mail your contributions to:

GHB Research Fund
c/o Finance Manager
Oregon Health Sciences University
Department of Molecular and Medical Genetics
Mail Code L-103
3181 S.W. Sam Jackson Park Road
Portland, Oregon 97201-3098


2003 Pediatric Neurotransmitter Disease Association