Alpha-1 and CLiC

I thought I'd share the article I wrote for the Alpha-1 News

A Quest for Answers

A persistent question within the Alpha-1 community is why some individuals are liver-affected, lung-affected, or both. In the last few years, Dr. Ronald Sokol, Professor of Pediatrics at the University of Colorado School of Medicine and The Children’s Hospital in Denver, led a group of investigators to form the Cholestatic Liver Disease Consortium (CLiC) in an effort to begin to understand why some Alphas develop liver disease in childhood. As the principal investigator of CLiC, Dr. Sokol’s mission is to find answers to questions.

“One of the most important questions” says Dr. Sokol “is why do some people, particularly children, develop liver problems and others don’t, yet they have the same genetic mutation in the Alpha-1 gene. Only 10-15% are recognized as having a liver problem during childhood, and it is usually during the first few months or first few years of life. Sometimes the liver problem is quite severe, requiring liver transplantation in childhood.”

CLiC is a collaborative team of doctors, scientists, nurses, research coordinators, statisticians and patient support organizations throughout the US and UK, working together to improve the lives of children affected by rare cholestatic (poor bile flow) liver diseases. Alpha-1 Antitrypsin Deficiency is one of these diseases. The purpose of CLiC is to provide a way for patients and families to partner with doctors and researchers by participating in research studies.

With the infrastructure in place to make CLiC run, a research study is now under review and hopefully approved very soon. Dr. Sokol shared, “We’re going to conduct a longitudinal study of Alpha-1, in which we will follow for 5 years up to 250 children and young adults up to the age of 25 years with Alpha-1 and liver problems. One of the major purposes of the study is to define the natural history of Alpha-1 liver disease.”

There are many questions to be answered, and Dr. Sokol explains the theory, “There must be some other factor involved, either in the Alpha-1 gene, in other genes, or an environmental factor. We hope to be able to start to address this by collecting DNA from the children and their parents to eventually look for other genes that might be inherited along with the Alpha-1 gene that would increase the susceptibility to liver disease or protect against liver disease.”

In order for this important research to go forward, there must be enough research participants to make the study effective. “We will make no progress in understanding Alpha-1 Antitrypsin Deficiency to any great extent, its effects on children, and the course of their liver disease without the participation of families. The individuals, who actually have the most to gain, are the affected families and the children. Without their participation we’d really never be able to understand this disease better or develop new therapies to give them a better outlook.”

Dr. Sokol adds, “We are trying to build the largest series of children with Alpha-1 to ever be in a single database. We will collect and store DNA and other information all linked to each other, in an ethically appropriate and confidential manner, for conducting clinical research in 2007 and beyond.”

Signing up to participate in the research conducted by CLiC is quite simple. CLiC operates a confidential contact registry, which
is available on its Web page: http://rarediseasesnetwork.org/clic. Dr. Sokol says, “For people around the country, that is the simplest way to become registered as being interested in this study. When the study is running, you will be given more information, and you can then make a choice about participation.”

When the study is approved and enrolling patients, research participants would be seen at one of the eleven CLiC clinical research centers participating in the study. “We would see the children as an outpatient once a year for five years. If the child has already undergone a liver transplant, we’d only see them one time for this study,” says Dr. Sokol. The list of participating centers appears on the CLiC Web site.

Only those individuals under the age of 25, who have SZ or ZZ phenotypes will be studied. Dr. Sokol explains, “In the study we will be collecting serum, urine, and blood (for DNA). This will help us to establish a biobank or a tissue repository that is linked to clinical information, so that investigators can ask/answer specific questions about Alpha-1 liver disease; this approach has not been taken in the past for children with Alpha-1 liver disease.”

CLiC is one of the Rare Disease Clinical Research Consortia funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the Office of Rare Diseases, and the National Center for Research Resources of the National Institutes of Health (NIH). The project scientist is Patricia Robuck, Ph.D Additional funding comes from the Alpha-1 Foundation.