Morgan Foundation
The Musette and Allen Morgan, Jr. Foundation for the Study of Primary Sclerosing Cholangitis
Mission
Statement
The mission of the Musette and Allen Morgan, Jr. Foundation for the Study
of Primary Sclerosing Cholangitis is to sponsor and facilitate both basic
and clinical research to discover new treatments and ultimately a cure
for primary sclerosing cholangitis.
Musette and Allen Morgan, Jr. Foundation
for the Study of Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) is an inflammatory disease of the
liver involving the larger intrahepatic and extrahepatic bile ducts. The
disease is progressive and results in biliary obstruction and eventually
cirrhosis and liver failure. The disease is often associated with inflammatory
bowel disease, most often ulcerative colitis. The abnormal bile ducts
are often the site of bacterial infection. Another important clinical
feature of PSC is the propensity of patients to eventually develop cholangiocarcinoma,
which has a very high mortality rate and often precludes liver transplantation.
Currently, there is no cure for PSC, and drug therapy at best may only
slow the progression of the disease. Clinical and basic research is urgently
needed to find an effective medical treatment for this devastating disease
in both adults and children.
Musette and Allen Morgan, Jr. have made a substantial financial commitment
to begin a five-year strategic plan to develop a research center to focus
on primary sclerosing cholangitis (PSC). The mission of the Musette and
Allen Morgan, Jr. Foundation for the Study of Primary Sclerosing Cholangitis
is to sponsor and facilitate both basic and clinical research to discover
new treatments and ultimately a cure for PSC. Investigators supported
by the Foundation will be expected to use Foundation funding to develop
research projects that will ultimately be competitive for funding from
external sources, such as the National Institutes of Health, American
Liver Foundation and others.
Primary sclerosing cholangitis is an inflammatory disease of the liver
involving the larger intrahepatic and extrahepatic bile ducts. The disease
is progressive and results in biliary obstruction and eventually cirrhosis
and liver failure. The disease is often associated with inflammatory bowel
disease, most often ulcerative colitis. The abnormal bile ducts are often
the site of bacterial infection. Another important clinical feature of
PSC is the propensity of patients to eventually develop cholangiocarcinoma,
which has a very high mortality rate and often precludes liver transplantation.
Currently, there is no cure for PSC, and drug therapy at best may only
slow the progression of the disease. Clinical studies of therapeutic agents
have been hampered by the need for multicenter studies, since the disorder
is relatively uncommon, particularly in children and adolescents.
The pathophysiology of PSC involves dysregulation of the immune system
allowing targeted immune-mediated injury to bile duct epithelium. The
association of ulcerative colitis with PSC suggests that the inflammatory
process in the large intestine resulting in cytokine release, particularly
tumor necrosis factor-a, contributes to this process. Increased permeability
of colonic mucosa due to inflammation may result in the entry of bacterial
products and toxins into the portal circulation, which goes to the liver.
These substances may activate Kupffer cells and other immune cells in
the liver, resulting in targeted bile duct injury. The overlap of PSC
with autoimmune chronic hepatitis also supports an immune-mediated mechanism
of injury.
To date, limited clinical trials using immunosuppressive agents and ursodeoxycholic
acid have yielded generally disappointing results. Although ursodeoxycholic
acid is widely used and does result in improvement in biochemical parameters,
it has not been conclusively shown to improve ultimate clinical outcome.
Clearly, more research is needed to develop more effective therapeutic
approaches for this disease, in particular immunomodulatory therapy, other
than liver transplantation.
A Scientific Advisory Board has been organized and charged with the review
and oversight of all basic and clinical research projects, as well as
all research-related activities of the Foundation. This Board will make
research funding recommendations to the Administrative Board for approval.
The Scientific Advisory Board is currently comprised of Gene Whitington,
M.D., Director (Professor of Clinical Pediatrics, Pediatric Gastroenterology
and Hepatology), Dennis Black, M.D., Co-Director (Professor of Pediatrics
and Physiology, Pediatric Gastroenterology and Hepatology), Caroline Riely,
M.D. (Professor of Medicine and Pediatrics, Director, UT Adult Hepatology),
Russell Chesney, M.D. (Chair, UT Department of Pediatrics), Robert Wyatt,
M.D. (Professor of Pediatrics, Associate Director of the UT GCRC and Department
of Pediatrics Director of Clinical Research), Tony Marion, Ph.D. (Professor
of Molecular Sciences), and Radhakrishna Rao, Ph.D. (Associate Professor
of Physiology). External board members include Nicholas LaRusso, M.D.
(Professor of Medicine, Biochemistry and Molecular Biology, Division of
Hepatology and Transplantation, Chair of Internal Medicine, the Mayo Clinic
College of Medicine), Benjamin Shneider, M.D. (Associate Professor of
Pediatrics, Director of Pediatric Hepatology and Transplantation, Mt.
Sinai School of Medicine) and John Vierling, M.D. (Professor of Medicine
and Director of Hepatology, Cedars-Sinai Medical Center).
