Related Experiment Videos

New targets in and potential treatments for cholesterol gallstone disease

Sheila A Doggrell1

  • 1Auckland University of Technology, Division of Health Practice, Akoranga Campus, Northcote, Auckland, New Zealand. s.doggrell@xtra.co.nz

Current Opinion in Investigational Drugs (London, England : 2000)
|April 22, 2006
PubMed

Insights

Gallstone disease affects millions annually. Targeting the bile acid receptor (FXR) with agonists like GW-4064 or specific bile acids shows promise in preventing cholesterol crystal formation and treating gallstone disease.

Area of Science:

  • Hepatology
  • Gastroenterology
  • Molecular Endocrinology

Background:

  • Gallstone disease is prevalent, particularly in certain ethnic groups, affecting millions of Americans.
  • The nuclear farnesoid X receptor (FXR) plays a role in bile acid metabolism and gallstone formation.
  • Genetic susceptibility, like in C57L mice, highlights the need for therapeutic targets.

Purpose of the Study:

  • To investigate the role of FXR in gallstone susceptibility.
  • To evaluate the efficacy of FXR agonists in preventing cholesterol precipitation.
  • To explore novel therapeutic strategies for gallstone disease.

Main Methods:

  • Utilizing FXR knockout mice and C57L mouse models fed a lithogenic diet.
  • Administering small-molecule FXR agonists (e.g., GW-4064).
  • Investigating the effects of bile acids and their derivatives on cholesterol crystallization.

Main Results:

  • FXR knockout mice exhibit increased susceptibility to gallstone formation.
  • GW-4064 treatment prevents cholesterol precipitation in susceptible mouse models.
  • Certain bile acids and fatty acid conjugates demonstrate potential in managing cholesterol crystallization.

Conclusions:

  • FXR activation is a viable therapeutic strategy for gallstone disease.
  • Small-molecule FXR agonists and specific bile acid derivatives show promise for prevention and treatment.
  • Modulating hepatocyte bile acid transporters may offer additional treatment avenues.

Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Cholecystitis01:20

Cholecystitis

Cholecystitis is inflammation of the gallbladder, most commonly caused by obstruction of the cystic duct. This blockage prevents bile from draining, leading to gallbladder distension, inflammation, and potentially serious complications. This condition may present acutely or chronically and can happen with or without gallstones.EtiologyAbout 95% of cholecystitis cases are calculous, caused by gallstones blocking the cystic duct, leading to bile accumulation and inflammation of the gallbladder...
Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Chronic Pancreatitis II: Collaborative Care01:29

Chronic Pancreatitis II: Collaborative Care

The management of chronic pancreatitis is multifaceted, involving a comprehensive approach that includes thorough assessment, diagnostic testing, and a variety of management strategies.
Assessment:
Acute Pancreatitis II: Clinical Manifestations and Management01:30

Acute Pancreatitis II: Clinical Manifestations and Management

Acute pancreatitis presents a complex medical emergency characterized by rapid onset inflammation of the pancreas, demanding timely diagnosis and management to prevent complications. The condition primarily manifests through severe upper abdominal pain that often radiates to the back. This pain intensifies following the consumption of fatty foods. Accompanying symptoms such as nausea, vomiting, abdominal distention, fever, dyspnea, cyanosis, and jaundice can vary in intensity but significantly...