Primary Sclerosing Cholangitis (PSC) Drug Development

The rarity and progressive nature of primary sclerosing cholangitis (PSC) underscore both the difficulty in conducting long-term or large-scale studies in addition to the importance of continued investigative work on viable treatment options for patients with this disease. Equipped with advanced facilities, professional experts, and experienced technicians, Creative Biolabs is confident in providing customer-satisfied cell-based therapy and antibody development services for global researchers.

Introduction to PSC

PSC is a rare cholestatic liver disease that is characterized by intrahepatic and/or extrahepatic structuring of the biliary duct system. Most common in Northern Europe and North America, its reported incidence in these countries is approximately 0.3 to 0.5 cases per 100,000 person-years. Approximately 70% of patients with PSC have inflammatory bowel disease (IBD) with a predominance of ulcerative colitis (UC). One of the most prominent prognostic models for this disease is the Mayo Risk Score which takes into account age, bilirubin, aspartate aminotransferase level, albumin, and history of variceal bleeding to predict survival in this patient population. These patients are also at risk for both hepatobiliary cancer and colorectal cancer. The presentation of PSC can include signs of cholestasis with jaundice, pruritus, fatigue, or right upper quadrant pain along with elevated alkaline phosphatase (ALP).

The principle aspects of bile duct lesions in PSC. Fig.1 The principle aspects of bile duct lesions in PSC. (Jiang, 2017)

Current Pharmacologic Management

  • Ursodeoxycholic acid
  • Ursodeoxycholic acid (UDCA) is currently not accepted as a standard of care, but it has been extensively investigated in the treatment of PSC. Its protective effect is thought to be secondary to the protection of cholangiocytes against the cytotoxicity of hydrophobic bile acids, stimulation of hepatobiliary secretion, and protection of hepatocytes against bile acid-induced apoptosis.

  • Symptom control
  • Symptomatically, patients usually complain of pruritus and fatigue. Currently, there is no a targeted treatment against fatigue in PSC. For pruritus related to PSC or any other cholestatic liver disease, cholestyramine, a bile acid sequestrant, has historically been used. It remains the first line followed by rifampin, opioid antagonists, and sertraline in respective order of preference. Addressing pruritus is considerably important as it can result in sleep disturbances, depression, or suicidality.

Monoclonal Antibodies as Potential Future Agents

There is a selective humanized monoclonal antibody to the α4β7 integrin expressed in lymphocytes and has been approved for the treatment of IBD. This integrin binds selectively to an adhesion molecule named MADCAM1 which-aside from being expressed in the intestines-is also expressed in the peribiliary plexus in certain liver diseases including PSC. By binding to α4β7 integrin, this antibody may inhibit abnormal lymphocyte trafficking into the liver and thereby prevent the cycle of hepatic inflammation and fibrosis that occurs in PSC.

There is also an FDA-approved monoclonal antibody against LOXL2, an enzyme that plays a central role in fibrinogenesis and is elevated in the liver of patients with PSC. It was shown to be safe with potential for anti-inflammatory or anti-fibrotic effects in preclinical studies.

Services at Creative Biolabs

Focusing on therapeutic antibodies and cell-based therapy development over 10 years, Creative Biolabs has advanced technologies, high-degree experts specialized in drug development, and experienced technicians committed to relative experiments for years. With all these irreplaceable advantages, we are confident in our services including but not limited to:

  • Monoclonal Antibody Development for PSC
  • Bispecific Antibody Development for PSC
  • Cell-based Therapy for PSC

With great potential, therapeutic antibodies are important as future agents for PSC. Creative Biolabs has extensive experience accumulated from every step we paid in practice. If you are interested in therapeutic antibodies and cell-based therapy development, please feel free to contact us for more information.

Reference

  1. Jiang, X.; Karlsen, T. H. Genetics of primary sclerosing cholangitis and pathophysiological implications. Nat Rev Gastroenterol Hepatol. 2017, 14(5): 279-295.

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