Recent therapeutic approaches to cystathionine beta-synthase-deficient homocystinuria.

Abstract

Cystathionine beta-synthase (CBS)-deficient homocystinuria (HCU) is the most common inborn error of sulfur amino acid metabolism. The pyridoxine non-responsive form of the disease manifests itself by massively increasing plasma and tissue concentrations of homocysteine, a toxic intermediate of methionine metabolism that is thought to be the major cause of clinical complications including skeletal deformities, connective tissue defects, thromboembolism and cognitive impairment. The current standard of care involves significant dietary interventions that, despite being effective, often adversely affect quality of life of HCU patients, leading to poor adherence to therapy and inadequate biochemical control with clinical complications. In recent years, the unmet need for better therapeutic options has resulted in development of novel enzyme and gene therapies and exploration of pharmacological approaches to rescue CBS folding defects caused by missense pathogenic mutations. Here, we review scientific evidence and current state of affairs in development of recent approaches to treat HCU.

• Authors: Tomas Majtan, Viktor Kožich, Warren D Kruger
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 180 Issue 3 Pg. 264-278 (02 2023) ISSN: 1476-5381 [Electronic] England
• PMID: 36417581 (Publication Type: Journal Article, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The British Pharmacological Society.

Chemical References

• Cystathionine beta-Synthase

Topics

• Humans
• Homocystinuria (drug therapy, genetics, metabolism)
• Cystathionine beta-Synthase (genetics, metabolism)
• Quality of Life
• Thromboembolism
• Mutation, Missense