Hepatocyte Microbeads for Acute Liver Failure

Summary

Acute Liver Failure in children is associated with high mortality without liver transplantation. In addition, donor organ shortage makes it difficult to provide this treatment to every potential patient. Liver transplantation is life-saving but it carries the risk of major surgery and complications from lifelong anti-rejection drugs to suppress the immune system. If bridged across the immediate crisis following acute liver failure, the immense regenerative potential of the liver means that the patient's own liver may 're-grow'. This period is very time sensitive. Unfortunately, if the vital synthetic and detoxification function of the liver is not provided, the patient will often die before the liver can re-grow. Transplantation of liver cells (hepatocytes) can provide this 'bridge' with considerable advantages over whole organ transplantation. Firstly, hepatocytes are derived from donor livers which are otherwise unsuitable for transplantation. Secondly, unlike whole organs, they can be frozen and stored, thus act as an 'off the shelf' treatment. Thirdly, the technique of hepatocyte transplantation within microbeads coated with alginate (a gel originating from seaweed) and infused into the abdominal cavity is much less invasive than liver transplantation. Finally, the alginate protects the cells against the body's immune system, avoiding the need for immunosuppressive drugs and the associated major risks. Furthermore, preclinical work in King's College Hospital has shown that the addition of support cells called mesenchymal stromal cells (MSCs), can significantly improve the ability of hepatocytes to survive and function within the alginate microbead. The HELP trial is a Phase 1/2 safety and tolerability study of infusion of HMB002 (an optimal combination of hepatocytes and mesenchymal stromal cells put together in peptide-alginate microbeads) into paediatric patients with acute liver failure. This novel cellular therapy may act as a bridge treatment to liver transplant or lead to regeneration of the native liver.

Timeline

Start

2022-09

Primary completion

2025-11

Completion

2026-05

Drugs

Indications