Eithan Galun MD, The Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital.
Background
Unlike other mammalian organs, the liver, after partial resection or massive injury, can rapidly regenerate and regain its original size, structure and function. Regeneration is a complex and highly ordered process involving multiple intra- and extra-cellular pathways and signals. Signaling molecules and transcription factors have been identified that are necessary for the onset of hepatogenesis. Cytokines and growth factors have been identified to serve as important signals controlling initiation and progression of hepatocyte replication as well as the termination of this process once the liver organ has reached certain level of growth.
Medical Need: Important advances have been made in understanding the key cellular and molecular players that drive liver development and regeneration, however, many questions remain unanswered. Major goals for research of liver regeneration are to fully define the molecular and cellular mechanisms underlying these processes in health and disease and to apply these findings in the development of improved therapies for liver disease.
Market
25 million Americans are suffering from liver disease. Chronic hepatitis B affects approximately 350 million people worldwide; it is the most common serious liver infection in the world that can cause liver failure, cirrhosis (scarring), liver cancer and death. Alcohol abuse and drug overdoses result in liver disease. There are only limited treatment options, such as medicines for some liver diseases. Some treat only the complications; others only delay the need for a transplant. Liver transplantation offers an acceptable treatment for many forms of end-stage liver disease. However, liver transplant is not a mass treatment for liver diseases due to the high price of liver transplants and follow up costs and a low number of donor organs.
The Innovation
In the liver, interleukin-6 (IL-6) is an important factor for the normal progression of tissue regeneration following injury. The inventors have shown that treatment of animals with administration of Hyper-IL-6, a chimeric protein, constructed from the human IL-6 protein fused to a truncated form of its receptor, as opposed to IL-6, dramatically enhances hepatocyte proliferation and significantly enhances survival following the induction of liver injury. HIL- 6, in contrast to IL-6, cooperates synergistically with hepatocyte growth factor (HGF) to induce hepatocytes proliferation in the absence of prior liver damage. Furthermore, the delivery of HIL-6 via an adenoviral (Ad) vector based gene therapy strategy can also be used to treat acute liver failure, perhaps with even greater efficiency than by protein therapy.
R&D Program
Research will investigate the mechanism by which HIL-6 protein therapy and adenoviral vector encoded HIL-6 delivery acts to enhance liver regeneration following injury. Applications investigated are:
1) Utility in treatment of fulminant hepatic failure
2) Enhancement of retroviral vector mediated in vivo gene therapy.
Milestones:
- Use of designer cytokines such as HIL-6 and cytokine combinations as novel therapeutic strategy to enhance liver regeneration.
- Proof-of-Concept and obtaining full in vivo and in vitro pre-clinical data using animal models.
- Establishment of initial safety (toxicology) and pharmacological profiles for candidate cytokines.
- Understanding and model for mechanism of action.
Contact
Yuval Kupitz,
Business Development, Pharmaceuticals
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
