Eithan Galun MD, and Jonathan H. Axelrod PhD, The Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital.
Background
Acute renal failure (ARF) results when that the kidneys suddenly stop working. Acute kidney failure happens rapidly. The build up of toxic substances normally removed from the body by the kidneys can cause dangerous health problems. ARF is a major contributor to morbidity and mortality in hospitalized patients and the mortality of ARF remain high despite advances in supportive care. Epidemiologic studies suggest that ARF complicates up to one fourth of intensive care unit (ICU) admissions.
Medical Need: Approximately half of the ARF cases require hemodialysis or medicines to supplement lost kidney function. There are no established effective drug therapies, and dialysis may promote renal injury. Many agents [e.g., mannitol, furosemide, dopamine, atrial natriuretic Peptide, Insulin-like Growth Factor, thyroid hormone, etc.] are effective in animal models but ineffective in treating or preventing human ARF.
It is therefore of utmost importance to find new modes of treatment for ARF that restore the renal function and increase the quality of life by avoiding the dependence on dialysis.
Market
In a recent study of hospitalized Medicare patients in the United States, the overall incidence rate of ARF was 23.8 cases per 1000 discharges, with rates increasing by approximately 11 percent per year. In a multinational study in 23 countries, 6 percent of critically ill patients admitted had ARF during their ICU stay. Overall hospital mortality was 60 percent; dialysis dependency at hospital discharge was 14 percent for survivors. ARF is treated with continuous renal replacement therapy (RRT; cost: $6000 per week), or intermittent hemodialysis (cost: $1600 per week).
The Innovation
The induction of interleukin-6 (IL-6) expression has been observed during the development of ARF both in humans and in experimental animal models. IL-6 activates intracellular pathways via the gp130 receptor. Using two animal models of ARF in mice, the inventors have established a critical role for IL-6 and gp130 signaling in two apparently opposing functions inherent to ARF. They found that an IL-6 mediated inflammatory response contributes towards the generation of renal injury; however, also demonstrated that gp130 signaling mediates the induction of a protective response to renal injury. Furthermore, the inventors demonstrated that activation of gp130 trans-signaling by the administration of HYPER-IL-6, a chimeric protein, constructed from the human IL-6 protein fused to a truncated form of its receptor, prevents the onset of ARF and enhances survival.
R&D Program
ARF is mostly due to development of acute tubular necrosis (ATN). Research will focus on the understanding of IL-6 signaling and the process called transsignaling in ARF pathophysiological principles and the pathways of ATN for the development of potential means of treatment and prevention of renal injury.
Milestones:
- Influencing the balance of IL-6 signaling and trans-signaling through the use of designer cytokines such as HYPER-IL-6 that provide a novel therapeutic strategy for the treatment of ARF.
- Proof-of-Concept of the therapeutic potential of designer cytokines; obtaining full in vivo and in vitro pre-clinical data using animal models..
- Understanding and model for mechanism of action.
Contact
Yuval Kupitz,
Business Development, Pharmaceuticals
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
