Associate Professor, Sackler Faculty of Medicine, Tel Aviv University, Israel

Konstantin Bloch, PhD is head of research team at the Felsenstein Medical Research Center and associate professor at the Sackler Faculty of Medicine, Tel-Aviv University, Israel. Dr. Bloch is an expert in the field of pancreatic islet transplantation. He is the scientific co-founder of the Beta-O2 Technologies, a biomedical company developing a highly oxygenated implantable bio-artificial pancreas for treatment of type 1 diabetes (currently in Phase I/II). Recently, his team developed a proprietary technology of bioengineered insulin delivery to the brain for treatment of Alzheimer's disease.

Speech Title: Bioengineered insulin delivery to the brain for treatment of Alzheimer's disease

Background: Alzheimer’s disease (AD) dementia is often associated with brain insulin resistance and peripheral metabolic dysfunctions. Recently, we showed a high efficacy of insulin delivery to the rat brain using intracranially implanted pancreatic islets encapsulated in alginate hydrogel. In the current study, we studied long-termed effect of intracranially grafted islets on cognitive and peripheral metabolic dysfunctions in a rat model of sporadic AD.

Methods: AD-like dementia associated with obesity was induced in inbred Lewis rats using a single intracerebroventricular injection of streptozotocin (icv-STZ). Two months after icv-STZ, a small number of syngeneic islets (100 islets/recipient) was transplanted in the cranial subarachnoid cavity of icv-STZ rats. At six months after islet transplantation, cognitive functions and peripheral metabolism were studied.

Results: Six months after islet transplantation, grafted islets were viable, showed intact morphology and intensive staining for insulin, glucagon and glucose transported 2. Insulin content in the brain of grafted rats was significantly higher compered to non-transplanted animals. Peripheral glucose tolerance was intact in all tested groups. In the Morris water maze test, spatial learning and memory of islet transplanted icv-STZ rats were significantly improved compared to sham-operated icv-STZ animals.

Conclusions: Intracranial islet transplantation attenuates cognitive decline without alteration of peripheral glucose homeostasis in a rat model of sporadic AD. Efficient and metabolically regulated islet-based insulin delivery to the brain provides a novel approach for cell therapy of AD.