Delivery of pancreatic islets and beta cells to brain: a novel technology for treatment of neurodegenerative diseases
Innovative Products and Technologies
Technology Offer
Delivery of pancreatic islets and beta cells to brain: a novel technology for treatment of neurodegenerative diseases
- RAMOT at Tel Aviv University Ltd.
- From Israel
- Responsive
- Innovative Products and Technologies
Summary of the technology
Neurodegenerative disorders are among the most serious health problems facing modern society. Many disorders including Alzheimer's (AD) and Parkinson's (PD) disease occur as a result of loss of structure and function of neurons. Although tremendous efforts have been made in the treatment of these diseases, a long-term, effective therapy is still lacking. One of the most promising approaches for therapeutic intervention is the delivery of neurotrophic factors (NTFs) to the brain of patients with neurodegenerative disorders for neuron protection and neurogenesis. Abnormal insulin processing, insulin receptor defects or post-receptor defects can lead to CNS problems, including AD and Parkinson's disease. Recent clinical trials have indicated that intranasal delivery of the pancreatic hormone insulin to the olfactory system improved both memory performance and metabolic integrity of the brain in patients suffering from AD or mild cognitive impairment. Moreover, it has been suggested that insulin therapy allows correction of the decreased brain insulin levels and impaired glucose signaling associated with declining learning and memory of patients with various neurodegenerative diseases including AD and PD. It has been shown that pancreatic islets synthesize and secrete a combination of various hormones (insulin, glucagon and somatostatin) and neurotrophic factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophins 3 and 4. We suggest that such a combination of therapeutic agents will demonstrate significant cytoprotective and neuroregenerative potential. In the proposed project we intend to develop a platform for innovative cell-based therapy for various neurodegenerative disorders. This therapy is based on intracranial transplantation of pancreatic islets or beta cells, and potentially has several advantages compared to current technologies:
• Systematic delivery of a unique combination of therapeutic agents including pancreatic hormones and NTFs to the brain of patients with neurodegenerative disorders.
• Another advantage of this technology is that pancreatic islets are equipped with highly sophisticated mechanisms regulating the secretion of islet-derived therapeutic agents (NTFs and hormones) in accordance with the metabolic requirements of patients.
• Compared to stem cell-based transplantation, pancreatic islets are composed of mature adult cells which, in the past decades, have been safely transplanted in m
Project ID : 10-2013-550
Details of the Technology Offer
THE NEED
Altzhiemer's disease is one of the most studied pathologies in the world. It is also one of the most frustrating, as many of the drugs that reach late clinical trials fail due to low efficacy. In the last decade it is becoming clear that insulin, that plays an essential role in another world pandemic (Diabetes) plays a significant role in neurodegenerative diseases in general and in Altzhiemer's disease in particular. Growing evidences support the concept that Alzheimer’s disease, which is the most common cause of dementia in older adults, represents a metabolic disease with impaired brain glucose utilization and energy production. The term “Type III diabetes” was proposed for Alzheimer’s disease as a form of brain diabetes that has elements of both insulin resistance and insulin deficiency.
In the past number of years, in order to fight this insulin deficiency and resistance in the brain, researchers have been searching for ways to deliver insulin into the brain as Insulin delivery to the brain was shown to improve memory and cognition in patients with brain disorders (e.g. Alzheimer’s disease). However, a technology for safe, efficient and metabolically regulated insulin delivery to the brain is still not developed. To the best of our knowledge, direct delivery of insulin producing pancreatic islets to the brain has not yet been used as a therapeutic tool for treating cognitive dysfunctions.
TECHNOLOGY
In this project, we intend to overcome current limitations of insulin delivery to the brain using intracranially implantable miniature bio-hybrid device (brain implant) containing living insulin producing pancreatic islets. The brain implantation site is highly oxygenated and immune-privileged. Insulin release from islets is strictly regulated by metabolic signals (e.g. glucose).
The clinical size brain implant is placed in the subarachnoid cavity in the brain that is filled with cerebrospinal fluid (CSF). The pancreatic islets are isolated from immune system of the recipient by an alginate hydrogel and membrane permeable for insulin, glucose and oxygen.
POTENTIAL APPLICATION
Implantation of metabolically regulated Insulin secreting pancreatic Islets for the treatment of cognitive brain disorders
ADVANTAGES
• Most efficient insulin delivery to the brain
• Well oxygenated site of transplantation- important for the survival of the β cells
• Long term functionality of the transplant
• Easy insertion and simply removal and exchange of implant
PATENTS
US20130336938 A1- Granted Patent