Assoc. Prof. Konstantin Bloch – Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University
Prof. Pnina Vardi – Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University
Prof. Oded Shoseyov – Plant Sciences and Genetics in Agriculture – Hebrew University
|Keywords||Alzheimer’s disease, brain insulin resistance, brain implant, pancreatic islets|
|Current development stage||For medical device: TRL4 – Proof-of-concept and safety of candidate devices/systems demonstrated in defined laboratory/animal models.|
|Collaboration Opportunity||Sponsored Research with an option to License Research Results|
The researchers developed a biocompatible brain implant containing cells secreting insulin for safe and efficient treatment of Alzheimer’s disease dementia and other cognitive disorders associated with brain insulin resistance and deficiency.
The prevalence of Alzheimer’s disease (AD) is significant and growing worldwide. Currently, specific treatments for AD is still a topic of ongoing research and debate. However, as research into AD progresses, there is growing interest in exploring potential therapies that could target insulin resistance in the brain.
Insulin in the brain has important regulatory effects on cognition. Accumulating evidence suggests that AD dementia is associated with impaired brain insulin signaling. The term “Type 3 diabetes” has been proposed for sporadic AD as a form of “brain diabetes” characterized by elements of both brain insulin resistance and insulin deficiency.
Studies in both humans and animal models have confirmed that insulin delivery to the brain is a promising anti-dementia therapy targeting aberrant insulin signaling in the brain. There are multiple therapeutic routes to deliver exogenous insulin to the brain such as intracerebroventricular, intravenous, intranasal and ocular administration. Currently, only the intranasal route is clinically relevant and was tested in clinical trials. However, all these routes cannot provide both efficient and safe delivery of exogenous insulin to the brain. The main reasons for that are problems of crossing blood-brain barriers, altering peripheral insulin levels, rapid clearance and poor penetration of insulin in the brain, and high-risk invasive insulin administration.
The research team developed a proprietary bio-hybrid device containing insulin-producing pancreatic islets/cells for minimally invasive implantation into cranial or thecal cerebrospinal fluid (CSF) of patients suffering from AD dementia. The implanted device could potentially overcome brain insulin resistance associated with development of dementia in AD patients.
Recently, the researchers demonstrated that intracranial delivery of a small number of living pancreatic islets into CSF significantly ameliorated cognitive dysfunctions in a rat model of AD dementia and increased concentration of insulin in the brain. The CSF implanted islets can function for a long-term period and do not alter peripheral glucose homeostasis.
This novel bio-hybrid device would provide:
- protection of implanted cells from immune responses
- optimal micro-environment for the implanted islets/cells
- bypassing the blood-brain barriers for insulin
- therapeutic level of insulin in the brain
- minimally invasive implantation of flexible hydrogel-based device, avoiding brain injury
- improved cognitive functions
The researchers developed an implant (size about 10 x 1 mm), loaded with insulin secreting pancreatic islets that can efficiently and safely delivery insulin into the brain. Using a minimally invasive and commonly used surgery, the implant can be inserted into the cranial or thecal CSF, avoiding brain injury.
Figure. The implant design and in vitro biological testing: (A) Islets immobilized in the device; (B) Glucose stimulated insulin secretion from islets immobilized in the device and naked islets, n=5
In addition to AD dementia, this technology may be applied for overcoming brain insulin resistance associated with different brain disorders, such as Parkinson’s and Huntington’s diseases, schizophrenia and autism, major depression, and traumatic brain injury.
The researchers are interested in partnering with a commercial entity to further develop this technology and then take a license to the technology or establish a startup company.
Patents and Publications
- Submitted provisional patent application (Yissum Ref # 6991; 2023).
- Therapeutic effects of intracranially transplanted islets using different animal models were published in leading journals.
- Bloch K, Gil-Ad I, Vanichkin A, Hornfeld SH, Taler M, Dar S, Azarov D, Vardi P, Weizman A. (2018) Intracranial Transplantation of Pancreatic Islets Attenuates Cognitive and Peripheral Metabolic Dysfunctions in a Rat Model of Sporadic Alzheimer’s Disease. J Alzheimers Dis. 2018; doi: 10.3233/JAD-180623
- Bloch K, Hornfeld SH, Dar S, Vanichkin A, Gil-Ad I, Vardi P, Weizman A. (2020) Long-term effects of intracranial islet grafting on cognitive functioning in a rat metabolic model of sporadic Alzheimer’s disease-like dementia. PLoS ONE 15(1): e0227879. https://doi.org/10.1371/journal.pone.0227879