Immunotherapy for Stroke and Cognition in a Cerebral Amyloid Angiopathy Animal Model
Knowhow and Research output
Technology Offer
Immunotherapy for Stroke and Cognition in a Cerebral Amyloid Angiopathy Animal Model
- RAMOT at Tel Aviv University Ltd.
- From Israel
- Responsive
- Knowhow and Research output
Summary of the technology
Cerebral amyloid angiopathy (CAA) is due to amyloid accumulation in the vessel walls leading to hemorrhagic stroke, and cognitive impairment. There are no available treatments to specifically reduce the risk of CAA. In this research we aim to assess brain tissue damage and cognitive impairment resulting from CAA in animal model and to investigate a novel approach to immune therapy. Methods: We have shown that nasal vaccination with a proteosome adjuvant (Protollin) that is well tolerated in humans, decreases amyloid plaques in an Alzheimer’s disease mouse model. It was recently reported that an overexpression of TGF-?1 under the control of an astrocyte promoter GFAP in mice results in CAA. TGF-?1 mice were nasally treated with Protollin on a weekly basis starting at the age of 13 months for three months. Following treatment animals were subjected for MRI and cognition analysis. Results: Here we show that nasal Protollin activates perivascular macrophage and potently decreases vascular amyloid in TGF-?1 mice. Using MRI we found that while PBS treated animals showed a significant enlargement of the lateral ventricles area, Protollin prevents further brain damage and prevents pathological changes in the blood-brain barrier. Vascular risk factors have been found to be associated with vascular dementia. Using an object recognition test and Y-maze, we found significant improvement in cognition with the Protollin treated group. Interpretation :Our study demonstrates that activation of macrophages by Protollin is a novel approach to reduce microhemorrhage, prevent stroke and improve cognition in a model of cerebral amyloid angiopathy.
Project ID : 10-2011-259
Details of the Technology Offer
Cerebrovascular dysfunction is a fundamental part of the pathology of several neurodegenerative diseases and rated as one of the most prominent cause for dementia. Cerebral amyloid angiopathy (CAA) results in intra-parenchymal and subarachnoid bleeding, which is caused by cerebrovascular amyloid deposits and multiple infarcts, and can lead to hemorrhagic stroke and cognitive impairment (Greenberg et al. Stroke. 2004; 35:2616-2619; Frangione et al. Amyloid. 2001; 8 Suppl 1:36-42). The prevalence of CAA, estimated from autopsy series, is approximately 10% to 40% of the general elderly population (Greenberg et al. Stroke. 2004; 35:2616-2619). Although the most common form of cerebrovascular amyloid is Aβ-CAA, there are other proteins that have been linked to familial forms of CAA such as: APP, cystatin C, BRI, prion protein, gelsolin, and transthyretin (Burgermeister et al. Lessons from mouse models. Ann N Y Acad Sci. 2000; 903:307-316). Clinical interventions usually consist of blood pressure control (i.e., hypertension treatment) as well as avoidance of medications that increase systemic hemorrhage risk (e.g., aspirin). However, there are no current treatments to reduce amyloid pathology in CAA (Maia et al. J Neurol Sci. 2007; 257:23-30).
US Patent.
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