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Gene Therapy Development for Alzheimer's Diseases


Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by age-related amyloid-beta (Aβ) deposition neurofibrillary tangles, and synapse and neuronal loss. Currently, only few drugs have been approved for the treatment of AD and impact the symptoms rather than disease progression. By the identification of genes that are related to AD, several gene therapy strategies for AD have been proposed, such as the use of adeno-associated virus 2 (AAV2) mediated nerve growth factor (NGF) gene transfer through the blood-brain barrier. Lentvirus mediated CRTC-1 overexpression in the hippocampus efficiently reverses Aβ-induced spatial learning and memory deficits. Empowered by first-class platforms and rich experience in the field of gene therapy, Creative Biolabs now provides one-stop custom-oriented service for your research to speed up the projects for academic and clinical purposes.

Overexpression of CRTC1 in the hippocampus of Alzheimer’s rats and Memory test Figure 1. Overexpression of CRTC1 in the hippocampus of Alzheimer's rats and Memory test (Furtado 2014)

Featured Services for AD Gene Therapy strategies

Generally, the accumulation of Aβ is the principal pathogenic event of AD and a growing body of evidence shows gene therapy-targeting Aβ holds great promise for reducing Aβ in the brain. It has reported that AAV vector encoding anti-Aβ monoclonal antibody can cause a significant decrease in Aβ levels in the brain of AD mice. At the same time, the AAV-mediated Aβ immunization has also provided the basis of a novel AD vaccination therapeutic strategy. Mounting evidence shows that expression levels of neprilysin efficiently degrades the Aβ peptides in AD patients. In preclinical study, the stereotaxic infusion of neprilysin encoding viral vectors into the hippocampus has been shown to decrease Aβ in AD-model mice. In a word, the modulation of the Aβ concentration in the brain by gene transfer may become a promising option for the AD treatment.

In previous research, it has been proved that nerve growth factor (NGF) enhances the function and survival of basal forebrain cholinergic neurons that are vulnerable in AD. Some groups have illustrated that efficacy of NGF gene delivery can improve the cerebral metabolism and cognition in AD patients without adverse events. In addition, the insulin-like growth factor 2 (IGF2) has also been found playing a critical role in memory consolidation in mice and AAV-mediated delivery of IGF2 the hippocampus of the AD mouse can promote dendritic spine formation, improve the behavioral deficits , restore normal hippocampal excitatory synaptic transmission and reduce amyloid levels.

Anti-inflammatory cytokines (IL-4, IL-10) can suppress neuroinflammation and play an emerging role as neurotransmitters, neuromodulators and neurohormones in the brain. More evidence suggests that the IL-4, IL-10 and CD74 gene delivery have therapeutic potential for AD treatment. Another factor closely connected with the development of AD is cholesterol metabolism that can increase the production and deposition of Aβ peptides. Holesterol acyltransferase 1 (ACAT1), the gene knockdown of the cholesteryl ester synthetic enzyme acyl-CoA, have shown benefits in mouse models of AD. Both the gene therapy based on the cytokines transfer and the genetic inactivation herald a new therapeutic frontier for AD.

Over years Creative Biolabs has won good reputation in the field of gene therapy and we are glad to share our technologies and experience to facilitate your projects. Please feel free to contact us for more details and our team will get back to you as soon as possible.

Reference

  1. Furtado, C., Santos, D., Kihara, A. and Paschon, V. (2014). TERAPIA GÊNICA RECUPERA MEMÓRIA DE RATOS COM ALZHEIMER: um novo passo em direção à cura. Nanocell News, 1(11).
  2. Destefani, A. (2017). Cell and Gene Therapies for Alzheimer's disease: a Review of Literature. Cancer therapy & Oncology International Journal, 3(1).
  3. Choong, C., Baba, K. and Mochizuki, H. (2015). Gene therapy for neurological disorders. Expert Opinion on Biological Therapy, 16(2), pp.143-159.

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