Alzheimer's Disease (AD) is a progressive neurodegenerative disorder and the leading cause of Dementia, ranking 7th among global causes of death. It is defined by the accumulation of abnormal proteins, including extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFT) formed by hyperphosphorylated tau protein. Normally, tau protein helps stabilize axonal microtubules, which are vital for intracellular transport. In AD, these pathological changes impair neuronal function and connectivity, leading to cell death and brain atrophy.
deaths due to Alzheimer's Disease and Dementia account for approximately 3.9% total deaths according to the most recent data.
There are 0 patients worldwide.
Estimated to reach 0 by 2050.
The "Lethe" project aims to propose a new therapeutic approach for the treatment and management of Alzheimer's Disease. By targeting the dephosphorylation of tau proteins, we increase the chances of halting the disease and reversing the underlying neurodegenerative course. As the Patras Medicine 2024 Team, our mission is to offer hope and support to patients and their families.
Utilizing the tools of Synthetic Biology, we used modified AAV-carrying exosomes as carriers of microRNA-195. The reduction of microRNA-195 levels within the cell is linked to various pathological processes of the disease, such as reduced activity of the phosphatase PP2A, an enzyme responsible for the process of tau protein dephosphorylation. The AAV-carrying exosomes interact with the surface of the patient’s target nerve cells and release AAVs that express microRNA-195, which can increase the activity of PP2A phosphatase and promote the dephosphorylation of tau proteins.
Exosomes are extracellular vesicles produced by normal cells, facilitating intercellular communication and waste elimination to maintain intracellular homeostasis. They also possess key advantages as drug carriers, supporting their potential use in Alzheimer’s Disease treatment.
Micro-RNAs are small, non-coding RNA molecules, typically 20-23 nucleotides long. MicroRNA-195 is closely linked to Alzheimer’s Disease, with its downregulation associated with increased AD pathology.
AAVs are ideal vectors for gene therapy and are non-pathogenic to humans. Our project utilizes AAV-based therapy to deliver microRNA-195 to neurons in Alzheimer's patients, using a specially designed vector cassette with the microRNA-195 DNA sequence.