Research

The only gene therapy for Alzheimer’s disease with a multifactorial approach

A gene therapy based on E2F4DN. A promising approach for a disease that affects 50 million people in the world and that has no effective treatment.

Alzheimer and gene therapy in two minutesWatch the video

The science behind our therapy

Neurons subjected to stress (excitotoxicity, trophic deprivation, oxidative stress, Aβ, …) increase the expression of the cell cycle regulators.
The reentry of the cell cycle leads to the replication of the DNA, tetraploidy and the neuropathological characteristics of Alzheimer’s disease.
Several cell cycle regulators are risk factors for Alzheimer’s disease. Amongst them is E2F4, a crucial protein for neuronal function.

Research carried out by the team at Tetraneuron have shown that in situations of stress, p38Map Kinase phosphorylates E2F4, inhibiting its function, which triggers the appearance of the different neuronal damage present in Alzheimer’s disease.
Tetraneuron’s therapy is in a development phase, based on the use of E2F4DN, a negative dominant form of E2F4 that cannot be phosphorylated. In this way, phosphorylation is prevented and neuronal tetraploidy is not triggered, resulting in improvements in the cognitive functions of Alzheimer mice models.

Lines of research

Tetraneuron is concentrating its research on E2F4, a cell cycle regulator extensively related to Alzheimer’s disease.

Therapy research

Research in biomarkers

TETRANEURON AAV-E2FADN, multifactorial gene therapy for Alzheimer’s disease

E2F4DN is a modified variant of E2F4 that cannot be phosphorylated. The blocking of this phosphorylation prevents the start of neuronal tetraploidy, restoring homeostasis and neuronal function in the brain.

TETRANEURON AAV-E2F4 is a safe product that is only expressed under the control of a neuronal promoter, improving several pathological mechanisms of Alzheimer’s disease.

We have developed a disruptive, highly innovative technology; patented in the United States, the European Union and Japan.

Research in biomarkers

Tetraneuron is working on the phosphorylation of E2F4 during the earliest stages of Alzheimer’s disease, analysing the presence of phosphorylated E2F4 in blood serum as an early biomarker for this disease.

This technology has been patented internationally.

Scientific articles

Pathological aspects of neuronal hyperploidization in Alzheimer’s disease evidenced by computer simulation (2020)

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Primary neurons can enter M-phase (2019)

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Cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons (2018)

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Neuronal tetraploidy in Alzheimer and Aging (2017)

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Neuronal tetraploidization in the cerebral cortex correlates with reduced cognition in mice and precedes and recapitulates Alzheimer’s-associated neuropathology (2017)

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Strand-specific CpG hemimethylation, a novel epigenetic modification functional for gene silencing (2017)

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Nerve Growth Factor-Induced Cell Cycle Reentry in Newborn Neurons Is Triggered by p38MAPK-Dependent E2F4 Phosphorylation (2012)

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Somatic tetraploidy in specific chick retinal ganglion cells induced by nerve growth factor (2010)

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Induction of cell death by endogenous nerve growth factor through its p75 receptor (1996)

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