Epigenetic Reversal of Age-Associated Brain Disorders
Homeoproteins and neurodegenerative disorders

Neurodegeneration is linked to aging, even when of genetic origin, always resulting in neuronal death and in the loss of essential brain functions such as memory, sensory or motor transmission and adapted social behavior. This results in a significant deterioration of quality of life for the patients and their relatives.

Homeoproteins are transcription factors naturally expressed throughout life. Thanks to identified peptidic sequences, homeoproteins are secreted and internalized and can thus transfer between cells in vivo. During development, homeoprotein intercellular transfer influences cell migration and axon guidance whereas, at post-natal and adult periods, it controls cerebral cortex neuronal network plasticity (reviewed in Prochiantz & Di Nardo, 2015).

Furthermore, homeoproteins boost mitochondrial metabolism, participate in the maintenance of physiological epigenetic marks and limits the formation of DNA breaks which are a hallmark of aging.

The data confirming the role of distinct homeoproteins in the protection of specific neuronal populations support the idea that homeoprotein administration to patients with neuronal degeneration may protect the surviving neurons from death while increasing their physiological activity. The expected clinical outcome is a reversal of the symptoms with an amelioration of the condition of the patients.

The lead project is BREN01, the human Engrailed 1 that has been shown, in different animal models of Parkinson, to protect the surviving dopaminergic neurons from death while increasing their physiological activity. Indeed, Engrailed stops neuronal cell death, restores epigenetic marks and increases dopamine production in several animal models of the disease. (Sonnier et al, 2007; Alvarez-Fischer et al, 2011; Rekaik et al, 2015).

Engrailed 1 is also being evaluated in preclinical models of ALS (Amyotrophic Lateral Sclerosis) where it appears to protect motoneurons from death.

Other homeoproteins are being explored, based on their expression and physiological role in adult. 

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Company Strategy

Beside Engrailed 1 in Parkinson Disease and ALS, BrainEver is currently generating a pipeline of several drug candidates targeting other neurodegenerative diseases and ocular diseases.

The Company plans to establish clinical proof-of-concept for selected drug candidates. Leveraging its systematic approach to identify in vivo the potential of homeoproteins as therapeutic agent, BrainEver will allow developing next-generation targeted brain disease modifyer.

The company is excellently positioned to play a leading role in this field. Please contact info@brainever.com for any further information.