Periodic Reporting for period 2 - HOMEOBRAIN (Homeoproteins as novel therapies for neurodegenerative diseases)
Berichtszeitraum: 2023-11-01 bis 2024-10-31
With population living older, neurodegenerative diseases are becoming one of the biggest healthcare challenges. Among them, Amyotrophic Lateral Sclerosis (ALS) is a devastating and fast-progressing disease, affecting mature adults, that kills motor neurons of the spinal cord that control voluntary muscles, progressively leading to global paralysis and death (respiratory failure). The population of patients living with ALS at a given time (prevalence) is relatively small with about 200k patients worldwide, while the number of new patients diagnosed per year is rather high (between 2 and 9 per 100000, depending on the region). This apparent discrepancy is the result of the short life expectancy (average 2-5 years) of patients after diagnosis, as there is no effective treatment today that stops or slows down disease progression.
BrainEver is developing neurodegenerative disease-modifying therapies based on a family of human proteins, called Homeoprotein (HP). These well studied proteins are essential during the embryo development (organ modelling). The discovery that some of them continue to be active and contribute to the maintenance, repair and survival of specific cells in adults is the foundation of BrainEver. The first homeoprotein developed is Engrailed-1 (hEN1) that has been shown to specifically repair and rescue spinal motor neurons - those that degenerate in ALS- in preclinical models. Based on its homeoprotein properties established in animal models, hEN1 injected in the spinal canal, specifically reach the diseased neurons and is active for several months, potentially translating into few injections per year in patients. Being an essential physiological, it is also expected to be extremely well tolerated as already demonstrated in animals.
The potential of safely slowing down the disease will be determined in patients living with ALS in future clinical trials.
BrainEver is developing neurodegenerative disease-modifying therapies based on a family of human proteins, called Homeoprotein (HP). These well studied proteins are essential during the embryo development (organ modelling). The discovery that some of them continue to be active and contribute to the maintenance, repair and survival of specific cells in adults is the foundation of BrainEver. The first homeoprotein developed is Engrailed-1 (hEN1) that has been shown to specifically repair and rescue spinal motor neurons - those that degenerate in ALS- in preclinical models. Based on its homeoprotein properties established in animal models, hEN1 injected in the spinal canal, specifically reach the diseased neurons and is active for several months, potentially translating into few injections per year in patients. Being an essential physiological, it is also expected to be extremely well tolerated as already demonstrated in animals.
The potential of safely slowing down the disease will be determined in patients living with ALS in future clinical trials.
In 2023, an evaluation of a potential toxicity of hEN1 was conducted in animals, as a prerequisite required by health authorities to allow conduct of human clinical trials. The study to be conducted was previously discussed and agreed with the relevant Regulatory bodies. The effects of different high doses of hEN1, administered at two-week intervals were evaluated and compared to the injection of a solution without hEN1.
There was no behaviour, clinical or medical event to be reported during the study and the product showed an overall good tolerability profile.
Those data, as well as a first in human clinical study summary have been shared in 2024 with the Netherlands Regulatory Authorities during a advice consultation to have their recommendation before finalizing the clinical study protocol.
There was no behaviour, clinical or medical event to be reported during the study and the product showed an overall good tolerability profile.
Those data, as well as a first in human clinical study summary have been shared in 2024 with the Netherlands Regulatory Authorities during a advice consultation to have their recommendation before finalizing the clinical study protocol.
hEN1 is the first ever homeoprotein developed as a therapeutic. The homeoprotein family consists of about 300 members sharing great homology in their structure and cell signalling function. What differentiate them is the tissue in which they act and the cells they are acting on. The proof-of-concept demonstrating the capability of hEN1 to halt or slow down the progression of ALS in patients would open the field to other HPs for the treatment of other diseases. A second HP, OTX2, has already been identified as a candidate for the treatment of glaucoma and AMD.