TECHNOLOGY
NEURON HEALING FOR BETTER LIVING
Dendrogenins are cholesterol derivatives which stimulate cell differentiation in the immune and nervous system and induce the growth of dendrites on dendritic cell and neuron precursors.
On that basis, Dendrogenix has developed this family for new therapies in therapeutic areas with unmet needs including hearing loss and neurological diseases.
A wide range of preclinical studies have shown that these compounds could provide therapeutic solutions for pathologies resulting from synaptic neuronal deficiency, such as presbycusis or neurodegenerative disorders, following a cerebral ischemia.
The lead compound - DX243 - is presently evaluated in a phase I clinical study to target presbycusis
Hearing loss can be subdivided into two broad categories:
Conductive hearing loss is characterized by the inability to mechanically transmit sound vibrations from the environment to the inner ear.
Conductive loss is due to disorders of the external and middle ears.
Sensorineural hearing loss is characterized by the inability to effectively transduce sound information into usable neural signals.
The majority of sensorineural loss is the result of disorders of the inner ear itself and is not directly related to dysfunction of the vestibulocochlear nerve.
Sensorineural hearing loss is the most common type of hearing loss. It occurs due to aging, exposure to loud noise, injury, disease, certain drugs (ototoxicity) and genetic conditions is a true sensorineural loss, in which both cochlear hair cells and, to a lesser extent, the spiral ganglion cells in the vestibulocochlear nerve can be affected.
Presbycusis, or age-related hearing loss, is a common cause of sensorineural hearing loss in adults worldwide. Presbycusis is a complex and multifactorial disorder characterized by symmetrical progressive loss of hearing over many years. It usually affects the high frequencies of hearing, although its presentation and clinical course can be variable. Presbycusis has a tremendous impact on the quality of life of millions of older individuals and is increasingly prevalent as the population ages.
The severity of the hearing loss is described as mild, moderate, severe, or profound. Regardless to these categories, different hearing devices (aids or implant) are appropriate for patients.
Although there are no strict criteria when hearing amplification should be recommended:
Hearing aids are generally indicated when high-frequency hearing thresholds reach 40 dB on an audiogram. A hearing aid carries sound from the environment to the ears and amplifies it.
Cochlear implants are used for patients with severe hearing loss that is not significantly improved with hearing aids.
The prevalence of hearing loss increases with age, with up to 80 percent of functionally significant hearing loss occurring in older adults. It is more common in males than females, possibly related to higher levels of noise exposure seen in this population.
The World Health Organization (WHO) estimates that in 2025 there will be 1.2 billion people over 60 years of age worldwide, with more than 500 million individuals who will suffer significant impairment from presbycusis.
There are no available FDA or EMA approved treatments to prevent or reverse presbycusis. Most patients with significant age-related hearing loss will benefit from use of hearing devices (hearing aids & hearing implants), these devices would only amplify the sound, not treat the condition. Hearing aids are sound amplifiers that detect sound and amplify frequencies which are useful for the perception of human speech. Cochlear implants are devices which detect the sound from the environment, convert it to electrical signals, and then send a signal to the internal electrode array of the implant, effectively bypassing the damaged hair cells to directly stimulate the auditory neurons.
This is the only solution to sensorineural hearing loss. It can’t be treated through medications and surgery for now. However, many patients have had negative experiences with hearing aids or have heard other patients' negative reactions to hearing aids.
Based on those numerous inconvenient and the low penetration of hearing aids solution, developing a drug treatment seems a right strategy to answer this unmet medical need.
The main worry for patients is that they will struggle to understand people in noisy environments. No approved medication is currently available, which could be used to treat this pathology. The only available options are electronic medical devices. A pharmaceutical treatment would make all the difference for millions of people.
There are no current treatments for hearing loss related to loss of auditory neurons. Most patients with significant age-related hearing loss will benefit from use of hearing devices (hearing aids & hearing implants. Many patients have had negative experiences with hearing aids or have heard other patients' negative reactions to hearing aids. The aid may also cause discomfort, and it is a cosmetic concern for many patients.
These devices would only amplify the sound, not treat the condition. There is strong evidence that DX243 has great potential as an effective therapeutic for the prevention and treatment of sensorineural hearing loss. Considering all the scientific data collected during the various proof-of-concept studies for DX243 and the lack of therapeutic options for hearing loss on the market, DX243 is a drug candidate with great potential to provide an innovative and effective solution for the prevention and treatment of hearing loss.
In order to meet the regulatory requirements for the start of clinical trials, numerous in vitro and in vivo safety studies (pharmacokinetics, absorption, distribution, metabolism, excretion and toxicology) have been successfully conducted with DX243. They demonstrate a strong safety profile.
This clinical trial marks a crucial stage in the development of new treatments for patients suffering from age-related hearing loss. The Phase 1 clinical study aims to evaluate the safety, tolerability and pharmacokinetics of DX243. It will be followed by Phase 2a, which will focus on patients suffering from mild age-related hearing loss.
Dendrogenix company, which specializes in the study and development of Dendrogenins, has announced the launch of its clinical trial, focusing on the treatment of presbycusis. Age-related hearing loss affects millions of people and is still treated exclusively by means of medical devices. Hair cell damage can be partially circumvented by the use of hearing aids and cochlear implants, there are no treatment options that target auditory neuron loss.
If the auditory neurons are lost or damaged, then the efficacy of these medical devices will not be high since the auditory neuron population will not be sufficient to send the sound signal from the cochlea to the brain. Considering that Dendrogenins could improve hearing level, impaired patients could directly benefit from the pharmaceutical effect and even patients who were not eligible for cochlear implants could recover enough neuronal connection to become implantable. DX243 therefore is unique and differs from all other existing technologies.
As mentioned previously, presbycusis is the first targeted market segment, although prevention of hearing loss associated with acoustic trauma and sudden-onset deafness are two therapeutic indications that will be targeted as second-line treatments. More importantly, the results of these studies could be used as such for the further development of the DX243 in other indications if no changes are made to the drug (same formulation, route of administration and dosage).
We are delighted to have initiated this clinical trial for Dendrogenins, as this major scientific breakthrough offers hope to so many people all over the world.
Dendrogenix' objective is also to evaluate the therapeutic potential of the Dendrogenins’ family in models of neurodegenerative diseases through its drug discovery platform.
Collaborative work involving Dendrogenix and the GIGA-Neurosciences (Prof. B. Malgrange's team) demonstrated that Dendrogenins restore the auditory nerve damaged by excitotoxic stress (excess glutamate).
Excitotoxic stress is associated with many neurodegenerative diseases including autism, cerebral ischemia, spinal cord injury, epilepsy and Alzheimer's disease. These pathologies currently remain without satisfactory therapeutic solutions.
Dendrogenix is working on the Dendrogenins family and produces other chemicals to be tested initially on in vitro (cellular models) to identify the most promising molecules (lead compound(s)).
Dendrogenix uses in vivo models to test the selected candidates and its mode of action in the pathology(ies) likely to better respond to the beneficial effects of Dendrogenins in neurology.
Founded in 2018, Dendrogenix develop first-in-class molecules, Dendrogenins, to address high unmet medical needs in hearing loss and neurology.
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