Aloïse Mabondzo has been interested for some years in the pharmacological properties of certain purine derivatives, such as the attenuation of mechanisms involved in the pathogenesis of brain lesions observed in neurodegenerative diseases. In 2018, he filed a patent entitled "Purine Derivatives For Use As Medicament And For Use In Treating Neurodegenerative Or Neuro-Inflammatory Disorders" which aims to provide purine derivatives for the prevention and/or treatment of neurodegenerative disorders (Alzheimer's, Parkinson's, Huntington's, Amyotrophic Lateral Sclerosis, Down's Syndrome) and neuro-inflammation associated disorders.
That same year, A.Mabondzo began a collaboration with two leading American partners in the fields of brain injury pathogenesis and of the development of innovative strategy to study the passage of therapeutic molecules across the BBB: respectively, Dr. Barbara Stonestreet, professor of pediatrics, neonatologist at Women & Infants Hospital in Providence, Brown University (Rhode Island) and Dr. William A. Banks, professor of medicine at the University of Washington School of Medicine, Seattle.
In October 2019, Barbara Stonestreet and Aloise Mabondzo decide to submit a project to the NIH, as PI and Co-PI respectively, and also submit, in April 2020, a joint patent entitled "Purine Derivatives as Drugs for the Treatment of Neonatal Hypoxia-Ischemia Brain Injury and Related Diseases".
Finally, in February 2021, Aloïse Mabondzo receives the final acceptance of the NIH funding for his project with Barbara, an amount of $3M over 5 years, including $1M for her laboratory!
The project accepted today by the NIH aims to pursue the development of a promising drug candidate (BRT001) against neonatal hypoxic-ischemic encephalopathy (HIE) in newborns at or near term. A Mabondzo brings along two researchers from the Joliot institute, Fawzi Boumezbeur and Sébastien Mériaux (NeuroSpin), who will be involved in the monitoring of long-term changes in brain anatomy, vasculature and microstructure using in vivo MRI at ultra-high magnetic field in animals that recovered from neonatal HIE related brain injury with and without BRT001 treatment. This also demonstrates the capacity of Joliot researchers to develop strong transversal axes, on both major and global medical issues.
Contacts : Aloïse Mabondzo ; Isabelle Philippe
- Aloïse Mabondzo has been working for several years on the development of cellular models to study the permeability of the human blood-brain barrier (BBB) in order to predict the entry of drug candidates into the brain and to better understand its role in brain diseases. In 2019, he co-founded CERES BRAIN THERAPEUTICS, a company dedicated to the treatment of rare brain diseases, with an initial focus on the creatine transporter deficiency syndrome, an untreated neurological disease responsible for developmental delay, intellectual disability, pseudoautistic behaviors and seizures. CBT101, a creatine dodecyclic ester, is the company's first orphan drug candidate. It was approved in March 2021 by the European Medicines Agency and the FDA. This drug candidate has already demonstrated efficacy in a preclinical model of the disease.
- Neonatal hypoxic-ischemic encephalopathy : HIE is a severe brain injury resulting from a significant decrease in blood flow and oxygen to the brain at birth. Responsible for nearly one million deaths per year, or 24% of all newborn deaths worldwide, neonatal HIE is a major medical concern. Studies suggest a prevalence of between 11,000 and 88,000 cases in 2019 in developed countries and 2,444,000 in developing countries (Figure). Once the diagnosis is made, the newborn with HIE should be promptly managed to minimize the extent of brain damage and associated sequelae. The therapy focuses on limiting the extension of the brain lesions by hypothermia. To date, no curative treatment has been identified.