We are thrilled to announce our strategic collaboration with Paris Brain Institute to explore the potential of our cutting-edge cell macroencapsulation technology in treating metachromatic leukodystrophy (MLD). This partnership aims to combine Release Therapeutics' innovative technology with the Institute’s extensive expertise and research capabilities in neuroscience, marking a significant step forward towards finding effective treatments for this debilitating lysosomal storage disorder.
Metachromatic leukodystrophy (MLD) is a rare genetic disorder of the central and peripheral nervous systems that leads to progressive loss of myelin, a protective sheath that wraps around and insulates each nerve cell.
MLD is caused by an inherited deficiency in arylsulfatase A (ARSA), an enzyme located in lysosomes that helps break down fatty sulfatides in nerve cells. This deficiency leads to the accumulation of sulfatides in neuron and glial cells, which in turn leads to the degradation of myelin (demyelination) and the formation of scar tissue in its place, compromising the ability of nerves to conduct electrical impulses to the brain. The resulting symptoms of MLD include severe cognitive and motor decline (including difficulty swallowing and paralysis), seizures and loss of sensory functions.
Tragically, late infantile MLD, affecting young children aged 12 to 20 months, is the most common and rapidly progressing form of MLD, with most children unable to survive past the age of five.[1] Though pediatric patients with early, pre-symptomatic diagnosis are eligible for treatment with Libmeldy©, an ex vivo gene therapy recently approved by the FDA, symptomatic late infantile and early juvenile MLD patients are not eligible for treatment. Crucially, MLD is usually diagnosed after the appearance of symptoms, making it the most likely scenario that ‘parents lose a child to MLD to know to have a younger sibling tested for it – sacrificing a child to save another’. [2]
Release Therapeutics’ Research Collaboration with Paris Brain Institute to Target MLD
Release Therapeutics has recently formed a research collaboration with the distinguished Paris Brain Institute’s Innovation Unit for Gene and Cell Therapy (GENOV), in order to explore the potential of our cutting-edge cell macroencapsulation technology in the treatment of symptomatic MLD.
In a pilot research project, the GENOV Innovation Unit at the Paris Brain Institute implanted MLD mice with an analogue of our proprietary Myo-P device loaded with genetically engineered cells capable of delivering human ARSA enzymes to the central nervous system (CNS). At 6 months of age, the mice already presented symptoms of MLD and were divided into two groups to compare the effects of continuous human ARSA delivery with the analogue device, versus weekly intrathecal delivery of recombinant ARSA.
The results of the study were presented by Dr Françoise Piguet, Head of GENOV at the Paris Brain Institute, at the 20th WORLD Symposium for Lysosomal Storage Disorders (LSD) in February 2024, with the abstract published in a recent special issue of Molecular Genetics and Metabolism.[3]
The study, outlined in the symposium's abstract, highlights several key findings:
Continuous Delivery of ARSA: The analogue device was demonstrated to be capable of continuously delivering human ARSA enzyme, offering a significant advantage over weekly intrathecal injections, which are currently undergoing clinical evaluation in a Phase II study.
Biocompatibility and Efficacy: After three months of treatment, the analogue device continued to be well-tolerated, with the mice showing a significant reduction in sulfatide accumulation in the brain, improvement in neuroinflammation and reversal of disease progression. These findings suggest that our technology holds great promise in treating symptomatic MLD.
Targeting the Central Nervous System: Two constructs of genetically engineered ARSA-releasing cells were tested, revealing differential efficacies in targeting the central nervous system. In addition, two doses of encapsulated cells were assessed, indicating the optimal cell load for maximum therapeutic benefit.
Looking Ahead
The first of a series of planned joint research projects with Paris Brain Institute, this study and its outcomes signal that Release Therapeutics’ proprietary cell macroencapsulation technology is capable of delivering therapeutic proteins, including enzymes, where they are needed most in the CNS and beyond.
Importantly, the findings suggest that ours has the potential to become the first cell encapsulation technology for enzyme replacement therapy in children presenting symptoms of MLD, heralding a new era of hope for the families and children affected by this debilitating disorder.
Looking ahead at our research collaboration with the GENOV team at Paris Brain Institute, our intention is to build on these promising findings, as well as to explore the application of our technology for the treatment of additional lysosomal storage disorders and CNS malignancies.
Stay tuned for the latest updates on our research collaboration and innovation.
The Release Tx team
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