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Treating Genetic Disorders of the CNS without Gene Therapy (or what we’ve been up to here at Release Therapeutics)

Release Therapeutics (formerly “MaxiVax”) has strategically pivoted its focus towards treating disorders of the central nervous system (CNS) driven by the remarkable progress we have achieved with our cutting-edge proprietary technology. Innovating at the nexus of biotech and MedTech, we have evolved our cell encapsulation technology to deliver potent therapeutic proteins beyond the blood-brain barrier. Integrating an implantable minimally invasive bioreactor loaded with genetically-engineered human myoblast cells for targeted long-term protein delivery to the brain, our innovation promises a new era of effective and sustained treatment for diseases of the CNS.

Therapeutic proteins (such as cytokines, antibodies, enzymes, antigens) hold incredible potential in the treatment of CNS disorders, including genetic, oncological, and neurodegenerative conditions. These proteins can target specific pathways and mechanisms involved in CNS disease progression, offering targeted treatment options that traditional small molecule drugs often cannot achieve. The specificity and effectiveness of therapeutic proteins make them an invaluable tool in the fight against CNS diseases.

However, the application of protein-based therapeutics in treating CNS diseases continues to face significant challenges. The key obstacle is the blood-brain barrier (BBB), a highly-selective, semi-permeable membrane that regulates the passage of large and small molecules into the brain tissue, including therapeutic macromolecules.[1] The physical properties of therapeutic proteins, including their size, tensioactivity, and lipophilicity, make it challenging for them to pass through the BBB and reach their target sites within the CNS.

Release Tx’s Solution: A Cell Macroencapsulation Technology

At Release Therapeutics, we have developed a cutting-edge solution to these challenges with a proprietary technology specifically designed for delivering therapeutic proteins beyond the BBB. Consisting of an implantable macroencapsulation device, no larger than a pin, and a stable cell line that can be genetically modified to produce various proteins, our technology is the first to be designed for therapeutic protein delivery by cell macroencapsulation to the human CNS, marking a tremendous advancement in the field of encapsulated cell technology.

Release Therapeutics’ new-generation Myo-P® device is a versatile small hollow fibre device capable of immobilising cell lines genetically-engineered to produce diverse therapeutic proteins within a semi-permeable membrane (cell encapsulation).[2] The device’s biocompatible membrane allows the sustained passage of highly potent therapeutic proteins into the brain while protecting the encapsulated cells from the host’s immune cells. The device is easily implanted and retrieved without invasive surgical procedures, promising to enhance the efficacy and safety of encapsulated cell therapy in the CNS.

Synergising with the Myo-P device, our proprietary cell line from genetically-engineered human myoblasts can be modified to produce various therapeutic proteins, including cytokines, monoclonal antibodies, and viral antigens.[3] The cell line, designed to survive and proliferate indefinitely in culture (immortalisation), has demonstrated stable release of proteins in vitro for a period of more than two years. Together, these complementary pillars of our technology hold the transformative potential to revolutionise the treatment of CNS diseases by providing precise long-term delivery of therapeutic proteins directly to the brain.

Treating Genetic Disorders of the CNS without Gene Therapy

Offering significant advantages over gene therapy for the treatment of CNS diseases, including genetic disorders of the CNS, the evolution of our cutting-edge technology has been instrumental in Release Therapeutics’ decision to shift our strategic focus to the CNS.

Simply put, gene therapy involves replacing, deactivating, or editing defective genes in human cells that give rise to disease, aiming to restore the normal functioning of cells and tissues. This method encompasses the administration of biologics to alter a genetic sequence to enable the production of therapeutic proteins within the patient's own cells, holding considerable promise in treating CNS disorders—in particular, addressing the root cause of genetic disorders of the brain and spinal cord.[4] 

By contrast, cell encapsulation technology involves immobilising and isolating genetically-engineered cells capable of releasing therapeutics within a semi-permeable membrane, allowing the targeted delivery of therapeutics across that membrane over a longer period.

Release Therapeutics’ technology promises a safer alternative to gene therapy for CNS disorders, first and foremost because gene therapy often involves introducing permanent changes to the patient’s DNA, making it challenging to reverse or adjust the therapy in the case of an adverse event. By contrast, our macroencapsulation technology can be easily replaced or retrieved (in fact, also a major biosafety improvement over microcapsules), which is particularly important in CNS disorders where precise control over therapeutic interventions is critical. A related advantage is that our technology eliminates the risk of insertional mutagenesis and related malignancies, which can be a cause for concern when it comes to altering a patient’s genes.[5] Potential systemic exposure to genetic alterations and their off-target effects are avoided with cell encapsulation, which can provide localised treatment directly to the affected area of the brain. In addition, whereas the use of viral vectors with in vivo gene therapy can provoke an immune response in the CNS, our technology is optimised to limit immune reactions. Myoblast cells are associated with a reduced risk of eliciting immune response, while the Myo-P device’s semi-permeable membrane is immuno-isolating.

We have good reason to believe, moreover, that our technology will offer efficacy and scalability advantages compared to gene therapy and other encapsulated cell-based technologies to serve patients with CNS disorders. The stability and longevity of our myoblast cell line, coupled with its proven ability to deliver high yields of diverse therapeutic proteins over long durations without significant decline (e.g. GM-CSF cytokines and anti-CD20 and anti-CTLA-4 antibodies), offers the opportunity to treat chronic conditions over extended periods while maintaining efficacy. Our state-of-the-art macroencapsulation technology equally protects the cell lines from unfavourable conditions, washout, shear, and immunological rejection, enabling continuous release of therapeutics to the brain (thus we are now “Release Therapeutics”). The results from our first CNS animal models will be shared publicly soon.

In terms of scalability, our novel myoblast cell line can be efficiently frozen, stored, and thawed, limiting the challenges imposed by the manufacturing and supply of encapsulated cell-based therapeutic products. As mentioned above, our myoblast cell lines are immortalised and can be genetically engineered to deliver a broad range of protein interests, while the Myo-P implantable device is capable of encapsulating different cell lines, making ours a platform technology. This flexibility enables us to address a wide range of CNS diseases with different therapeutic protein requirements. Whether it's targeting specific genetic mutations or addressing oncological conditions, our technology can be tailored to meet the unique needs of each patient.

In particular, Release Therapeutics’ pipeline now prioritises the development of our proprietary technology to treat rare and serious lysosomal storage disorders, in which patients have very limited treatment options. Our lead programme in Metachromatic Leukodystrophy (MLD) — a rare genetic disorder that leads to progressive loss of myelin in the central and peripheral nervous system and typically affects young children — is currently in preclinical development. Developments in additional lysosomal storage disorders, CNS malignancies, and neurodegenerative diseases are scheduled to follow shortly.

Transforming the Treatment Landscape for CNS Disorders

The strategic pivot of our technology to treating CNS diseases heralds a groundbreaking advancement in this field. Integrating an implantable biocompatible macroencapsulation device with genetically-engineered myoblast cell lines for the targeted delivery of potent therapeutic proteins to the brain, Release Therapeutics has developed a technology that overcomes the limitations of traditional protein-based therapeutics and offers a safer and more scalable alternative to gene therapy with the potential to transform the treatment landscape for CNS diseases.

Our technology enables us to address the root causes of CNS disorders without altering the patient’s genes and deliver therapeutic proteins where they are needed most, opening up a horizon of possibilities where we can make a significant impact on the lives of patients.

As we continue to advance our technology and expand its applications, our research and development efforts are focused on further optimising our technology, exploring new therapeutic proteins, and expanding our pipeline to treat additional CNS disorders. We are also dedicated to collaborating with healthcare professionals, researchers and regulatory authorities to ensure the safe and effective implementation of our technology. By fostering partnerships and sharing knowledge, we aim to accelerate the development and adoption of our innovative therapies, ultimately benefiting patients worldwide.

With our cutting-edge technology, we are poised to make a significant impact on the future of CNS disease treatment and bring hope to patients and their families around the world.

Stay tuned for our latest developments — they’re worth the wait!

The Release Tx team

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