Precision Neuroprotection for Multiple Sclerosis and Alzheimer's Disease
Neurodegenerative diseases like MS and Alzheimer’s Disease are characterized by inflammation in the central nervous system (CNS) that leads to neuronal damage and cognitive impairments. Most treatments rely on blanket immunosuppression to tamp down on the inflammation and slow disease progression, but fail to address the actual source of the disease – neuronal damage. At Bivium Biosciences, we are flipping the script and pioneering next-generation neuroprotective therapies that target the root causes of neurodegeneration.
Brief Overview
Unmet Medical Need
Many current treatments for neurodegenerative disorders such as Multiple Sclerosis or Alzheimer’s focus on blanket immuno-suppression and often fail to address the root cause of the disease. As a result, remissions are short-lived and relapse is common.
Our Crucial Insights
Recent work from our group has identified key therapeutic entry points within the neuronal injury cascade, allowing for strategic and precise targeting of this pathway rather than relying on non-specific treatments.
Our Therapeutic Strategy
Using nanobody-based therapeutics, we are able to capitalize on this discovery and strategically block key drivers of neuronal injury in the central nervous system with precision and purpose, blocking further neurodegeneration and protecting brain function.
Understanding Our Science
Foundational to our approach is the biological role of myelin and glutamate in our CNS. So, in order to fully grasp the differentiated nature of our therapeutic strategy, we must first lay some groundwork.
1. The Role of Myelin in Neuronal Function
A specialized cell type in our central nervous system called Oligodendrocytes (yellow cell) produce myelin, a multilayered insulating sheath that coats axons (long region of neuron – green cell) and promotes rapid and efficient nerve signal conduction. Stable myelin coating is essential for proper neuronal function.
2. The Essential Role of Glutamate
Another highly important component of our central nervous system is a molecule called glutamate (green molecule). This is normally produced by immune cells (purple cells) and it plays a critical role as the brain’s main neurotransmitter, facilitating communication between neurons and supporting essential functions like learning and memory.
3. The Dark Side of Glutamate
In neurodegenerative disorders like multiple sclerosis and Alzheimer’s, aberrant immune cell activity in the brain leads to excessive glutamate release. This elevated glutamate overstimulates receptors on oligodendrocytes, triggering excitotoxicity—a process that can eventually lead to cell death. As oligodendrocytes die, myelin is lost, impairing neuronal function and leading to further neurodegeneration.
Current Treatments are Insufficient
The following slideshow provides a concise overview of our scientific rationale and introduces our unique therapeutic approach.
Part I: The Role of Myelin In Neuronal Function
A specialized cell type in our central nervous system called Oligodendrocytes (yellow cell) produce myelin, a multilayered insulating sheath that coats axons (long region of neuron – green cell) and promotes rapid and efficient nerve signal conduction. Stable myelin coating is essential for proper neuronal function.
Part II: The Role of Glutamate In Neuronal Function
Another highly important component of our central nervous system is a molecule called glutamate (green molecule). This is normally produced by immune cells (purple cells) and it plays a critical role as the brain’s main neurotransmitter, facilitating communication between neurons and supporting essential functions like learning and memory.
Part III: Excessive Glutamate Causes Excitotoxicity
In neurodegenerative disorders like multiple sclerosis and Alzheimer’s, aberrant immune cell activity in the brain leads to excessive glutamate release. This elevated glutamate overstimulates receptors on oligodendrocytes, triggering excitotoxicity—a process that can eventually lead to cell death. As oligodendrocytes die, myelin is lost, impairing neuronal function and leading to further neurodegeneration.
Part IV: Current Treatment Strategies Are Insufficient
Due to its critical role in proper neuronal function, simply blocking glutamate signaling is not feasible. So, treatments tend to focus on widescale immunosuppression in an attempt to “tamp down” on inflammation in the brain. Clinical results are modest with short remissions and almost inevitable relapses. This can be explain by recent findings from our group that shows, even after inflammation subsides, glutamate-induced neuronal injury persists.
Part V: We Have Identified A Novel Therapeutic Entry Point
Recent research from our group has identified a molecule on oligodendrocytes that senses pathological glutamate, driving excitotoxicity without affecting normal signaling. Genetic deletion of this subunit preserved myelin, protected axons, and prevented neurodegeneration in preclinical models of Multiple Sclerosis. Importantly, removing the subunit did not impair normal glutamate signaling or neuronal function, marking it as an excellent therapeutic candidate.
Our Therapeutic Approach
At Bivium, we are taking a two-pronged approach to combatting neuronal injury in neurodegeneration, blocking both the source of pathological glutamate and it’s destination on oligodendrocytes.
1. Blocking The Source
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2. Blocking The Destination
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Why
Nanobodies?
Nanobody therapeutics offer a groundbreaking solution for treating neurological diseases by overcoming the challenges of drug delivery and specificity. Their small size allows them to cross the blood-brain barrier more effectively than traditional antibodies, while their high specificity ensures precise targeting of disease mechanisms, minimizing off-target effects.
Additionally, unlike small molecules, which are prone to poor pharmacokinetics and off-target side effects, nanobodies combine ease of development with exceptional precision. This makes them uniquely suited for addressing the intricate signaling pathways involved in neurodegeneration, providing a powerful and innovative approach to combat these devastating diseases.
At Bivium Biosciences, our mission is to revolutionize the treatment of neurodegenerative diseases like Multiple Sclerosis and Alzheimer’s Disease by delivering innovative, brain-penetrant nanobody therapeutics that provide precise and effective neuroprotection.