Mechanisms of Action
Our investigational therapy targets key biochemical pathways that are disrupted in MCT-8 deficiency, with a focus on thyroid hormone transport, neurotransmitter balance, and cellular energy production. By modulating specific pathways, including 3-OMD and 5-HTP, we aim to address the underlying neurochemical imbalances that contribute to developmental and neurological symptoms in MCT-8 deficiency.
Thyroid Hormone Transport & Activation
Pathway Disruption:
MCT-8 mutations impair cellular uptake of triiodothyronine (T3), resulting in elevated serum T3 levels and insufficient thyroid hormone action in the brain. This disrupts key neurodevelopmental processes and thyroid signaling.
Therapeutic Mechanism:
​
Our therapy enhances alternative thyroid hormone transport pathways and stabilizes systemic T3 levels to restore intracellular thyroid signaling. These mechanisms are designed to support proper thyroid hormone function across neurological and systemic tissues.
Homocysteine-Methionine Pathway and Methylation Support
​
Pathway Disruption:
Elevated homocysteine impairs methylation reactions critical for DNA repair, myelination, and neurotransmitter synthesis. Methylation imbalances may contribute to the neurological and metabolic symptoms seen in MCT-8 deficiency.
Therapeutic Mechanism:
Our therapy is expected to promote homocysteine clearance and support methylation balance by:
​
-
Increasing S-adenosylmethionine (SAM) availability, ensuring sufficient methyl donor supply for neurotransmitter production.
​
-
Enhancing remethylation of homocysteine to methionine.
Dopamine and Serotonin Pathways
Modulating 3-OMD and 5-HTP Metabolism to Promote Neurogenesis and Neuroplasticity
​
Pathway Disruption:
Dopamine (3-OMD Pathway): In MCT-8 deficiency, thyroid hormone imbalances disrupt dopamine synthesis and metabolism, leading to elevated 3-O-Methyldopa (3-OMD) levels, which can hinder dopamine receptor function. High 3-OMD levels may also contribute to neurotoxicity, further impairing neurodevelopment and cognitive function.
​
Serotonin (5-HTP Pathway): Reduced thyroid hormone signaling limits the availability of 5-Hydroxytryptophan (5-HTP), the precursor to serotonin, which in turn decreases serotonin synthesis. Low serotonin levels are associated with mood dysregulation, anxiety, and cognitive impairments, contributing to developmental and neurological deficits.
Therapeutic Mechanism: Our therapy targets these pathways through mechanisms that promote neurogenesis, neuroplasticity, and decreased neurotoxicity:
-
Reducing 3-OMD Accumulation: By normalizing thyroid hormone signaling in the brain, our therapy is expected to regulate dopamine production and reduce the accumulation of 3-OMD. This is expected to help restore dopamine receptor activity and enhances neurogenesis – particularly in brain regions responsible for learning and memory. Reducing 3-OMD is also expected to mitigate neurotoxicity, protecting neuronal integrity and supporting overall cognitive function.
​
-
Supporting 5-HTP Availability and Conversion: Through cofactor support and methylation, our therapy is expected to optimize the conversion of 5-HTP to serotonin. This not only would restore serotonin balance but also promote neuroplasticity, thus allowing for more flexible neural connections and improved cognitive and emotional regulation.
-
Enhancing Neurogenesis and Neuroplasticity: The restoration of balanced dopamine and serotonin pathways fosters an environment conducive to neurogenesis – particularly in regions like the hippocampus, which is involved in memory and learning. Neuroplasticity is also expected to be enhanced, to support the brain’s ability to adapt to new learning and recover from neurodevelopmental deficits.
​
-
Decreasing Neurotoxicity: By improving oxidative stress response and restoring proper neurotransmitter balance, our product is expected to reduce the neurotoxic effects commonly seen in MCT-8 deficiency. This effected is expected to help protect neurons from damage, reduce the risk of long-term neurodegenerative effects and promote healthier brain function.
Oxidative Stress and Mitochondrial Dysfunction Pathway
​
Pathway Disruption:
​
Reduced mitochondrial efficiency and increased oxidative stress are common in MCT-8 deficiency, contributing to neurodegeneration and impaired neurotransmitter synthesis.
​
Therapeutic Mechanism:
Our therapy is expected to enhance mitochondrial function and antioxidant defenses by:
-
Supporting ATP production and cellular energy balance.
​​
-
Reducing reactive oxygen species (ROS) to protect dopamine and serotonin pathways from degradation.
Myelination and Brain Development Pathways
​
Pathway Disruption:
​
Thyroid hormones are essential for myelin synthesis and oligodendrocyte function. Insufficient thyroid hormone action in the brain impairs myelination, leading to delayed neural conduction and developmental challenges.
​
Therapeutic Mechanism:
​
Our therapy is expected to support myelin production through enhanced thyroid signaling and methylation-driven synthesis of key myelin components, promoting proper neural development and conduction.
