Io Therapeutics, Inc. has announced the presentation of data from studies evaluating IRX4204, a Phase II clinical-stage RXR agonist, for its potential in preventing and treating neurodegeneration related to normal aging. The findings were shared at the FASEB Science Research Conference on Cellular and Molecular Mechanisms of Brain Aging in Niagara Falls, NY.
Addressing Neuro-Inflammaging
Normal aging-related neurodegeneration is closely linked to chronic low-grade inflammation in the brain, a condition known as neuro-inflammaging. This process leads to the gradual loss of myelinated nerve fibers, disrupting neuroelectric signal transmission, and eventually causing neuronal death. These changes typically begin around the third decade of life, progressively impacting cognitive, memory, sensory, and physical functions.
IRX4204's Mechanisms of Action
Studies have demonstrated that IRX4204 effectively inhibits brain inflammation by reducing the production of the pro-inflammatory cytokine IL-6 by microglial cells. Furthermore, it stimulates the growth of immunosuppressive regulatory Treg cells and inhibits the production of the pro-inflammatory cytokine IL-17 by Th17 cells. These mechanisms target key aspects of neuroinflammation observed in normal aging-related neurodegeneration.
IRX4204 also promotes the development of myelin-producing cells, which are crucial for protecting and repairing damaged myelinated nerve fibers. Additionally, the compound has direct neuroprotective and neurorestorative effects, enhancing neuron survival and promoting neurite growth. These effects were observed both with IRX4204 alone and synergistically in combination with insulin, indicating that IRX4204 has insulin-sensitizing activity on neurons. Neuronal insulin insensitivity is a known factor contributing to brain aging.
Potential for Reversing Cognitive Decline
"These findings support the potential of IRX4204 for prevention and treatment of normal aging-related neurodegeneration," said Dr. Vidyasagar Vuligonda, Chief Science Officer at Io Therapeutics. "Because we observed restoration of lost myelinated nerve fibers, and formation of new neurites, both of which could restore functional inter-neuronal communications, we believe that IRX4204 has potential for reversing to some degree the cognitive decline and other disabling manifestations of normal brain aging."
Clinical Trial Plans
Io Therapeutics is planning a placebo-controlled, double-blind Phase II clinical trial of IRX4204 in Parkinson’s disease, scheduled to begin in Q1 2025. The company is also considering exploratory clinical trials of IRX4204 in individuals experiencing normal-aging related neurodegeneration, according to Dr. Martin E. Sanders, Chief Executive Officer.
