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SPRING, Texas, July 9, 2024 (GLOBE NEWSWIRE) — IO Therapeutics today presented results from studies on the potential prevention and treatment of neurodegeneration associated with normal aging, Parkinson’s disease and Alzheimer’s disease, using its clinical-stage investigational therapeutic compound IRX4204, a nuclear RXR receptor antagonist. IRX4204 is a highly potent, highly selective, orally available, brain-active third-generation RXR receptor antagonist that has been tested in early clinical trials in patients with Parkinson’s disease or cancer. The presentation, “Potent and Selective RXR Receptor IRX4204 Is a Potential Treatment for Neurodegeneration Associated with Normal Aging, Parkinson’s Disease (PD) and Alzheimer’s Disease (AD),” was presented at the 7th FASEB International Conference on Retinoids, held in St. Paul, Minnesota, USA. The presentation was authored by Dr. Vidyasagar Phulegunda, the company’s chief science officer and inventor of IRX4204, and Dr. Martin E. Sanders, the company’s CEO.
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Neurodegeneration associated with normal aging has been reported to be strongly associated with chronic, low-grade inflammation in the brain, called neuroinflammation. Neuroinflammation results in chronic loss of myelinated nerve fibers, disrupting functional electrical communication between neurons in different parts of the brain. Chronic neuroinflammation ultimately leads to neuronal death. These neurodegenerative processes lead to memory loss, cognitive impairment, and other functional impairments in patients with normal brain aging, and in various types of neurological conditions including Parkinson’s and Alzheimer’s disease.
Neuroinflammation is associated with an imbalance between immunosuppressive regulatory T cells (Treg) and increased production of the pro-inflammatory cytokine interleukin-17 (IL-17) by T cells (Th17) in the brain. Neuroinflammation is also associated with overactivity of microglia in the brain, which produce the pro-inflammatory cytokine interleukin-6 (IL-6) and other pro-inflammatory factors.
The brains of patients with Parkinson’s and Alzheimer’s disease show neuroinflammatory pathologies similar to those observed in normal brain aging, but also have distinct pathologies related to the deposition of abnormal misfolded proteins such as alpha-synuclein in Parkinson’s disease and beta-amyloid in Alzheimer’s disease. It is generally accepted within the neurodegenerative disease research community that neuroinflammation creates a compromised environment within the brain, which may increase susceptibility to Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative diseases.
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The presented studies showed that IRX4204 promotes the differentiation and growth of human immunosuppressive regulatory T cells, and inhibits the differentiation of human pro-inflammatory Th17 cells, while reducing the production of IL-17. IRX4204 also inhibits the production of IL-6 and other pro-inflammatory factors by microglia. In addition, IRX4204 promotes the differentiation and growth of myelin-producing oligodendrocytes. in the laboratory It promotes the protection and repair of myelinated nerve fibers (remyelination) in mouse models of demyelination. IRX4204 has shown direct beneficial effects alone, and additionally in combination with insulin or thyroid hormone on cortical neurons. in the laboratoryThese findings promote neurite outgrowth, a neural repair mechanism by which damaged neurons can re-establish functional connections with other neurons. These findings support the possibility that IRX4204 may protect against or even reverse chronic myelin loss caused by neuroinflammation and neuronal damage in normal brain aging and neurodegenerative diseases.
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Further clarification of the beneficial effects of IRX4204 in neurodegeneration was provided by Alive Studies have been conducted in rodent models of Parkinson’s disease and Alzheimer’s disease. IRX4204 effectively reduced motor deficits in a mouse model of Parkinson’s disease while increasing the survival of dopaminergic neurons in the brains of mice. In a genetically modified mouse model of Alzheimer’s disease, IRX4204 reduced the deposition of new beta-amyloid in the brains of mice while preserving memory function in the mice.
IRX4204 has demonstrated safety and tolerability at oral doses in Phase I/II clinical trials in 85 patients with various cancers and 15 patients with Parkinson’s disease for up to 20 months of continuous treatment. In Parkinson’s patients, IRX4204 demonstrated brain penetration and motor function improvements in 13 of 15 patients in open-label assessments. The Company plans to initiate a Phase II placebo-controlled clinical trial of IRX4204 in Parkinson’s patients in Q4 2024, to further demonstrate safety and efficacy in Parkinson’s patients.
“Our findings identify a new approach to slow or reverse the neurodegeneration that accompanies normal aging, as well as to treat the pathological conditions of Parkinson’s disease and Alzheimer’s disease, which cause severe chronic decline in cognitive and other functional abilities,” said Dr. Volegonda.
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“IRX4204 has been shown to be safe and well-tolerated in patients and has the potential to be an effective single agent for the prevention or treatment of the debilitating neurological manifestations associated with normal aging, Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative conditions,” said Dr. Sanders. “In addition, IRX4204 provides opportunities for the development of future combination therapies that are more effective for these conditions, by administering IRX4204 with other well-tolerated and already available agents, such as insulin, GLP-1 agonists, other neurotrophic factors, thyroid hormone, or anti-beta-amyloid monoclonal antibodies. We believe that multi-agent combination therapies including IRX4204 will enable the development of well-tolerated and highly effective preventive and therapeutic interventions for a variety of neurodegenerative diseases.”
About Io Therapeutics: Io Therapeutics, Inc. is a privately held company headquartered in Spring, Texas. More information about Io Therapeutics and its product development programs is available on the company’s website: www.io-therapeutics.com
Forward-Looking Statements: This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995.
communication:
info@io-therapeutics.com
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