– The oral presentation at AAO 2022 suggests that IGF-1 and its related pathways are broadly regulated at all stages of TED.
DUBLIN–( BUSINESS WIRE )–Horizon Therapeutics plc (Nasdaq: HZNP) today announced the presentation of new data that define molecular patterns in TED and further implicate the role of insulin-like growth factor-1 (IGF -1) in patients with low CAS. These data were presented during the annual meeting of the American Academy of Ophthalmology (AAO 2022), from September 30 to October 3 in Chicago.
TED is a rare progressive and potentially vision-threatening autoimmune disease that has historically been characterized as biphasic: acute, traditionally thought to be patients with elevated CAS and prior to their TED journey; and chronic, traditionally thought to be patients with low CAS and later in the course of their disease.1 This analysis reveals that in patients with both high and low CAS, there is a clear activation of IGF-1 and the related pathways, as well as the organization of the extracellular matrix (ECM), a structural network that supports cellular processes.2
“By showing that disease activity remains in patients with low CAS, this analysis may help explain why many patients who have lived with thyroid eye disease for several years are still struggling with difficult symptoms that can be debilitating,” said Shoaib Ugradar, MD, The Jules Stein Eye Institute at the University of California, Los Angeles (UCLA). “It is important for clinicians to be aware of the continued activation of IGF-1 throughout the course of the disease and its potential impact on treatment decisions.”
The study analyzed the ribonucleic acid (RNA) genome sequencing and analysis of pathways in orbital tissue from patients with a CAS ≥ 3 and patients with a CAS ≤ 2, as well as five control subjects. Although patients with high CAS are often distinguished by the activation of immune system pathways, which remain largely unaffected in patients with low CAS, IGF-1 and its related pathways were found to be regulated in both stages of the disease. Further analysis suggests that IGF-1 activity plays a central role in linking the immune and ECM pathways in people with TED.2
The upregulation of IGF-1 found in low CAS patients with prolonged disease duration is further supported by a growing body of evidence describing the impact of TED in individuals who have lived with him for several years.3 An evaluation published in the magazine. Ophthalmology and Therapy in 2021 found that disease burden continues well into the chronic phase, affecting daily life with persistent visual appearance and changes, increasing the risk of anxiety and depression.4
“This study, which represents one of the first molecular analyzes of the thyroid eye disease continuum, confirms that this challenging disease may not go away after years of obvious symptoms,” said Jeffrey W. Sherman, MD, FACP, Executive Vice President. , Medical Director, Horizon. “We are committed to pioneering research like this to better understand the drivers of this disease’s evolution in order to better support patients with thyroid eye disease throughout their lives.”
About Thyroid Eye Disease (TED)
TED is a serious, progressive, and potentially vision-threatening rare autoimmune disease. 1 TED often occurs in people living with Graves’ disease, but it is a distinct disease that is caused by autoantibodies that activate a signaling complex mediated by IGF-1R in the cells of the retroorbital space.5,6 This leads to a cascade of negative effects, which can cause long-term and irreversible damage, including blindness. Early signs and symptoms of TED may include dry, gritty eyes; redness, swelling and excessive tearing; retraction of the eyelids; proptosis; pressure and/or pain behind the eyes; and diplopia.7,8
About Horizon
Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address the critical needs of people affected by rare, autoimmune and severe inflammatory diseases. Our pipeline has a purpose: we apply scientific knowledge and courage to deliver clinically meaningful therapies to patients. We believe that science and compassion must work together to transform lives. To learn more about how we do incredible work to impact lives, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.
References
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Barrio-Barrio J, et al. Graves’ ophthalmopathy: VISA versus EUGOGO classification, assessment and management. Journal of Ophthalmology. 2015;2015:249125.
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Ugradar S, et al. Genome-wide transcriptome comparison of acute and chronic thyroid eye disease: emergence of a molecular signature. Oral presentation at: American Academy of Ophthalmology (AAO); September 30, 2022 – October 1; Chicago, IL.
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Wang Y et al. Inflammatory and noninflammatory thyroid eye disease: comparison of disease signs, symptoms, and quality of life in US patients. Endo practice. 2022;28(9):842-846.
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Cockerham KP, et al. Quality of life in patients with chronic thyroid eye disease in the United States. Ophthalmol Ther. 2021;10(4):975-987.
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Weightman DR, et al. Autoantibodies to IGF-1 binding sites in thyroid-associated ophthalmopathy. Autoimmunity. 1993;16(4):251–257.
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Pritchard J, et al. Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves’ disease is mediated through the insulin-like growth factor receptor 1 pathway. J Immunol. 2003;170:6348-6354.
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Bartalena L, Kahaly GJ, Baldeschi L, et al. European Graves’ Orbitopathy Group 2021 (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185:G43-G67.
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McKeagh D, et al. Clinical features of dysthyroid optic neuropathy: a European Graves’ Orbitopathy Group (EUGOGO) survey. Br J Ophthalmol. 2007;91:455-458.
contacts
Investors:Tina VenturaSenior Vice President, Director of Investor Relations Investor-relations@horizontherapeutics.com
US media:Rachel VannSenior Director, Product Communications media@horizontherapeutics.com
Irish media:Gordon MRM
Ray Gordon ray@gordonmrm.ie