New data reveals that molecular drivers of TED may remain activated in patients with a low clinical activity score

New data reveals that molecular drivers of TED may remain activated in patients with a low clinical activity score

Horizon Therapeutics plc recently announced the submission of new data

define molecular patterns in thyroid eye disease (TED) and further implicate the role of insulin-like growth factor-1 (IGF-1) in patients with low clinical activity score (CAS).

These data were presented at the 2022 annual meeting of the American Academy of Ophthalmology, held recently in Chicago.

According to a company press release, TED is a rare progressive and potentially vision-threatening autoimmune disease that has historically been characterized as biphasic: acute, traditionally believed to be patients with high CAS and earlier in their TED journey. ; and chronic, which are traditionally believed to be patients with low BAC and later in the course of their disease.1This analysis reveals that in patients with high and low BAC, there is a clear activation of IGF-1 and related pathways, as well as the organization of the extracellular matrix (ECM), a structural network that supports cellular processes.two

“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 still struggle with challenging symptoms that can be debilitating,” Shoaib said. Ugradar, MD, The Jules Stein Eye Institute at the University of California, Los Angeles (UCLA), said in the statement. “It is important for clinicians to be aware of the ongoing activation of IGF-1 throughout the course of the disease and its potential impact on treatment decisions.”

According to the press release, the study looked at genome ribonucleic acid (RNA) sequencing and pathway analysis in orbital tissue from patients with a CAS of ≥ 3 and patients with a CAS of ≤ 2, as well as five control subjects. Although high BAC patients are often distinguished by activation of immune system pathways, which are largely unaffected in low BAC patients, IGF-1 and its related pathways were found to be upregulated 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.two

The IGF-1 upregulation found in low BAC patients with prolonged disease duration is supported by a growing body of evidence describing the impact of TED in people who have lived with it for several years.3An evaluation published in the journalOphthalmology and Therapyin 2021 found that the burden of the disease continues well into the chronic phase, affecting daily life with persistent visual and appearance changes, increasing the risk of anxiety and depression.4

“Representing one of the first molecular analyzes of the thyroid eye disease continuum, this study confirms that this challenging disease may not simply go away after a few years of overt symptoms,” said Jeffrey W. Sherman, MD, FACP, Executive Vice President, Medical Director of Horizon. “We are committed to pioneering research like this to better understand the drivers of this disease progression in order to better support patients living with thyroid eye disease throughout their lives.”

References

  1. Barrio-Barrio J, et al. Graves’ ophthalmopathy: VISA versus EUGOGO classification, evaluation, and management. Journal of Ophthalmopathy. 2015;2015:249125.
  2. 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); 2022 September 30 – October 1; Chicago, Ill.
  3. WangY, et al. Inflammatory and noninflammatory thyroid eye disease: comparison of disease signs, symptoms, and quality of life in American patients. endodontic practice. 2022;28(9):842-846.
  4. 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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