Tiratricol 350microgram tablets

Yellow fever virus (YFV) infection is a major public concern that threatens a large population in South America and Africa. No specific antiviral drugs are available for treating yellow fever. Here, we report that tiratricol (triiodothyroacetic acid, TRIAC), a clinically approved drug used to treat thyroid hormone resistance syndrome (THRS), is a potent YFV inhibitor both in host cells and in animal models.An in vitro study demonstrates that TRIAC remarkably suppresses viral RNA synthesis and protein expression in a dose-dependent manner in human hepatoma cell lines (Huh-7) with an EC50 value of 2.07 μM and a CC50 value of 385.77 μM respectively. The surface plasmon resonance assay and molecular docking analysis indicate that TRIAC hinders viral replication by binding to the RNA-dependent RNA polymerase (RdRp) domain of viral nonstructural protein NS5, probably through interacting with the active sites of RdRp.The inhibitory effect of TRIAC in vivo is also confirmed in 3-week old C57BL/6 mice challenged with YFV infection, from which the survival of the mice as well as lesions and infection in their tissues and serum issignificantly promoted following oral administration of TRIAC (0.2 mg/kg/day). Additionally, TRIAC shows a broad-spectrum antiviral activity against multiple flaviviruses such as TBEV, WNV,ZIKV, andJEV in vitro. Our data demonstrate that the TH analogue TRIAC is an effective anti-YFV compound and may act as a potential therapeutic candidate for the treatment of YFV infection if its clinical importance is determined in patients in future.

Abstract licence: CC BY-NC

Monocarboxylate transporter 8 (MCT8) deficiency, also known as Allan–Herndon–Dudley syndrome, is a rare genetic disorder affecting thyroid hormone transport. It is characterised by severely debilitating neurodevelopmental and endocrinological impairments, further complicated by numerous diagnostic challenges. Here, we describe the clinical journey of a male infant from birth to MCT8 deficiency diagnosis at 23 months of age and 20 months of follow-up post diagnosis. The patient presented with hypotonia, abnormal thyroid hormone levels, epilepsy and failure to gain weight. A diagnosis of MCT8 deficiency was confirmed upon identifying a pathogenic variant in the SLC16A2 gene, which encodes the MCT8 protein. The patient was initiated on 350 μg daily of tiratricol, escalated to 350 μg twice daily, and following intolerance during further escalation, the dose was maintained at 350 μg twice daily. With 11 months of treatment follow-up, the patient has shown promising signs of thyroid hormone normalization and improved weight gain. This case highlights the importance of early recognition and a well-coordinated multidisciplinary team spanning numerous specialisms to optimise outcomes for patients with MCT8 deficiency, while providing real-world data on the effects of tiratricol treatment. • At three months of age, a male patient rapidly developed hypotonia. • He exhibited abnormal thyroid levels, poor weight gain and abnormal neurodevelopmental findings. • MCT8 deficiency was diagnosed upon the discovery of a pathogenic SLC16A2 variant. • Tiratricol treatment enabled weight gain and partial thyroid hormone normalization.

Abstract licence: CC BY-NC-ND

Tiratricol, an old thyroid drug, has been repurposed as an orphan drug for Allan-Herndon-Dudley syndrome, a rare genetic disorder affecting thyroid hormone transport. Despite public contributions to its repurposing, the current marketing authorization holder, Egetis Therapeutics, has projected a price of €63.500–€95.000 per-patient-per year, significantly exceeding historical costs and straining already limited healthcare budgets. This raises concerns regarding affordability and the justification for charging high prices for medicines repurposed with public funding. This study evaluates a cost-based-plus pricing approach for repurposed tiratricol across different scenarios with varying cost structures and different assumptions about patient numbers. By transparently outlining key cost components, including R&D costs, cost-of-failure, and cost-of-capital, it proposes socially acceptable pricing that reflects genuine investment needs and a reasonable profit margin. Under the maximum cost scenario, assuming fewer patients than projected by the company itself, a price of €27.600 per-patient-per-year is derived. Minimum cost scenarios and those projecting a higher number of patients yield prices ranging from €5.300 to €16.500. Given the substantial public role in tiratricol’s repurposing, this study argues in favour of the lower end of the price range, while acknowledging the need for sustainable access through formal registration, which justifies a price higher than that of the original product. This research highlights the broader ethical and economic implications of orphan drug pricing, advocating for evidence-based policies that promote transparency in cost structures. This can help ensure a more predictable, sustainable, and socially responsible business model for repurposed medicines.

Abstract licence: CC BY