Trientine Hydrochloride

Polyamines — small, positively charged metabolites long studied for roles in cell growth and translation — directly chelate labile intracellular iron and thereby suppress ferroptosis, the iron-dependent form of regulated cell death, according to a study published August 14 in Cell. The finding repositions a class of abundant endogenous molecules as constitutive guardians of cellular redox homeostasis, with potential implications for cancer therapy and neurodegeneration research. The work was led by Whitehead Institute and MIT researchers Pushkal Sharma, Whitney Henry, and Ankur Jain, with contributors from Koch Institute, Institut Curie, Broad Institute, and MIT's Department of Biology. The work identifies a non-enzymatic protective mechanism operating in parallel to the well-characterized glutathione peroxidase 4 (GPX4) pathway. Prior models of ferroptosis resistance have centered on enzymatic lipid repair; this study proposes that polyamines — principally spermine and spermidine — provide a chemical buffering layer by sequestering the labile iron pool (LIP), the redox-active Fe²⁺ fraction that drives Fenton chemistry and lipid peroxide generation. The researchers conducted a genome-wide CRISPR knockout screen to identify synthetic lethal interactions with GPX4 loss. Polyamine depletion emerged as a top hit: cells lacking polyamine biosynthetic capacity were dramatically sensitized to ferroptosis when GPX4 was also inhibited. To investigate the mechanism, the team developed a genetically encoded fluorescent reporter for redox-active iron, enabling real-time, single-cell visualization of the LIP — a technical advance the paper presents as a significant methodological contribution alongside the biological findings. Live-cell imaging with this reporter revealed a striking inverse correlation between intracellular polyamine levels and labile Fe²⁺ at single-cell resolution. Biochemical assays confirmed that spermine and spermidine directly coordinate Fe²⁺ through their multiple protonatable amine nitrogen atoms, forming stable chelate complexes analogous in principle to clinical iron chelators such as trientine. When polyamines were depleted, the LIP expanded; cells partially compensated by upregulating ferritin, the iron storage protein, but the paper reports this secondary response was insufficient to fully buffer the excess reactive iron. The study draws a direct line from polyamine abundance to ferroptosis susceptibility: high polyamine levels sequester Fe²⁺, reducing its availability to catalyze lipid peroxidation; depletion expands the LIP and, in the absence of GPX4 activity, produces synthetic lethality. The authors note this framework provides a mechanistic rationale for the ferroptosis-sensitizing effects of difluoromethylornithine (DFMO, eflornithine), an ornithine decarboxylase inhibitor already FDA-approved for neuroblastoma, suggesting that its clinical activity may partly reflect iron dyshomeostasis rather than effects on proliferation alone. The connection also extends to genetic diseases involving polyamine dysregulation. The connection also extends to genetic diseases involving polyamine dysregulation. The paper cites ATP13A2 mutations linked to early-onset Parkinson's disease, as well as Snyder-Robinson syndrome, as examples of conditions in which disrupted polyamine homeostasis may intersect with disease Ferroptosis has attracted substantial drug development interest across oncology, neurodegeneration, and ischemia-reperfusion injury. GPX4 inhibitors and system Xc⁻ (cystine-glutamate antiporter) blockers are the principal pharmacological tools used to induce ferroptosis in cancer models, while the same pathway is a therapeutic target for protection in degenerative disease. The polyamine-iron axis identified here represents a distinct, non-enzymatic entry point into ferroptosis regulation that has not previously been described at this mechanistic level, according to the paper. The work is entirely preclinical with experiments conducted primarily in mammalian cell lines and organoid models. The genetically encoded iron reporter developed for this study may itself be a broadly useful research tool, but its performance characteristics across diverse cell types and conditions are not detailed in the available data. Whether polyamine-iron buffering operates equivalently across the cell types most relevant to cancer or neurodegeneration, and whether it can be pharmacologically exploited with sufficient selectivity, remain open questions. No therapeutic candidate or clinical development program is described. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article

Strategic partnership with Kyuan Xinhai (Beijing) Medical Products Trade Co., Ltd ("SPH Kyuan Trade") to transform access to Wilson's disease treatment for Chinese patients PARIS, March 7, 2025 /PRNewswire/ -- Orphalan, a global pioneer in orphan drug development and commercialization, achieves a historic milestone by launching its Wilson's disease treatment, " Ke Pei Ou" ( 科佩欧 ®), in China. This landmark achievement makes Orphalan the first European pharmaceutical company to introduce an orphan drug to the Chinese Wilson Disease market marking a significant step forward in global rare disease care. This launch is made possible through a strategic partnership with SPH Kyuan Trade, a leading pharmaceutical distributor in China and a subsidiary of Shanghai Pharma Group, one of the country's largest healthcare conglomerates. Together, Orphalan and SPH Kyuan Trade will work to dramatically expand patient access to this critical treatment. A New era for Wilson's disease patients in China Wilson's disease is a rare, life-threatening genetic disorder that affects the body's ability to eliminate excess copper. Without proper treatment, it can lead to severe neurological and hepatic complications. While penicillamine has been a standard therapy for years, many patients cannot tolerate it, leaving them with limited therapeutic options—until now. Orphalan's trientine tetrahydrochloride, "Ke Pei Ou" (科佩欧®), is the first trientine-based treatment approved by the NMPA (National Medical Products Administration) in China. Already available in more than 20 countries under the names Cuprior® (EU, UK, Saudi Arabia, Switzerland, Colombia, New Zealand) and Cuvrior® (US), this treatment should become a life changing therapy for thousands of patients in China. Now, under the name " Ke Pei Ou" ( 科佩欧 ®), it is commercially available in China, bringing new hope to thousands of patients who previously had no alternative. Orphalan expands its presence in China to ensure success Recognizing the strategic importance of China in its global mission, Orphalan has established a local entity in Shanghai and appointed Ms. Grace Li as General Manager. Backed by a team of scientific and medical experts, she will oversee efforts to: Engage with leading healthcare professionals to ensure they have access to the latest clinical data on Wilson's disease management. Facilitate knowledge-sharing and medical education, ensuring informed decision-making for both physicians and patients. Strengthen Orphalan's presence in the Chinese healthcare landscape, ensuring long-term success for "Ke Pei Ou" (科佩欧®). A defining moment for Orphalan's global expansion This milestone is part of Orphalan's broader commitment to advancing rare disease treatments worldwide. By successfully entering the highly regulated and competitive Chinese pharmaceutical market, the company is solidifying its role as a leader in orphan drug innovation and global patient access. Dr. Naseem Amin, CEO of Orphalan, underlined the significance of this achievement: "This is more than a market expansion—this is a breakthrough for rare disease patients in China. Our collaboration with SPH Kyuan Trade represents a pivotal moment in Orphalan's journey. We are not just bringing a treatment to market; we are revolutionizing access to care for those who need it most. This launch reaffirms our commitment to delivering life-changing therapies globally." As Orphalan continues to push the boundaries of scientific excellence and therapeutic innovation, it remains fully committed to ensuring that patients and healthcare providers in China have access to the latest advancements in Wilson's disease treatment. With Ke Pei Ou" ( 科佩欧 ®) now available in China, Orphalan is setting a new standard for what is possible in orphan drug development and global accessibility. About Orphalan Orphalan is an international orphan drug focused pharmaceutical company headquartered in Paris. Founded in 2011, the Company's purpose is to develop and deliver innovative therapies for people living with rare and debilitating diseases. Our commitment is to work collaboratively with the rare disease and scientific communities to develop evidence-based treatments in areas of unmet need. Our trientine tetrahydrochloride product has been approved for the treatment of Wilson disease and is available in more than 20 countries, branded as Cuprior® in EU, the UK, Saudi Arabia, Switzerland, Columbia and New Zealand, as Cuvrior® in the United States, and as Ke Pei Ou" in China. For more information visit and follow us on Linkedin: Orphalan. For more information, please contact: Orphalan Géraldine van den Broek, Head of Corporate & BD Tel: +33 (0)1 42 49 82 64 [email protected] Bien Commun Advisory Marie-Charlotte Potet 06 70 91 25 23 [email protected] Logo - SOURCE Orphalan WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED