— Oral presentation at AAO 2022 suggests IGF-1 and its related pathways are extensively upregulated throughout all stages of TED —
DUBLIN–(BUSINESS WIRE)–Horizon Therapeutics plc (Nasdaq: HZNP) today announced the presentation of new data defining molecular patterns in TED and further implicating the role of insulin-like growth factor-1 (IGF-1) in patients with low CAS. These data were presented during the American Academy of Ophthalmology Annual Meeting (AAO 2022), Sept. 30 – Oct. 3 in Chicago.
TED is a progressive and potentially vision-threatening rare autoimmune disease, which has been historically characterized as biphasic: acute, which is traditionally believed to be patients with high CAS and earlier in their TED journey; and chronic, traditionally believed 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 clear activation of IGF-1 and related pathways, as well as the extracellular matrix (ECM) organization, a structural network that supports cellular processes.2
“By demonstrating 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 challenging symptoms that can be debilitating,” said Shoaib Ugradar, M.D., The Jules Stein Eye Institute at University of California, Los Angeles (UCLA). “It is important for physicians 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 genome ribonucleic acid (RNA)sequencing and pathway analysis in orbital tissue from patients with a CAS of ≥ 3 and patients with a CAS ≤ 2, as well as five control subjects. Though high CAS patients are often distinguished by activation of immune system pathways, which remain largely unaffected in low CAS patients, IGF-1 and its related pathways were found to be upregulated in both stages of disease. Additional analysis suggests that IGF-1 activity plays a central role in linking immune and ECM pathways in people with TED.2
The upregulation of IGF-1 found in low CAS patients with extended disease duration is further supported by a growing body of evidence that outlines the impact of TED on people who have lived with it for several years.3 One assessment published in the journal Ophthalmology and Therapy in 2021 found that disease burden continues well into the chronic phase, affecting daily lives with appearance and persistent visual changes, increasing risk for anxiety and depression.4
“This study, which represents one of the first molecular analyses of the continuum of Thyroid Eye Disease, confirms this challenging disease may not simply subside after a few years of obvious symptoms,” said Jeffrey W. Sherman, M.D., FACP, executive vice president, chief medical officer, Horizon. “We are committed to pioneering research like this to better understand drivers of the evolution of this disease in order to better support patients living with Thyroid Eye Disease across the course of their lifetimes.”
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 is a distinct disease that is caused by autoantibodies activating an IGF-1R-mediated signaling complex on cells within the retro-orbital space.5,6 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness. Early signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; 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 critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.
References
Barrio-Barrio J, et al. Graves’ Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:249125.
Ugradar S, et al. Whole Genome Transcriptome Comparison of Acute and Chronic Thyroid Eye Disease: Emergence of a Molecular Signature. Oral presentation at: American Academy of Ophthalmology (AAO); 2022 Sept. 30- Oct. 1; Chicago, IL.
Wang Y, et al. Inflammatory and non-inflammatory thyroid eye disease: comparison of disease signs, symptoms and quality of life in US patients. Endo Practice. 2022;28(9):842-846.
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.
Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257.
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 1 Receptor Pathway. J Immunol. 2003;170:6348-6354.
Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves’ Orbitopathy. Eur J Endocrinol. 2021;185:G43-G67.
McKeag D, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves’ Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007;91:455-458.
Contacts
Investors: Tina Ventura Senior Vice President, Chief Investor Relations Officer
VANCOUVER – Mayors and other leaders from several British Columbia communities say the provincial and federal governments need to take “immediate action” to tackle mental health and public safety issues that have reached crisis levels.
Vancouver Mayor Ken Sim says it’s become “abundantly clear” that mental health and addiction issues and public safety have caused crises that are “gripping” Vancouver, and he and other politicians, First Nations leaders and law enforcement officials are pleading for federal and provincial help.
In a letter to Prime Minister Justin Trudeau and Premier David Eby, mayors say there are “three critical fronts” that require action including “mandatory care” for people with severe mental health and addiction issues.
The letter says senior governments also need to bring in “meaningful bail reform” for repeat offenders, and the federal government must improve policing at Metro Vancouver ports to stop illicit drugs from coming in and stolen vehicles from being exported.
Sim says the “current system” has failed British Columbians, and the number of people dealing with severe mental health and addiction issues due to lack of proper care has “reached a critical point.”
Vancouver Police Chief Adam Palmer says repeat violent offenders are too often released on bail due to a “revolving door of justice,” and a new approach is needed to deal with mentally ill people who “pose a serious and immediate danger to themselves and others.”
This report by The Canadian Press was first published Sept. 16, 2024
The Canadian government says it will donate up to 200,000 vaccine doses to fight the mpox outbreak in Congo and other African countries.
It says the donated doses of Imvamune will come from Canada’s existing supply and will not affect the country’s preparedness for mpox cases in this country.
Minister of Health Mark Holland says the donation “will help to protect those in the most affected regions of Africa and will help prevent further spread of the virus.”
Dr. Madhukar Pai, Canada research chair in epidemiology and global health, says although the donation is welcome, it is a very small portion of the estimated 10 million vaccine doses needed to control the outbreak.
Vaccine donations from wealthier countries have only recently started arriving in Africa, almost a month after the World Health Organization declared the mpox outbreak a public health emergency of international concern.
A few days after the declaration in August, Global Affairs Canada announced a contribution of $1 million for mpox surveillance, diagnostic tools, research and community awareness in Africa.
On Thursday, the Africa Centres for Disease Control and Prevention said mpox is still on the rise and that testing rates are “insufficient” across the continent.
Jason Kindrachuk, Canada research chair in emerging viruses at the University of Manitoba, said donating vaccines, in addition to supporting surveillance and diagnostic tests, is “massively important.”
But Kindrachuk, who has worked on the ground in Congo during the epidemic, also said that the international response to the mpox outbreak is “better late than never (but) better never late.”
“It would have been fantastic for us globally to not be in this position by having provided doses a much, much longer time prior than when we are,” he said, noting that the outbreak of clade I mpox in Congo started in early 2023.
Clade II mpox, endemic in regions of West Africa, came to the world’s attention even earlier — in 2022 — as that strain of virus spread to other countries, including Canada.
Two doses are recommended for mpox vaccination, so the donation may only benefit 100,000 people, Pai said.
Pai questioned whether Canada is contributing enough, as the federal government hasn’t said what percentage of its mpox vaccine stockpile it is donating.
“Small donations are simply not going to help end this crisis. We need to show greater solidarity and support,” he said in an email.
“That is the biggest lesson from the COVID-19 pandemic — our collective safety is tied with that of other nations.”
This report by The Canadian Press was first published Sept. 13, 2024.
Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.
HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.
The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.
Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.
“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”
The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.
A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.
Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.
“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.
Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.
The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.
“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.
This report by The Canadian Press was first published Sept. 11, 2024.
