Article
Genetics & Heredity
Daniele De Brasi, Francesca Orlando, Valeria Gaeta, Maria De Liso, Fabio Acquaviva, Luigi Martemucci, Augusto Mastrominico, Maja Di Rocco
Summary: FOP is an ultra-rare genetic condition characterized by extraskeletal bone formation, with activating mutations of the ACVR1 gene being responsible for the skeletal and nonskeletal features. The clinical phenotype includes congenital bilateral hallux valgus malformation and early-onset heterotopic ossification, with essential care interventions focusing on avoiding unnecessary surgeries and administering medications to control inflammation.
Review
Biochemistry & Molecular Biology
Roberto Ravazzolo, Renata Bocciardi
Summary: This article summarizes the basic research on the genetic mutation responsible for FOP, including advancements in related fields and potential therapeutic approaches. It also explores the reasons why the single mutation R206H in the ACVR1 gene is highly prevalent in FOP patients, as well as factors that may modulate FOP expression.
Article
Pediatrics
Joshua Chun Ki Chan, Evelyn Eugenie Kuong, Joyce Pui Kwan Chan, Ho Ming Luk, Jasmine Lee Fong Fung, Joanna Yuet-ling Tung, Brian Hon Yin Chung
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare condition with challenging diagnosis due to its rarity and non-specific symptoms. Early diagnosis and suitable management are crucial for preserving patients' function and quality of life. This report shares the diagnostic journeys and clinical courses of 8 FOP patients in Hong Kong, highlighting the associated challenges.
FRONTIERS IN PEDIATRICS
(2023)
Article
Medicine, Research & Experimental
John B. Lees-Shepard, Sean J. Stoessel, Julian T. Chandler, Keith Bouchard, Patricia Bento, Lorraine N. Apuzzo, Parvathi M. Devarakonda, Jeffrey W. Hunter, David J. Goldhamer
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive and catastrophic heterotopic ossification (HO). This study found that a monoclonal blocking antibody, JAB0505, exacerbated injury-induced HO in FOP mouse models, raising concerns about its safety and efficacy for treating FOP patients.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Pediatrics
Ambika Gupta, Puneeta Mishra, Madhumita Roy Chowdhury, Shah Alam Khan, Manisha Jana, Madhulika Kabra, Neerja Gupta
Summary: This study evaluates the natural history of Fibrodysplasia Ossificans Progressiva (FOP) and highlights possible masqueraders causing diagnostic delay and iatrogenic interventions. The findings indicate that clinical suspicion followed by molecular testing is a straightforward and effective method for confirming FOP. Diagnostic delay may result in disease progression and unnecessary invasive interventions.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Cell Biology
Xinmiao Meng, Haotian Wang, Jijun Hao
Summary: FOP is a rare genetic disease caused by mutations in the ALK2 gene, leading to heterotopic ossification. Effective therapies are currently unavailable, but significant advances have been made in drug development.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Frederick S. Kaplan, David T. Teachey, Jeffrey R. Andolina, David M. Siegel, Edna E. Mancilla, Edward C. Hsiao, Mona Al Mukaddam, David M. Rocke, Robert J. Pignolo
Summary: This study reported improvements in symptoms in three children with FOP treated with imatinib, supporting the design of further clinical trials.
Review
Biochemistry & Molecular Biology
Fatima Khan, Xiaobing Yu, Edward C. Hsiao
Summary: Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare disorder characterized by heterotopic ossifications at extraskeletal sites. It is caused by gain-of-function mutations in the Acvr1/Alk2 gene, leading to severe cardiopulmonary and neurological dysfunctions.
Article
Endocrinology & Metabolism
Haitao Wang, Carmen L. De Cunto, Robert J. Pignolo, Frederick S. Kaplan
Summary: Progressive heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP) exhibits distinctive spatial and temporal patterns, correlating with infrared thermographs of the human body. Dysregulated temperature response of connective tissue progenitor cells in FOP patients influences the anatomical distribution of HO initiation and sustainment at various sites. This provides insights into potential therapeutic targets for this disabling condition.
Article
Developmental Biology
O. Will Towler, Sun H. Peck, Frederick S. Kaplan, Eileen M. Shore
Summary: The development of joints in mammals and the formation of skeletal structures are greatly influenced by the BMP pathway and mutations in the ACVR1 gene can lead to FOP, affecting both joint and skeletal development.
DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Francesc Ventura, Eleanor Williams, Makoto Ikeya, Alex N. Bullock, Peter ten Dijke, Marie-Jose Goumans, Gonzalo Sanchez-Duffhues
Summary: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare congenital disease caused by heterozygous gene point mutations in the ACVR1 gene, leading to ectopic bone formation. Although there is no approved cure for FOP yet, multiple clinical trials are underway to find safe and effective treatments for this condition.
Article
Biochemistry & Molecular Biology
Ruben D. D. de Ruiter, Lisanne E. E. Wisse, Ton Schoenmaker, Maqsood Yaqub, Gonzalo Sanchez-Duffhues, E. Marelise W. Eekhoff, Dimitra Micha
Summary: FOP is an ultra-rare disease caused by genetic defects in the ACVR1 gene. We found that FOP patients have elevated Activin A production in their fibroblasts, and TGF beta 1 is a specific stimulant of Activin A in FOP. This study is the first to identify TGF beta 1 as a triggering factor of Activin A production in FOP, suggesting it as a possible therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yeon-Suk Yang, Jung-Min Kim, Jun Xie, Sachin Chaugule, Chujiao Lin, Hong Ma, Edward Hsiao, Jaehyoung Hong, Hyonho Chun, Eileen M. Shore, Frederick S. Kaplan, Guangping Gao, Jae-Hyuck Shim
Summary: The study developed gene therapy approaches that demonstrated efficacy in mouse models and human induced pluripotent stem cells, showing potential for preventing disabling heterotopic ossification in fibrodysplasia ossificans progressiva. These promising treatments could offer significant clinical benefits for patients with this rare genetic disorder.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Serena Cappato, Rasa Traberg, Jolita Gintautiene, Federico Zara, Renata Bocciardi
Summary: Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disease characterized by congenital malformation of the great toes and progressive heterotopic ossification of soft tissues. A novel variant in the ACVR1 gene was identified in a 3-year-old child with early and highly suggestive clinical features of FOP, despite the absence of the recurrent p.R206H substitution commonly found in FOP patients.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Editorial Material
Rheumatology
Carlos Enrique Suarez Acosta, Esperanza Romero Fernandez
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by progressive disability due to extensive bone formation and malformed big toes. The disease immobilizes joints and renders movement impossible, with no current effective prevention or cure available. Prompt genetic counseling is important in families with FOP due to its autosomal dominant inheritance.
JCR-JOURNAL OF CLINICAL RHEUMATOLOGY
(2021)
Review
Pharmacology & Pharmacy
Chloe N. Thomas, Dawn A. Sim, Wen Hwa Lee, Nada Alfahad, Andrew D. Dick, Alastair K. Denniston, Lisa J. Hill
Summary: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world, with the need for new therapies to address disease progression and treatment challenges at different stages.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Ophthalmology
Susan P. Mollan, Dun Jack Fu, Ching-Yi Chuo, Jacqueline G. Gannon, Wen Hwa Lee, J. Jill Hopkins, Cian Hughes, Alastair K. Denniston, Pearse A. Keane, Ronald Cantrell
Summary: By combining data from a national digital health data repository with historical clinical trial data, we demonstrate an enhanced predictive modeling in nAMD. The detrimental effects of prolonged treatment delay should motivate healthcare providers to support nAMD patients in accessing care in safe environments.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Rheumatology
Mark C. Hwang, MinJae Lee, Lianne S. Gensler, Matthew A. Brown, Amirali Tahanan, Mohammad H. Rahbar, Theresa Hunter, Mingyan Shan, Mariko L. Ishimori, John D. Reveille, Michael H. Weisman, Thomas J. Learch
Summary: This study identified four distinct patterns of spinal disease progression in ankylosing spondylitis patients. Factors associated with higher spinal disease burden groups include male gender, longer disease duration, elevated CRP and smoking history. Independent confirmation in other AS cohorts is needed to confirm these radiographic patterns.
Letter
Rheumatology
Zhixiu Li, Mohammad K. Khan, Peter M. Villiger, Sjef van der Linden, Matthew A. Brown, Muhammad A. Khan
ARTHRITIS CARE & RESEARCH
(2022)
Article
Ophthalmology
Krishna M. Gokhale, Nicola J. Adderley, Anuradhaa Subramanian, Wen Hwa Lee, Diana Han, Jesse Coker, Tasanee Braithwaite, Alastair K. Denniston, Pearse A. Keane, Krishnarajah Nirantharakumar
Summary: This study aimed to explore the relationship between metformin use and the development of AMD in patients with type 2 diabetes in the UK. The results showed that there was no association between the use of metformin and the risk of developing AMD, regardless of whether other antidiabetic medications were also used.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Genetics & Heredity
Aideen M. McInerney-Leo, Jennifer West, Bettina Meiser, Malcolm West, Maree R. Toombs, Matthew A. Brown, Emma L. Duncan
Summary: This study explores the physical and psychological impacts of MFS on Aboriginal Australians. It found that MFS presents significant challenges in daily living, especially severe vision impairment contributing to social exclusion and psychological distress. As individuals age, concerns shift towards cardiac complications.
JOURNAL OF GENETIC COUNSELING
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Philip S. Jones, Steven van Helden, Volkhart Min-Jian Li, Ton Vries, Jon S. B. de Vlieger
Summary: The European Lead Factory combines assets and experience from major pharma with innovation and agility of academia and SMEs in a collaborative platform to expand access to high-throughput screening. With many successes heading towards the clinic, the organization is broadening its approach to screening and partnering.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Article
Rheumatology
Sjef M. van der Linden, Muhammad Asim Khan, Zhixiu Li, Heinz Baumberger, Hermine van Zandwijk, Kazim Khan, Peter M. Villiger, Matthew A. Brown
Summary: The occurrence of acute anterior uveitis (AAU) among first-degree relatives (FDRs) of axial spondyloarthritis (axSpA) patients should prompt screening for axSpA. The co-occurrence of chronic inflammatory back pain (CIBP) and pain/discomfort in the thoracic spine and anterior chest wall can further enhance clinical suspicion of axSpA among these FDRs.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Rheumatology
Zhixiu Li, Sjef M. van der Linden, Muhammad Asim Khan, Heinz Baumberger, Hermine van Zandwijk, Mohammad Kazim Khan, Peter M. Villiger, Matthew A. Brown
Summary: The objective of this study is to assess heterogeneity in axial spondyloarthritis (axSpA) and its sources. The results suggest that women clinically diagnosed with axSpA but without radiographic sacroiliitis have distinct characteristics compared to men with non-radiographic axSpA.
Letter
Genetics & Heredity
Matthew A. Brown, Christopher Wigley, Susan Walker, Deborah Lancaster, Augusto Rendon, Richard Scott
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Rheumatology
Sjef M. van der Linden, Muhammad Asim Khan, Zhixiu Li, Heinz Baumberger, Hermine van Zandwijk, Mohammad Kazim Khan, Peter M. Villiger, Matthew A. Brown
Summary: The lifetime recurrence risk of axSpA is substantial for HLA-B27(+) FDRs, and disease severity and the gender of the proband's children are associated with the risk of developing axSpA.
Article
Rheumatology
Lauren K. Ridley, Mark C. Hwang, John D. Reveille, Lianne S. Gensler, Mariko L. Ishimori, Matthew A. Brown, Mohammad H. Rahbar, Amirali Tahanan, Michael M. Ward, Michael H. Weisman, Thomas J. Learch
Summary: This study investigated a subgroup of patients with ankylosing spondylitis (AS) who had long-standing disease and fused sacroiliac (SI) joints and found that females and males with early symptom onset had less radiographic damage in the SI joints. All 23 patients without syndesmophytes were HLA-B27 positive.
JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
Jose Garrido-Mesa, Matthew A. Brown
Summary: The expansion of a restricted pool of CD8 lymphocytes is commonly found in AS patients, but only in a small proportion of healthy HLA-B27 carriers. These findings strongly support the theory that AS is driven by the presentation of antigenic peptides to the adaptive immune system by HLA-B27.
CURRENT RHEUMATOLOGY REPORTS
(2022)
Article
Cell Biology
Parinya Samakkarnthai, Dominik Saul, Lei Zhang, Zaira Aversa, Madison L. Doolittle, Jad G. Sfeir, Japneet Kaur, Elizabeth J. Atkinson, James R. Edwards, Graham G. Russell, Robert J. Pignolo, James L. Kirkland, Tamar Tchkonia, Laura J. Niedernhofer, David G. Monroe, Nathan K. Lebrasseur, Joshua N. Farr, Paul D. Robbins, Sudeep Khosla
Summary: In addition to reducing fracture risk, zoledronic acid has been found to extend lifespan and healthspan in animals. The study suggests that the non-skeletal actions of zoledronic acid could be due to its ability to kill senescent cells and inhibit the secretion of harmful substances from these cells. These findings highlight the potential of zoledronic acid in anti-aging therapy.
Review
Genetics & Heredity
Xiu-Feng Huang, Matthew A. Brown
Summary: Uveitis, the most common form of intraocular inflammatory disease, can be classified into infectious and non-infectious types. Non-infectious uveitis includes various conditions such as AAU, BD, VKH disease, BSCR, and sarcoid uveitis, with genetic and environmental factors playing important roles in its pathogenesis. Studies have identified strong associations with HLA in uveitis, leading to potential future research directions.
GENES AND IMMUNITY
(2022)