Pub Date : 2021-04-03DOI: 10.1080/21678707.2021.1913121
J. Bang, Jong Hyuk Lee
ABSTRACT Introduction: In addition to some countries facing challenges regarding patients with rare diseases, it has also become an important international topic. Through the efforts of many nations around the world toward providing benefits for the development of orphan drugs to improve the right to treatment of patients with rare diseases, various orphan drugs have been launched in the market. However, controversial issues such as impact on budgets due to high prices and concerns about the uncertainty of clinical outcomes are being raised. For this review, the official websites of government agencies related to the Korean national health insurance were investigated. Areas covered: This paper reviews key factors that should be considered in the process of development, regulation, and market access of orphan drugs in South Korea with a particular focus on the pricing and reimbursement review process. Expert opinion: It is necessary to understand the pricing and reimbursement system of orphan drugs in terms of regulations and market access from the perspective of stakeholders, namely research and development companies, patients, policymakers, and physicians. Stakeholder discussions regarding value-based pricing methodologies such as new outcome-based ris-sharing agreement schemes and multi–criteria decision analysis should be conducted more prospectively.
{"title":"The national drug formulary listing process for orphan drugs in South Korea: narrative review focused on pricing and reimbursement pathways","authors":"J. Bang, Jong Hyuk Lee","doi":"10.1080/21678707.2021.1913121","DOIUrl":"https://doi.org/10.1080/21678707.2021.1913121","url":null,"abstract":"ABSTRACT Introduction: In addition to some countries facing challenges regarding patients with rare diseases, it has also become an important international topic. Through the efforts of many nations around the world toward providing benefits for the development of orphan drugs to improve the right to treatment of patients with rare diseases, various orphan drugs have been launched in the market. However, controversial issues such as impact on budgets due to high prices and concerns about the uncertainty of clinical outcomes are being raised. For this review, the official websites of government agencies related to the Korean national health insurance were investigated. Areas covered: This paper reviews key factors that should be considered in the process of development, regulation, and market access of orphan drugs in South Korea with a particular focus on the pricing and reimbursement review process. Expert opinion: It is necessary to understand the pricing and reimbursement system of orphan drugs in terms of regulations and market access from the perspective of stakeholders, namely research and development companies, patients, policymakers, and physicians. Stakeholder discussions regarding value-based pricing methodologies such as new outcome-based ris-sharing agreement schemes and multi–criteria decision analysis should be conducted more prospectively.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"105 - 112"},"PeriodicalIF":0.8,"publicationDate":"2021-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1913121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46501682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-04-03DOI: 10.1080/21678707.2021.1927700
G. Mulinacci, A. Palermo, P. Invernizzi, M. Carbone
ABSTRACT Introduction: Primary Biliary Cholangitis (PBC) is a chronic liver disease characterized by intrahepatic biliary destruction and progressive cholestasis potentially leading to end-stage liver disease and its associated complications. As for many chronic disorders, the risk of disease progression in PBC varies between patients. This has fostered the identification of disease tags defining the trajectory of the disease course. Areas covered: In this review, authors report the evidence-based parameters associated with outcomes in PBC, after an extensive literature search of the PubMed electronic database. Expert opinion: Several prognostic tools including clinical and biochemical disease parameters have been proposed. In the era of the omics science and digital innovation, biomarker discovery has sped up. Extensive data and sample collection of well-phenotyped cohorts of patients with longitudinal follow-up will guarantee an extraordinary opportunity to integrate molecular phenotyping into the clinic, thus promoting a personalized care of patients with PBC. Finally, we emphasize the need to leverage a therapeutic window of opportunity in PBC bringing a paradigm shift toward early intervention with combination therapies in individuals with a more severe phenotype to reach a deeper disease control and halt disease progression.
{"title":"Old and novel prognostic biomarkers in primary biliary cholangitis","authors":"G. Mulinacci, A. Palermo, P. Invernizzi, M. Carbone","doi":"10.1080/21678707.2021.1927700","DOIUrl":"https://doi.org/10.1080/21678707.2021.1927700","url":null,"abstract":"ABSTRACT Introduction: Primary Biliary Cholangitis (PBC) is a chronic liver disease characterized by intrahepatic biliary destruction and progressive cholestasis potentially leading to end-stage liver disease and its associated complications. As for many chronic disorders, the risk of disease progression in PBC varies between patients. This has fostered the identification of disease tags defining the trajectory of the disease course. Areas covered: In this review, authors report the evidence-based parameters associated with outcomes in PBC, after an extensive literature search of the PubMed electronic database. Expert opinion: Several prognostic tools including clinical and biochemical disease parameters have been proposed. In the era of the omics science and digital innovation, biomarker discovery has sped up. Extensive data and sample collection of well-phenotyped cohorts of patients with longitudinal follow-up will guarantee an extraordinary opportunity to integrate molecular phenotyping into the clinic, thus promoting a personalized care of patients with PBC. Finally, we emphasize the need to leverage a therapeutic window of opportunity in PBC bringing a paradigm shift toward early intervention with combination therapies in individuals with a more severe phenotype to reach a deeper disease control and halt disease progression.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"123 - 131"},"PeriodicalIF":0.8,"publicationDate":"2021-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1927700","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42490044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-04DOI: 10.1080/21678707.2021.1904395
A. Tomelleri, C. Campochiaro, G. de Luca, N. Farina, G. Cavalli, L. Dagna
ABSTRACT Introduction Still’s disease is a systemic, non-monogenic autoinflammatory condition affecting both children and adolescents (systemic juvenile idiopathic arthritis, sJIA) and adults (adult-onset Still’s disease, AOSD). Its clinical spectrum ranges from mild forms to life-threatening cases. Glucocorticoids represent the first-line therapy, but their chronic use is burdened with significant side effects. Hence, add-on therapy with disease modifying anti-rheumatic drugs and biologic anti-cytokine agents is frequently required, especially in patients with severe and recalcitrant clinical phenotypes. Among the targetable cytokines with a primary role in the pathogenesis of Still’s disease, interleukin-1 has a leading position. Areas covered This review presents the available controlled evidence and observational studies regarding the efficacy and safety of canakinumab, a monoclonal antibody targeting interleukin-1β, in the treatment of Still’s disease. Expert opinion Controlled studies fully support the clinical efficacy of canakinumab in the treatment of patients affected by sJIA. Conversely, strong evidences are still lacking in AOSD patients; nevertheless, its use in the adult population is legitimated by an increasing number of cases series and case reports and by preclinical data linking the pathogenesis of these two diseases. In addition, canakinumab has an excellent safety profile. Its role in preventing and treating macrophage activation syndrome is still debated.
{"title":"Canakinumab injection for the treatment of active Still’s disease, including adult-onset Still’s disease","authors":"A. Tomelleri, C. Campochiaro, G. de Luca, N. Farina, G. Cavalli, L. Dagna","doi":"10.1080/21678707.2021.1904395","DOIUrl":"https://doi.org/10.1080/21678707.2021.1904395","url":null,"abstract":"ABSTRACT Introduction Still’s disease is a systemic, non-monogenic autoinflammatory condition affecting both children and adolescents (systemic juvenile idiopathic arthritis, sJIA) and adults (adult-onset Still’s disease, AOSD). Its clinical spectrum ranges from mild forms to life-threatening cases. Glucocorticoids represent the first-line therapy, but their chronic use is burdened with significant side effects. Hence, add-on therapy with disease modifying anti-rheumatic drugs and biologic anti-cytokine agents is frequently required, especially in patients with severe and recalcitrant clinical phenotypes. Among the targetable cytokines with a primary role in the pathogenesis of Still’s disease, interleukin-1 has a leading position. Areas covered This review presents the available controlled evidence and observational studies regarding the efficacy and safety of canakinumab, a monoclonal antibody targeting interleukin-1β, in the treatment of Still’s disease. Expert opinion Controlled studies fully support the clinical efficacy of canakinumab in the treatment of patients affected by sJIA. Conversely, strong evidences are still lacking in AOSD patients; nevertheless, its use in the adult population is legitimated by an increasing number of cases series and case reports and by preclinical data linking the pathogenesis of these two diseases. In addition, canakinumab has an excellent safety profile. Its role in preventing and treating macrophage activation syndrome is still debated.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"77 - 86"},"PeriodicalIF":0.8,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1904395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48478222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-04DOI: 10.1080/21678707.2021.1898371
T. Rezk, M. Fontana, J. Gillmore
ABSTRACT Introduction: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal infiltrative cardiomyopathy (ATTR-CM) characterized by congestive cardiac failure, often with preserved left ventricular ejection fraction, and significant risk of conduction disease. Diagnosis is often delayed or missed due to poor specificity of echocardiography and the historical requirement for a histological diagnosis, frequently an endomyocardial biopsy. Areas covered: Following a detailed literature review focusing on peer reviewed articles (Pubmed, Cochrane Library, Google Scholar), from 1995 to 2020, alongside international diagnostic guidelines and expert opinion in the field, this article will explore the current non-invasive diagnostic criteria for ATTR-CM including the role of transthoracic echocardiography, cardiac MRI, bone scintigraphy, and assessment for exclusion of a clonal dyscrasia. Expert opinion: ATTR-CM is an emerging and increasingly diagnosed cause of heart failure, particularly in the elderly. Promising novel therapies make accurate and swift diagnosis of the disease vital. With the increasing use of cardiac MRI to investigate cardiomyopathy and repurposing of technetium-labeledbone scintigraphy, clinicians are now often able to diagnose ATTR-CM without recourse to an endomyocardial biopsy.
{"title":"A review of the criteria for non-invasive diagnosis of cardiac transthyretin amyloidosis","authors":"T. Rezk, M. Fontana, J. Gillmore","doi":"10.1080/21678707.2021.1898371","DOIUrl":"https://doi.org/10.1080/21678707.2021.1898371","url":null,"abstract":"ABSTRACT Introduction: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal infiltrative cardiomyopathy (ATTR-CM) characterized by congestive cardiac failure, often with preserved left ventricular ejection fraction, and significant risk of conduction disease. Diagnosis is often delayed or missed due to poor specificity of echocardiography and the historical requirement for a histological diagnosis, frequently an endomyocardial biopsy. Areas covered: Following a detailed literature review focusing on peer reviewed articles (Pubmed, Cochrane Library, Google Scholar), from 1995 to 2020, alongside international diagnostic guidelines and expert opinion in the field, this article will explore the current non-invasive diagnostic criteria for ATTR-CM including the role of transthoracic echocardiography, cardiac MRI, bone scintigraphy, and assessment for exclusion of a clonal dyscrasia. Expert opinion: ATTR-CM is an emerging and increasingly diagnosed cause of heart failure, particularly in the elderly. Promising novel therapies make accurate and swift diagnosis of the disease vital. With the increasing use of cardiac MRI to investigate cardiomyopathy and repurposing of technetium-labeledbone scintigraphy, clinicians are now often able to diagnose ATTR-CM without recourse to an endomyocardial biopsy.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"87 - 94"},"PeriodicalIF":0.8,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1898371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47359956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-04DOI: 10.1080/21678707.2021.1903871
H. Coope, L. Parviainen, M. Withe, J. Porter, R. Ross
ABSTRACT Introduction Treatment of pediatric adrenal insufficiency (AI) has been challenging due to a lack of dose and age appropriate hydrocortisone preparations for children. Hydrocortisone granules in capsules for opening (Alkindi) is the only licensed replacement therapy specifically designed for use in pediatric adrenal insufficiency. Areas Covered The high unmet need of the pediatric AI patient population for a licensed, dose-appropriate hydrocortisone formulation and the development and approval of hydrocortisone granules in capsules for opening for pediatric AI. Expert opinion To date, treatment of children with AI has relied on parents or pharmacists crushing tablets of hydrocortisone. Pediatric patients have suffered from over- and under-treatment with poor health outcomes. Hydrocortisone granules in capsules for opening provides accurate, age-appropriate dosing, allowing appropriate dose titration for the growing child. The granule-based formulation is taste masked to hide the bitterness of hydrocortisone, and in clinical trials was well tolerated and easily administered to children. The granules can be administered either directly to the mouth or sprinkled onto soft food or yogurt. Hydrocortisone granules in capsules for opening provides the first licensed treatment option specifically designed for pediatric patients with AI.
{"title":"Hydrocortisone granules in capsules for opening (Alkindi) as replacement therapy in pediatric patients with adrenal insufficiency","authors":"H. Coope, L. Parviainen, M. Withe, J. Porter, R. Ross","doi":"10.1080/21678707.2021.1903871","DOIUrl":"https://doi.org/10.1080/21678707.2021.1903871","url":null,"abstract":"ABSTRACT Introduction Treatment of pediatric adrenal insufficiency (AI) has been challenging due to a lack of dose and age appropriate hydrocortisone preparations for children. Hydrocortisone granules in capsules for opening (Alkindi) is the only licensed replacement therapy specifically designed for use in pediatric adrenal insufficiency. Areas Covered The high unmet need of the pediatric AI patient population for a licensed, dose-appropriate hydrocortisone formulation and the development and approval of hydrocortisone granules in capsules for opening for pediatric AI. Expert opinion To date, treatment of children with AI has relied on parents or pharmacists crushing tablets of hydrocortisone. Pediatric patients have suffered from over- and under-treatment with poor health outcomes. Hydrocortisone granules in capsules for opening provides accurate, age-appropriate dosing, allowing appropriate dose titration for the growing child. The granule-based formulation is taste masked to hide the bitterness of hydrocortisone, and in clinical trials was well tolerated and easily administered to children. The granules can be administered either directly to the mouth or sprinkled onto soft food or yogurt. Hydrocortisone granules in capsules for opening provides the first licensed treatment option specifically designed for pediatric patients with AI.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"67 - 76"},"PeriodicalIF":0.8,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1903871","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48546848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-04DOI: 10.1080/21678707.2021.1904394
Laila S. Al Yazidi, A. Al‐Hatmi
ABSTRACT Introduction Disseminated fusariosis is a serious fungal infection with a high mortality rate among immunocompromised hosts. Management of fusariosis is challenging due to intrinsic resistance to most available antifungal agents. The novel antifungals that are in the pipeline may help to enhance favorable outcome of fusariosis. Clinical trials and animal model studies are required to achieve optimal management of fusariosis. Areas covered This review highlights the available and novel antifungal agents for management of human fusariosis. It also highlights the importance of surgical debridement and reversal of immunosuppression in patients with invasive fusariosis We examine the following databases: Medline, PubMed, and Google Scholar for the following key terms ‘fusariosis', ‘disseminated fusariosis,’ ‘invasive fusariosis,’ and ‘Fusarium.’ Expert opinion Currently, voriconazole or liposomal amphotericin B is the recommended approach for treating invasive fusariosis. Posaconazole is used for salvage therapy. Combination therapy may be used in refractory or severe cases as empiric therapy awaiting results of susceptibility testing. Granulocyte colony stimulating factor is usually used in patients with profound and prolonged neutropenia. Immunosuppressive agents should be reduced when possible. Primary triazole prophylaxis may be considered for high-risk patients, while secondary prophylaxis is recommended in patients with a history of invasive fusariosis requiring immunosuppression.
{"title":"Fusariosis: an update on therapeutic options for management","authors":"Laila S. Al Yazidi, A. Al‐Hatmi","doi":"10.1080/21678707.2021.1904394","DOIUrl":"https://doi.org/10.1080/21678707.2021.1904394","url":null,"abstract":"ABSTRACT Introduction Disseminated fusariosis is a serious fungal infection with a high mortality rate among immunocompromised hosts. Management of fusariosis is challenging due to intrinsic resistance to most available antifungal agents. The novel antifungals that are in the pipeline may help to enhance favorable outcome of fusariosis. Clinical trials and animal model studies are required to achieve optimal management of fusariosis. Areas covered This review highlights the available and novel antifungal agents for management of human fusariosis. It also highlights the importance of surgical debridement and reversal of immunosuppression in patients with invasive fusariosis We examine the following databases: Medline, PubMed, and Google Scholar for the following key terms ‘fusariosis', ‘disseminated fusariosis,’ ‘invasive fusariosis,’ and ‘Fusarium.’ Expert opinion Currently, voriconazole or liposomal amphotericin B is the recommended approach for treating invasive fusariosis. Posaconazole is used for salvage therapy. Combination therapy may be used in refractory or severe cases as empiric therapy awaiting results of susceptibility testing. Granulocyte colony stimulating factor is usually used in patients with profound and prolonged neutropenia. Immunosuppressive agents should be reduced when possible. Primary triazole prophylaxis may be considered for high-risk patients, while secondary prophylaxis is recommended in patients with a history of invasive fusariosis requiring immunosuppression.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"95 - 103"},"PeriodicalIF":0.8,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1904394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43000789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01DOI: 10.1080/21678707.2021.1898370
Josiah D. McCain, D. Chascsa, K. Lindor
ABSTRACT Introduction: Primary sclerosing cholangitis (PSC) is a progressive disease of the bile ducts for which there is no cure. As no therapy has proven to delay this progression, the current focus for these patients is symptom management. In the same vein, the screening for and prevention of diseases for which these patients carry increased risk is an effective part of high-yield care. Areas Covered: A literature search was conducted using the National Center for Biotechnology Information (NCBI) database at the U.S. National Library of Medicine (NLM). Herein is reviewed that literature with special attention to symptom assessment and medical therapies as well as associated disease and screening strategies for patients with PSC. Additionally, some of the previous therapies future directions of treatment are explored. Expert Opinion: Efforts to alter the progression of this disease by targeting the inflammatory process have not produced meaningful results. The limited success of antimicrobial agents raises the question of the role of dysbiosis in PSC and marks a new potential target for therapies to be studied. However, as in many progressive diseases of the liver, fibrosis of the organ remains the irreversible step, and until effective anti-fibrotic agents are developed a definitive cure for PSC may remain elusive.
{"title":"Assessing and managing symptom burden and quality of life in primary sclerosing cholangitis patients","authors":"Josiah D. McCain, D. Chascsa, K. Lindor","doi":"10.1080/21678707.2021.1898370","DOIUrl":"https://doi.org/10.1080/21678707.2021.1898370","url":null,"abstract":"ABSTRACT Introduction: Primary sclerosing cholangitis (PSC) is a progressive disease of the bile ducts for which there is no cure. As no therapy has proven to delay this progression, the current focus for these patients is symptom management. In the same vein, the screening for and prevention of diseases for which these patients carry increased risk is an effective part of high-yield care. Areas Covered: A literature search was conducted using the National Center for Biotechnology Information (NCBI) database at the U.S. National Library of Medicine (NLM). Herein is reviewed that literature with special attention to symptom assessment and medical therapies as well as associated disease and screening strategies for patients with PSC. Additionally, some of the previous therapies future directions of treatment are explored. Expert Opinion: Efforts to alter the progression of this disease by targeting the inflammatory process have not produced meaningful results. The limited success of antimicrobial agents raises the question of the role of dysbiosis in PSC and marks a new potential target for therapies to be studied. However, as in many progressive diseases of the liver, fibrosis of the organ remains the irreversible step, and until effective anti-fibrotic agents are developed a definitive cure for PSC may remain elusive.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"53 - 66"},"PeriodicalIF":0.8,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1898370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42383623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01DOI: 10.1080/21678707.2021.1898373
David A Camp, Michael Gemayel, T. Ciulla
ABSTRACT Introduction: Stargardt macular dystrophy (STGD1), an autosomal recessive disorder, is caused by genetic mutations affecting ATP-Binding Cassette, subfamily A, member 4 (ABCA4). The genetic pathology of STGD1 is complex. Over 1200 disease-causing ABCA4 mutations have been identified which vary in disease severity and geographic/ethnic frequency. Areas Covered: This article provides an introduction to STGD1 and its pathophysiology, including a summary of the normal visual cycle and a description of the ABCA4 protein. The current understanding of the genetic pathology of STGD1 is reviewed, including the relationship between STGD1 and similar diseases, genotype-phenotype correlations of ABCA4-associated retinopathy, types of disease-causing genetic variations, geographic/ethnic considerations, and gene therapy. Expert Opinion: In STGD1, ABCA4 gene mutations and gene variation combinations in individuals can be used to predict phenotype, and can be categorized by severity. However, some cases of STGD1 remain unsolved, and disease severity for many variants remains unknown. Increasing our understanding of the genetic pathology of Stargardt disease will drive the development of future therapies.
{"title":"Understanding the genetic pathology of Stargardt disease: a review of current findings and challenges","authors":"David A Camp, Michael Gemayel, T. Ciulla","doi":"10.1080/21678707.2021.1898373","DOIUrl":"https://doi.org/10.1080/21678707.2021.1898373","url":null,"abstract":"ABSTRACT Introduction: Stargardt macular dystrophy (STGD1), an autosomal recessive disorder, is caused by genetic mutations affecting ATP-Binding Cassette, subfamily A, member 4 (ABCA4). The genetic pathology of STGD1 is complex. Over 1200 disease-causing ABCA4 mutations have been identified which vary in disease severity and geographic/ethnic frequency. Areas Covered: This article provides an introduction to STGD1 and its pathophysiology, including a summary of the normal visual cycle and a description of the ABCA4 protein. The current understanding of the genetic pathology of STGD1 is reviewed, including the relationship between STGD1 and similar diseases, genotype-phenotype correlations of ABCA4-associated retinopathy, types of disease-causing genetic variations, geographic/ethnic considerations, and gene therapy. Expert Opinion: In STGD1, ABCA4 gene mutations and gene variation combinations in individuals can be used to predict phenotype, and can be categorized by severity. However, some cases of STGD1 remain unsolved, and disease severity for many variants remains unknown. Increasing our understanding of the genetic pathology of Stargardt disease will drive the development of future therapies.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"35 - 44"},"PeriodicalIF":0.8,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1898373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45349912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-01DOI: 10.1080/21678707.2021.1903872
F. Fortunato, A. Ferlini
ABSTRACT Introduction: Duchenne muscular dystrophy is a severe, X-linked disease characterized by decreased muscle mass and function in children. Genetic and biochemical research over the years has led to the characterization of the cause and the pathophysiology of the disease. Moreover, the elucidation of genetic mechanisms underlining Duchenne muscular dystrophy has allowed for the design of innovative personalized therapies. Areas covered: The identification of specific, accurate, and sensitive biomarkers is becoming crucial for evaluating muscle disease progression and response to therapies, disease monitoring, and the acceleration of drug development and related regulatory processes. The most promising findings and up-to-date progress in the discovery of proteins or RNA biomarkers and SNPs acting as genetic modifiers are illustrated in this review. Searches were carried out through databases, PubMed, ClinicalTrials.gov. Expert opinion: Authors highlighted the challenges encountered in translating biomarkers into the clinical context and the existing bottlenecks hampering the adoption of biomarkers as surrogate endpoints. These bottlenecks could be overcome by national and international collaborative efforts, multicenter data sharing, and the creation of large cohorts of patients as well as novel statistical tools that can analyze small patient numbers. Finally, collaborations with pharmaceutical companies would greatly increase data sharing, especially from patients who have undergone clinical trials.
{"title":"Clinical application of molecular biomarkers in Duchenne muscular dystrophy: challenges and perspectives","authors":"F. Fortunato, A. Ferlini","doi":"10.1080/21678707.2021.1903872","DOIUrl":"https://doi.org/10.1080/21678707.2021.1903872","url":null,"abstract":"ABSTRACT Introduction: Duchenne muscular dystrophy is a severe, X-linked disease characterized by decreased muscle mass and function in children. Genetic and biochemical research over the years has led to the characterization of the cause and the pathophysiology of the disease. Moreover, the elucidation of genetic mechanisms underlining Duchenne muscular dystrophy has allowed for the design of innovative personalized therapies. Areas covered: The identification of specific, accurate, and sensitive biomarkers is becoming crucial for evaluating muscle disease progression and response to therapies, disease monitoring, and the acceleration of drug development and related regulatory processes. The most promising findings and up-to-date progress in the discovery of proteins or RNA biomarkers and SNPs acting as genetic modifiers are illustrated in this review. Searches were carried out through databases, PubMed, ClinicalTrials.gov. Expert opinion: Authors highlighted the challenges encountered in translating biomarkers into the clinical context and the existing bottlenecks hampering the adoption of biomarkers as surrogate endpoints. These bottlenecks could be overcome by national and international collaborative efforts, multicenter data sharing, and the creation of large cohorts of patients as well as novel statistical tools that can analyze small patient numbers. Finally, collaborations with pharmaceutical companies would greatly increase data sharing, especially from patients who have undergone clinical trials.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":"9 1","pages":"45 - 52"},"PeriodicalIF":0.8,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2021.1903872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43245731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-29DOI: 10.1080/21678707.2021.1927701
Talita Lemos Neves Barreto, Ivana Rocha Raslan, K. Trajano, F. Maggi, J. Pedroso, O. Barsottini, F. Fonseca, Ariel Cordeiro Ferreira, C. Aranda, R. Sarni
ABSTRACT Background: Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder caused by variants of ATM (ataxia telangiectasia mutated) gene. These patients develop metabolic changes over time. We aimed to assess the correlation between neurological features, nutritional status, and metabolic changes in AT patients. Methods: Cross-sectional study with prospective data from 25 AT patients aged 5 to 31 years. Results: Significant correlations were found between the scores on the International Cooperative Ataxia Rating Scale (ICARS) and age (r = 0.748; p < 0.001), gamma glutamyl transferase (GGT) (r = 0.743; p < 0.001), insulin levels (r = 0.520; p = 0.016) and the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index (r = 0.585; p = 0.005) as well as the scores on the Assessment and Rating of Ataxia (SARA) and age (r = 0.704; p < 0.001), GGT (r = 0.701; p < 0.001), insulin levels (r = 0.706; p < 0.001) and HOMA-IR index (r = 0.764; p < 0.001). Conclusions: The relevant correlation between severity of ataxia and disease progression with metabolic changes such as liver function impairment and insulin resistance reinforce the importance to monitoring metabolic changes and evaluate nutritional status in these patients.
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