Lukas Zierke, Marcel Gischke, Q. Tran, A. Aghdassi
Hereditary and autoimmune pancreatitis are two rare forms of inflammatory pancreatic disorders. Both share similarities with acute, acute recurrent, and chronic pancreatitis. Regarding their pathogenesis, the premature activation of the digestive protease trypsinogen and the infiltration of inflammatory cells such as polymorphonuclear leukocytes and macrophages into the pancreas are highly relevant and can reciprocally amplify inflammation. Neutrophil serine proteases are the main components of neutrophil granulocytes and have different pro-inflammatory effects in many diseases. However, their role in pancreatitis is still limited. This section focuses on known findings regarding the role of this group of enzymes in hereditary and autoimmune pancreatitis.
{"title":"Pathogenesis of autoimmune and hereditary pancreatitis with a focus on neutrophil granulocytes and neutrophil serine proteases","authors":"Lukas Zierke, Marcel Gischke, Q. Tran, A. Aghdassi","doi":"10.20517/rdodj.2022.17","DOIUrl":"https://doi.org/10.20517/rdodj.2022.17","url":null,"abstract":"Hereditary and autoimmune pancreatitis are two rare forms of inflammatory pancreatic disorders. Both share similarities with acute, acute recurrent, and chronic pancreatitis. Regarding their pathogenesis, the premature activation of the digestive protease trypsinogen and the infiltration of inflammatory cells such as polymorphonuclear leukocytes and macrophages into the pancreas are highly relevant and can reciprocally amplify inflammation. Neutrophil serine proteases are the main components of neutrophil granulocytes and have different pro-inflammatory effects in many diseases. However, their role in pancreatitis is still limited. This section focuses on known findings regarding the role of this group of enzymes in hereditary and autoimmune pancreatitis.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"25 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Zanello, D. Ardigò, Florence Guillot, A. Jonker, Oxana Iliach, H. Nabarette, Daniel O’Connor, V. Hivert
Drug repurposing represents a real opportunity to address unmet needs and improve the lives of rare disease patients. It is often presented as a faster, safer and cheaper path for bringing drugs into new indications. However, several economic, regulatory and scientific barriers can impede the successful repurposing of drugs for rare diseases. The International Rare Diseases Research Consortium (IRDiRC) set up the Task Force on Sustainable Models in Drug Repurposing with the objective of identifying key factors for achieving sustainable repurposing approaches in rare diseases. In order to help inform expert opinion, the Task Force investigated six cases of medicinal products repurposed into new rare indications and four cases of ongoing development programs. A questionnaire addressing the major steps of the repurposing approach was developed by the Task Force and sent to contact points of the organizations. In addition, interviews were conducted with the relevant organization representatives to conduct a deeper dive into the sustainability of the repurposing approach for each of the selected cases. Based on the collective experience of the members of the Task Force and the output from the questionnaires/interviews, we have identified ten key factors that should be considered by those embarking on repurposing projects. These factors include the identification of unmet patient needs and partnership with patients, collection of evidence concerning disease prevalence, patient numbers, drug pharmacology and disease etiology, drug industrial property status, off-label or compounding use, data from past clinical studies and needs for extended non-clinical and clinical studies. The development of a collaborative funding framework and early discussion with regulators and payers are additional factors to implement early in the development of sustainable drug repurposing projects.
{"title":"Sustainable approaches for drug repurposing in rare diseases: recommendations from the IRDiRC Task Force","authors":"G. Zanello, D. Ardigò, Florence Guillot, A. Jonker, Oxana Iliach, H. Nabarette, Daniel O’Connor, V. Hivert","doi":"10.20517/rdodj.2023.04","DOIUrl":"https://doi.org/10.20517/rdodj.2023.04","url":null,"abstract":"Drug repurposing represents a real opportunity to address unmet needs and improve the lives of rare disease patients. It is often presented as a faster, safer and cheaper path for bringing drugs into new indications. However, several economic, regulatory and scientific barriers can impede the successful repurposing of drugs for rare diseases. The International Rare Diseases Research Consortium (IRDiRC) set up the Task Force on Sustainable Models in Drug Repurposing with the objective of identifying key factors for achieving sustainable repurposing approaches in rare diseases. In order to help inform expert opinion, the Task Force investigated six cases of medicinal products repurposed into new rare indications and four cases of ongoing development programs. A questionnaire addressing the major steps of the repurposing approach was developed by the Task Force and sent to contact points of the organizations. In addition, interviews were conducted with the relevant organization representatives to conduct a deeper dive into the sustainability of the repurposing approach for each of the selected cases. Based on the collective experience of the members of the Task Force and the output from the questionnaires/interviews, we have identified ten key factors that should be considered by those embarking on repurposing projects. These factors include the identification of unmet patient needs and partnership with patients, collection of evidence concerning disease prevalence, patient numbers, drug pharmacology and disease etiology, drug industrial property status, off-label or compounding use, data from past clinical studies and needs for extended non-clinical and clinical studies. The development of a collaborative funding framework and early discussion with regulators and payers are additional factors to implement early in the development of sustainable drug repurposing projects.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
There are different approaches to drug repurposing (DR) depending on the status of the repurposable drug/molecule (approved, investigational, withdrawn, shelved), the context, and the stakeholders involved. The purpose of this perspective paper is to highlight the complexity of academia-industry collaborations in DR for rare diseases and go beyond stereotypes to consider realistic and mutually reinforcing cooperation among various stakeholders, including not only academia and industry but also regulators, legal experts, and payers, leading to benefits for patients with unmet medical needs. Key questions are addressed through the presentation of select DR case studies. Some ongoing and promising European and international initiatives are introduced and some recommendations are proposed.
{"title":"Connecting academia and industry for innovative drug repurposing in rare diseases: it is worth a try","authors":"C. Fétro","doi":"10.20517/rdodj.2023.06","DOIUrl":"https://doi.org/10.20517/rdodj.2023.06","url":null,"abstract":"There are different approaches to drug repurposing (DR) depending on the status of the repurposable drug/molecule (approved, investigational, withdrawn, shelved), the context, and the stakeholders involved. The purpose of this perspective paper is to highlight the complexity of academia-industry collaborations in DR for rare diseases and go beyond stereotypes to consider realistic and mutually reinforcing cooperation among various stakeholders, including not only academia and industry but also regulators, legal experts, and payers, leading to benefits for patients with unmet medical needs. Key questions are addressed through the presentation of select DR case studies. Some ongoing and promising European and international initiatives are introduced and some recommendations are proposed.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Klugmann, Alexandra K. Suchowerska, G. Housley, Dominik Fröhlich
Aminoacyl-tRNA synthetases are essential, non-redundant enzymes that catalyze the charging of tRNAs with their cognate amino acids. This reaction is a prerequisite for protein translation in all cells. Mutations in human aminoacyl-tRNA synthetases are often associated with defects of the peripheral and central nervous system and are the underlying cause of many rare diseases including neuropathies and leukodystrophies. A comprehensive understanding of aminoacyl-tRNA synthetase expression domains is key to understanding these disorders and developing novel targeted treatment strategies. Here, we describe histological and biochemical methods to analyze the expression pattern of the aspartyl-tRNA synthetase AspRS in human post-mortem brain tissue. The same methods can readily be applied to other members of the aminoacyl-tRNA synthetase superfamily or, more generally, to other cytosolic proteins in the human brain.
{"title":"Histological and biochemical methods to assess aminoacyl-tRNA synthetase expression in human post-mortem brain tissue","authors":"M. Klugmann, Alexandra K. Suchowerska, G. Housley, Dominik Fröhlich","doi":"10.20517/rdodj.2023.05","DOIUrl":"https://doi.org/10.20517/rdodj.2023.05","url":null,"abstract":"Aminoacyl-tRNA synthetases are essential, non-redundant enzymes that catalyze the charging of tRNAs with their cognate amino acids. This reaction is a prerequisite for protein translation in all cells. Mutations in human aminoacyl-tRNA synthetases are often associated with defects of the peripheral and central nervous system and are the underlying cause of many rare diseases including neuropathies and leukodystrophies. A comprehensive understanding of aminoacyl-tRNA synthetase expression domains is key to understanding these disorders and developing novel targeted treatment strategies. Here, we describe histological and biochemical methods to analyze the expression pattern of the aspartyl-tRNA synthetase AspRS in human post-mortem brain tissue. The same methods can readily be applied to other members of the aminoacyl-tRNA synthetase superfamily or, more generally, to other cytosolic proteins in the human brain.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The recent description of a cohort with both adults and children harboring biallelic pathogenic variants of CUBN changed the paradigm of the management of isolated proteinuria. Indeed, the detection of proteinuria in a patient, regardless of age, often leads to an exhaustive check-up including kidney biopsy but also the prescription of renin-angiotensin system (RAS) blockers to slow the progression of kidney disease. Patients with CUBN variants have nondetrimental proteinuria and are non-responsive to RAS blockers. We herein describe 2 siblings treated for isolated proteinuria for several years, eventually diagnosed with CUBN biallelic pathogenic variants (c.703 C > T and c.10363-3A > G). We review the physio-pathological mechanisms of this newly discovered disease and discuss implications for clinical management.
{"title":"Biallelic cubilin pathogenic variants as a cause of « benign » proteinuria: implications for clinical management","authors":"V. Gillion, K. Dahan, N. Godefroid","doi":"10.20517/rdodj.2022.23","DOIUrl":"https://doi.org/10.20517/rdodj.2022.23","url":null,"abstract":"The recent description of a cohort with both adults and children harboring biallelic pathogenic variants of CUBN changed the paradigm of the management of isolated proteinuria. Indeed, the detection of proteinuria in a patient, regardless of age, often leads to an exhaustive check-up including kidney biopsy but also the prescription of renin-angiotensin system (RAS) blockers to slow the progression of kidney disease. Patients with CUBN variants have nondetrimental proteinuria and are non-responsive to RAS blockers. We herein describe 2 siblings treated for isolated proteinuria for several years, eventually diagnosed with CUBN biallelic pathogenic variants (c.703 C > T and c.10363-3A > G). We review the physio-pathological mechanisms of this newly discovered disease and discuss implications for clinical management.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, accumulating evidence has shown that pulmonary arterial hypertension (PAH) has a strong underlying inflammatory component. Vascular remodeling, a common pathology observed in all forms of pulmonary hypertension (PH), is accompanied by a pronounced accumulation of leukocytes around and within the vessels. Proteolytic products of immune cells, particularly neutrophil and mast cell serine proteases, have been shown to play a central pathogenic role in vascular remodeling and PAH development. Serine proteases are involved in many aspects of the inflammatory response, such as extracellular matrix degradation, regulation of bioavailability of cytokines, chemokines, and growth factors, and dysregulation of their activity can have devastating consequences. In this review, we will focus on immune dysregulation in PAH and shed light on the pro-inflammatory role of serine proteases in vascular pathology observed in the context of this disease.
{"title":"Immune cell-derived serine protease as pathogenic drivers of vascular remodeling in pulmonary arterial hypertension","authors":"Izabela Borek, G. Kwapiszewska","doi":"10.20517/rdodj.2022.20","DOIUrl":"https://doi.org/10.20517/rdodj.2022.20","url":null,"abstract":"In recent years, accumulating evidence has shown that pulmonary arterial hypertension (PAH) has a strong underlying inflammatory component. Vascular remodeling, a common pathology observed in all forms of pulmonary hypertension (PH), is accompanied by a pronounced accumulation of leukocytes around and within the vessels. Proteolytic products of immune cells, particularly neutrophil and mast cell serine proteases, have been shown to play a central pathogenic role in vascular remodeling and PAH development. Serine proteases are involved in many aspects of the inflammatory response, such as extracellular matrix degradation, regulation of bioavailability of cytokines, chemokines, and growth factors, and dysregulation of their activity can have devastating consequences. In this review, we will focus on immune dysregulation in PAH and shed light on the pro-inflammatory role of serine proteases in vascular pathology observed in the context of this disease.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Persico, A. Ricciardello, F. Cucinotta, L. Turriziani, G. Calabrese, P. Tomaiuolo, T. Di Bella, F. Bellomo, M. Boncoddo, G. Turturo, S. Mirabelli, Lisa Asta, F. Banchelli, Riccardo Cuoghi Costantini, Roberto D’amico
Aim: Defective mitochondrial function and increased oxidative stress have been documented in Autism Spectrum Disorder (ASD) and Phelan-McDermid syndrome (PMS), one of the best-known monogenic forms of ASD. The purpose of this exploratory, double-blind, randomized cross-over trial (RCT) is to verify the efficacy and safety of a “metabolic support therapy” (MST) in PMS, while defining the experimental methodology most apt at maximizing sensitivity and reliability. Methods: A total of 31 PMS patients completed 4 months of Coenzyme Q10 (50/100 mg b.i.d.) + vitamin E (30/60 mg/d) + polyvitamin B ("active compound") vs. 4 months of only Vitamins E and B ("active comparator"). To explore their sensitivity and reliability, four primary outcome measures were used: VABS, CARS, CGI-I, and VAS. Secondary outcome measures span adaptive behaviors, social cognition, autism, problem behaviors, quality of life (QoL), communication, and comorbidities. Results: CoQ10+vit. E and B yielded significantly greater improvement in several measures of cognition and adaptive functioning, motor skills, and stereotypic behaviors compared to vit. E and B only. Maternal QoL was especially improved in the presence of CoQ10 (P < 0.004). Time x Treatment interactions in CGI-I and VAS "restricted interests" scores support positive contributions also by vitamins E and B. Side effects, including hyperactivity, insomnia, and irritability, were mild, rare, and did not differ between treatment periods. Conclusion: MST may produce small-to-moderate improvement, especially in motor skills, social motivation, adaptive behaviors, responsiveness to environmental stimulation, and stereotypic behaviors in up to approximately 70% of PMS patients. A targeted confirmatory RCT contrasting Q10+vit E and B vs. inactive placebo is now warranted.
{"title":"Coenzyme Q10, Vitamin E and Polyvitamin B: an exploratory double-blind randomized cross-over study in Phelan-McDermid Syndrome","authors":"A. Persico, A. Ricciardello, F. Cucinotta, L. Turriziani, G. Calabrese, P. Tomaiuolo, T. Di Bella, F. Bellomo, M. Boncoddo, G. Turturo, S. Mirabelli, Lisa Asta, F. Banchelli, Riccardo Cuoghi Costantini, Roberto D’amico","doi":"10.20517/rdodj.2023.08","DOIUrl":"https://doi.org/10.20517/rdodj.2023.08","url":null,"abstract":"Aim: Defective mitochondrial function and increased oxidative stress have been documented in Autism Spectrum Disorder (ASD) and Phelan-McDermid syndrome (PMS), one of the best-known monogenic forms of ASD. The purpose of this exploratory, double-blind, randomized cross-over trial (RCT) is to verify the efficacy and safety of a “metabolic support therapy” (MST) in PMS, while defining the experimental methodology most apt at maximizing sensitivity and reliability. Methods: A total of 31 PMS patients completed 4 months of Coenzyme Q10 (50/100 mg b.i.d.) + vitamin E (30/60 mg/d) + polyvitamin B (\"active compound\") vs. 4 months of only Vitamins E and B (\"active comparator\"). To explore their sensitivity and reliability, four primary outcome measures were used: VABS, CARS, CGI-I, and VAS. Secondary outcome measures span adaptive behaviors, social cognition, autism, problem behaviors, quality of life (QoL), communication, and comorbidities. Results: CoQ10+vit. E and B yielded significantly greater improvement in several measures of cognition and adaptive functioning, motor skills, and stereotypic behaviors compared to vit. E and B only. Maternal QoL was especially improved in the presence of CoQ10 (P < 0.004). Time x Treatment interactions in CGI-I and VAS \"restricted interests\" scores support positive contributions also by vitamins E and B. Side effects, including hyperactivity, insomnia, and irritability, were mild, rare, and did not differ between treatment periods. Conclusion: MST may produce small-to-moderate improvement, especially in motor skills, social motivation, adaptive behaviors, responsiveness to environmental stimulation, and stereotypic behaviors in up to approximately 70% of PMS patients. A targeted confirmatory RCT contrasting Q10+vit E and B vs. inactive placebo is now warranted.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angelika Mazur, J. Skrzeczynska-Moncznik, P. Majewski, J. Cichy
Congenital neutropenia, which refers to an inherited deficiency in neutrophils, is a rare pathologic condition that affects approximately 0.0001-0.0009% of the general population. While congenital neutropenia can result from mutations in approximately 30 genes, its leading cause is gain-of-function mutations in the ELANE gene, which encodes the neutrophil granule serine protease, neutrophil elastase. This review focuses on established and novel concepts in the genetic, molecular and cellular mechanisms underlying neutrophil elastase-dependent neutropenia, and discusses possible new avenues for neutropenia research as well as potential novel treatment options that target pathogenic elastase variants.
{"title":"Elastase-dependent congenital neutropenia","authors":"Angelika Mazur, J. Skrzeczynska-Moncznik, P. Majewski, J. Cichy","doi":"10.20517/rdodj.2022.12","DOIUrl":"https://doi.org/10.20517/rdodj.2022.12","url":null,"abstract":"Congenital neutropenia, which refers to an inherited deficiency in neutrophils, is a rare pathologic condition that affects approximately 0.0001-0.0009% of the general population. While congenital neutropenia can result from mutations in approximately 30 genes, its leading cause is gain-of-function mutations in the ELANE gene, which encodes the neutrophil granule serine protease, neutrophil elastase. This review focuses on established and novel concepts in the genetic, molecular and cellular mechanisms underlying neutrophil elastase-dependent neutropenia, and discusses possible new avenues for neutropenia research as well as potential novel treatment options that target pathogenic elastase variants.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rare diseases occur in their large majority from a genetic cause, which makes them good candidates for genetic RNA drugs. The basic concepts, principles, mechanisms of action and chemical optimizations of synthetic antisense oligonucleotides (ASO) and small interfering RNA (siRNA) are illustrated. These drugs act either by leading to RNA degradation, or as steric blockers of RNA translation, microRNA antagonists, splicing modulators or inducers of exon skipping. Chemical modifications and delivery techniques differ and are adapted to their distinct functions. The successes, potential, and challenges of synthetic RNA drugs are illustrated for several muscular and neuromuscular diseases: Duchenne muscular dystrophy, spinal muscular atrophy, transthyretin amyloidosis, Type 1 myotonic dystrophy, centronuclear myopathy, oculopharyngeal muscular dystrophy.
{"title":"RNA antisense and silencing strategies using synthetic drugs for rare muscular and neuromuscular diseases","authors":"D. Scherman","doi":"10.20517/rdodj.2023.01","DOIUrl":"https://doi.org/10.20517/rdodj.2023.01","url":null,"abstract":"Rare diseases occur in their large majority from a genetic cause, which makes them good candidates for genetic RNA drugs. The basic concepts, principles, mechanisms of action and chemical optimizations of synthetic antisense oligonucleotides (ASO) and small interfering RNA (siRNA) are illustrated. These drugs act either by leading to RNA degradation, or as steric blockers of RNA translation, microRNA antagonists, splicing modulators or inducers of exon skipping. Chemical modifications and delivery techniques differ and are adapted to their distinct functions. The successes, potential, and challenges of synthetic RNA drugs are illustrated for several muscular and neuromuscular diseases: Duchenne muscular dystrophy, spinal muscular atrophy, transthyretin amyloidosis, Type 1 myotonic dystrophy, centronuclear myopathy, oculopharyngeal muscular dystrophy.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Priscille Donate, Michelle Rivera-Davila, Siddharth K Prakash
Aim: Turner Syndrome (TS) is caused by partial or complete absence of the second sex chromosome in a phenotypic female. TS is associated with recognizable congenital anomalies and chronic health conditions. The principal objective of this study was to evaluate the health-related knowledge and insight of participants.
Methods: In 2015, we founded the UTHealth Turner Syndrome Research Registry for longitudinal follow-up of individuals with TS. Study participants were recruited from UTHealth Houston clinics and the Turner Syndrome Society of the United States. Participants completed a questionnaire about demographics, karyotype, congenital anomalies, health history, frequency of contact with care providers, and knowledge of care providers about TS.
Results: Forty percent of registry participants indicated that they did not know their karyotypes. Knowledge of karyotype, which can predict clinical outcomes in TS, markedly varied by self-reported race and ethnicity but not by age. Participants also reported significant gaps in routine medical and gynecologic care.
Conclusion: We identified knowledge gaps and health disparities that could benefit from improved provider and patient education.
{"title":"Health disparities in Turner Syndrome: UTHealth Turner Syndrome Research Registry.","authors":"Priscille Donate, Michelle Rivera-Davila, Siddharth K Prakash","doi":"10.20517/rdodj.2023.02","DOIUrl":"https://doi.org/10.20517/rdodj.2023.02","url":null,"abstract":"<p><strong>Aim: </strong>Turner Syndrome (TS) is caused by partial or complete absence of the second sex chromosome in a phenotypic female. TS is associated with recognizable congenital anomalies and chronic health conditions. The principal objective of this study was to evaluate the health-related knowledge and insight of participants.</p><p><strong>Methods: </strong>In 2015, we founded the UTHealth Turner Syndrome Research Registry for longitudinal follow-up of individuals with TS. Study participants were recruited from UTHealth Houston clinics and the Turner Syndrome Society of the United States. Participants completed a questionnaire about demographics, karyotype, congenital anomalies, health history, frequency of contact with care providers, and knowledge of care providers about TS.</p><p><strong>Results: </strong>Forty percent of registry participants indicated that they did not know their karyotypes. Knowledge of karyotype, which can predict clinical outcomes in TS, markedly varied by self-reported race and ethnicity but not by age. Participants also reported significant gaps in routine medical and gynecologic care.</p><p><strong>Conclusion: </strong>We identified knowledge gaps and health disparities that could benefit from improved provider and patient education.</p>","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"2 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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