Therapeutic advances in rare disease最新文献

{"title":"TANGO2 Research Foundation Poster Abstracts 2024 - TANGO2 Family Conference - Disney's Coronado Springs Resort - June 23 - 25, 2024.","authors":"","doi":"10.1177/26330040241264127","DOIUrl":"https://doi.org/10.1177/26330040241264127","url":null,"abstract":"","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241264127"},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303025","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}

{"title":"Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials.","authors":"JayEtta Hecker, Gabrielle Conecker, Chere Chapman, Rebecca Hommer, Natasha N Ludwig, Gunes Sevinc, Sara Te, Mary Wojnaroski, Jenny Downs, Anne T Berg","doi":"10.1177/26330040241249762","DOIUrl":"10.1177/26330040241249762","url":null,"abstract":"<p><p>Existing clinical tools that measure non-seizure outcomes lack the range and granularity needed to capture skills in developmental and epileptic encephalopathy (DEE)-affected individuals who also fall in the severe to profound range of intellectual disability. This effectively excludes those with severe impairments from clinical trials, impeding the ability of sponsors to evaluate disease-modifying therapies (DMTs). The Inchstone Project, an international, patient advocate-led collaboration, brings together leading researchers, clinicians, pharmaceutical companies, and advocates to develop an adapted, validated assessment battery within 5 years. The goal is to support trials of DMTs for the DEEs by providing sufficiently sensitive measurement tools to demonstrate therapeutic efficacy. An initial pilot study administered 7 established assessments to 10 individuals affected by SCN2A-DEE, identifying specific limitations of existing measures and areas for improvement. It was clear that most tools do not account for challenges throughout the DEE population, including vision impairments, significant motor impairments and profound intellectual disability, which need to be accounted for in creating a 'fit-for-purpose' battery for the DEE population. Several novel assessments, including two measures of responsivity developed for use in monitoring recovery after acquired brain injury as well as individualized Goal Attainment Scaling, showed promise in this group. The team also completed a DEE-wide survey with over 270 caregivers documenting their children's abilities and priorities for their improvement from new treatments. The Inchstone team is using this information to evaluate how existing tools might be updated to better capture what is most important to families and measure their child's small but important improvements over time. These efforts are building a coherent picture across multiple DEEs of what domains, or concepts of interest, have the greatest impact on most patients and families. The Inchstone team is on course to adapt non-seizure outcome measures that are (1) sufficiently sensitive to measure small increments of meaningful change ('Inchstones') and (2) applicable to multiple DEE conditions.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"18 ","pages":"26330040241249762"},"PeriodicalIF":0.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443903","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}

{"title":"Corrigendum to \"Proceedings from the MENA Congress for Rare Diseases, 16-19 May 2024, Abu Dhabi, UAE\".","authors":"","doi":"10.1177/26330040241264101","DOIUrl":"https://doi.org/10.1177/26330040241264101","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/26330040241238936.].</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241264101"},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433498","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}

{"title":"STXBP1: fast-forward to a brighter future - a patient organization perspective.","authors":"James R Goss, Benjamin Prosser, Ingo Helbig, Charlene Son Rigby","doi":"10.1177/26330040241257221","DOIUrl":"10.1177/26330040241257221","url":null,"abstract":"<p><p>Syntaxin-binding protein 1 related disorder (STXBP1-RD) is a rare neurologic disorder associated with global neurodevelopmental delay, intellectual disability, early-onset epilepsy, motor abnormalities, and autism. The underlying pathophysiology stems from a <i>de novo</i> mutation in the <i>STXBP1</i> gene, which codes for the STXBP1 protein. The STXBP1 protein is involved in synaptic vesicle fusion and neurotransmitter release. Pathogenic variants in the <i>STXBP1</i> gene generally result in haploinsufficiency, an impairment in neurotransmitter release, and subsequent dysfunction in neuronal communication. The STXBP1 Foundation was founded in 2017 to support families of children with STXBP1-RD and accelerate the development of effective therapies and, ultimately, a cure for the disorder. The Foundation initially supported research aimed at better understanding the complex phenotypic presentation of the disease as well as the development of animal and cellular models usable by the research community to more fully characterize STXBP1 function and disease pathogenicity. In 2023, the Foundation embarked on its STXBP1 Fast Forward Strategic Plan, which includes a prospective natural history study and substantive biomarker work to drive forward the development of new precision therapies for STXBP1-RD.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241257221"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428467","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}

{"title":"Epilepsy and overgrowth-intellectual disability syndromes: a patient organization perspective on collaborating to accelerate pathways to treatment.","authors":"Kerry Grens, Kit M Church, Eric Diehl, Senyene E Hunter, Katrina Tatton-Brown, Jill Kiernan, Christal G Delagrammatikas","doi":"10.1177/26330040241254123","DOIUrl":"10.1177/26330040241254123","url":null,"abstract":"<p><p>Overgrowth-intellectual disability (OGID) syndromes are a collection of rare genetic disorders with overlapping clinical profiles. In addition to the cardinal features of general overgrowth (height and/or head circumference at least two standard deviations above the mean) and some degree of intellectual disability, the OGID syndromes are often associated with neurological anomalies including seizures. In an effort to advance research in directions that will generate meaningful treatments for people with OGID syndromes, a new collaborative partnership called the Overgrowth Syndromes Alliance (OSA) formed in 2023. By taking a phenotype-first approach, OSA aims to unite research and patient communities traditionally siloed by genetic disorder. OSA has galvanized OGID patient organizations around shared interests and developed a research roadmap to identify and address our community's greatest unmet needs. Here, we describe the literature regarding seizures among those with overgrowth syndromes and present the OSA Research Roadmap. This patient-driven guide outlines the milestones essential to reaching the outcome of effective treatments for OGID syndromes and offers resources for reaching those milestones.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241254123"},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201404","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}

{"title":"Linking Angelman and dup15q data for expanded research (LADDER) database: a model for advancing research, clinical guidance, and therapeutic development for rare conditions.","authors":"Sarah Nelson Potter, Elizabeth Reynolds, Katherine C Okoniewski, Anne Edwards, Julia Gable, Christine Hill, Vesselina Bakalov, Stephanie Zentz, Carolyne Whiting, Emily Cheves, Katie Garbarini, Elizabeth Jalazo, Carrie Howell, Amanda Moore, Anne Wheeler","doi":"10.1177/26330040241254122","DOIUrl":"10.1177/26330040241254122","url":null,"abstract":"<p><p>Angelman syndrome (AS) and duplication 15q (dup15q) syndrome are rare neurogenetic conditions arising from a common locus on the long arm of chromosome 15. Individuals with both conditions share some clinical features (e.g. intellectual disability, epilepsy) and often require lifelong care. Disease-modifying therapies for both conditions are emerging, resulting in a significant need for a better understanding of the natural history of both AS and dup15q. Patient advocacy groups for both conditions recognized a need for a data repository that would link data on individuals from multiple sources to expand research, increase understanding of natural history, and accelerate the development of treatments, resulting in the Linking Angelman and Dup15q Data for Expanded Research (LADDER) Database. This paper describes the development and functionality of the LADDER Database - including challenges, lessons learned, and preliminary feasibility - and how it can be used as a model for other rare conditions.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241254122"},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162431","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}

{"title":"Five cases of pulmonary <i>Aspergillus</i> nodules diagnosed at surgery and by pathology in immunocompetent patients, with a literature review.","authors":"Shuangxia Dong, Fengxiang Wang, Haizhen Jin, Xinjian Dai","doi":"10.1177/26330040241252446","DOIUrl":"10.1177/26330040241252446","url":null,"abstract":"<p><p>A pulmonary <i>Aspergillus</i> nodule is a rare subtype of chronic pulmonary aspergillosis. The diagnosis is difficult and is histological. There are only a few reports on such cases. Here, we report five cases of pulmonary <i>Aspergillus</i> nodules confirmed by surgery and pathology in immunocompetent patient and review the literature. Among the five patients in this group, three were females and two were males, aged 44-73 years old. Two cases had hemoptysis onset, and three cases were found to have a slow disease course on chest CT during imaging, ranging from months to years. The white blood cell count, carcinoembryonic antigen, and blood Galactomannan (GM) tests in five cases were all within normal range. Four cases had normal blood C-reactive protein, and one case had an increase. On imaging, there were two cases in the upper lobe of the right lung, two cases in the lower lobe of the left lung, one case in the upper lobe of the left lung, three cases were solitary nodular shadows, and two cases were nodular shadows with cavity formation, including one case with calcification, four cases with bronchial dilation shadows, and one case with gas containing cavity shadows. Five cases were treated with surgical resection and confirmed by histopathological examination. All five patients did not receive antifungal treatment after surgery, and there was no recurrence of Aspergillus nodules during regular follow-up.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241252446"},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162349","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}

{"title":"Corrigendum to \"The Rare Diseases Clinical Research Network: a model for clinical trial readiness\".","authors":"","doi":"10.1177/26330040241256262","DOIUrl":"https://doi.org/10.1177/26330040241256262","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/26330040231219272.].</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241256262"},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11119319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155898","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}

{"title":"Understanding dentatorubral-pallidoluysian atrophy (DRPLA) symptoms and impacts on daily life: a qualitative interview study with patients and caregivers.","authors":"Marielle G Contesse, Rebecca J Woods, Mindy Leffler, Silvia Prades, Julie Greenfield, Andrea Compton, Jeffrey B Carroll","doi":"10.1177/26330040241252447","DOIUrl":"10.1177/26330040241252447","url":null,"abstract":"<p><strong>Background: </strong>Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, neurodegenerative disorder with no disease-modifying treatments. There is a dearth of information in the literature about the patient and caregiver experience living with DRPLA.</p><p><strong>Objectives: </strong>This study aimed to (1) understand symptoms experienced by adult- and juvenile-onset DRPLA populations and their impact on daily life and (2) explore patient and caregiver treatment goals and clinical trial participation preferences.</p><p><strong>Design: </strong>The study was a qualitative interview study.</p><p><strong>Methods: </strong>Interviews were conducted remotely with adult patients with DRPLA and caregivers. Participants described patient symptoms and the impact of those symptoms on daily life, and they discussed treatment goals and potential clinical trial participation. There were 18 patients described in the interviews with two patients and seven caregivers. Some participants were caregivers to multiple patients with DRPLA.</p><p><strong>Results: </strong>Interview transcripts were coded for themes, and reported symptoms were summarized with descriptive statistics. Adult-onset patients (<i>N</i> = 7) experienced difficulty with ataxia (100%), cognition (100%), fine motor skills (100%), gross motor skills (100%), speech (100%), personality changes (100%), and seizures (57%). Juvenile-onset patients (<i>N</i> = 11) experienced difficulty with ataxia (100%), sleep (100%), speech (100%), jerking/twitching (83%), behavior (82%), cognition (82%), fine motor skills (82%), gross motor skills (82%), sensory sensitivity (75%), and seizures (64%). When considering aspects of DRPLA to target for future treatment, patients prioritized ataxia/mobility (100%), juvenile-onset caregivers prioritized ataxia/mobility (60%) and independence (60%), and adult-onset caregivers prioritized personality (60%). Almost all patients (93%) would participate in a clinical trial if given the opportunity, but travel to a clinical site could pose a participation barrier for half.</p><p><strong>Conclusion: </strong>This study found that there are symptom domains that are relevant across the DRPLA population, but there is heterogeneity within each domain based on the age of symptom onset and disease stage, which has implications for clinical trial design.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241252447"},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080380","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}

{"title":"Understanding patient, caregiver, and healthcare provider perspectives of the management of long-chain fatty acid oxidation disorders.","authors":"Eileen Sullivan Baker, Jennifer Botham, Tasia Rechisky, Evelyn Romano, Daniel Garcia, Susan A Berry","doi":"10.1177/26330040241252448","DOIUrl":"10.1177/26330040241252448","url":null,"abstract":"<p><p>Long-chain fatty acid oxidation disorders (LC-FAODs) are a group of rare, inherited, metabolic disorders that can lead to a wide range of symptoms that predominantly affect organ systems with high energy needs, such as the heart, liver, skeletal muscle, and nervous system. Clinical management primarily consists of close attention to and monitoring of diet and activity and avoidance of prolonged fasting. In addition, patients and caregivers must be alert for signs of life-threatening metabolic decompensation. As a result, LC-FAODs can have significant and wide-ranging impacts on the lives of patients and their caregivers. This article describes the effects of LC-FAODs at different life stages and in the context of the North American healthcare system from the perspective of a group of patients, caregivers, and healthcare providers (<i>n</i> = 6). We explain how challenges and needs change throughout life. Following an early diagnosis, an adjustment phase occurs during which caregivers may feel overwhelmed by their new roles and deeply concerned for their children's futures. As children grow, they become more aware of the differences between themselves and their peers, and with increasing independence comes more responsibility for managing their own condition. Major life events, such as new employment and moving house, pose challenges for people of all ages. In addition, it may be difficult to find and connect with qualified and experienced healthcare providers; navigate the health insurance system; and educate and align primary, specialist, and emergency care providers. We propose several strategies to improve the care of patients with LC-FAODs, such as educating local healthcare teams, improving trust between patients/caregivers and healthcare providers, and raising awareness of the challenges faced by patients and caregivers across the different life stages.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241252448"},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080486","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}