Therapeutic advances in rare disease最新文献

{"title":"Koolen-de Vries Syndrome: a journey from diagnosis to treatments.","authors":"Anna C Pfalzer, Blake Ivers, Alayna Haynam, Barbara Drake, David A Koolen, Nael Nadif Kasri, Bert B A de Vries, Heather C Mefford, Angela Morgan, Terry Jo Bichell, Elijah Simon, Ananya Terala, Kenneth A Myers, Ashley Point","doi":"10.1177/26330040241265414","DOIUrl":"10.1177/26330040241265414","url":null,"abstract":"<p><p>The Koolen-de Vries Syndrome Foundation was founded in 2013 with the mission to educate, increase awareness, promote research and develop treatments for individuals living with Koolen-de Vries Syndrome (KdVS) and their families. With this aim, the foundation has focused on: developing scientific resources through patient cell and animal models, providing seed funding to basic and clinical researchers, establishing a natural history study of KdVS and increasing patient engagement. Projects have been prioritized across these areas of focus with an emphasis on expanding international research on KdVS, supporting translational research, establishing an international natural history study and conducting studies to assess patient priorities. With the incredible growth amongst our research and patient community in the last decade, our goal is to have our first clinical trial for KdVS in 2026.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241265414"},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857335","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":"The role of the TSC Alliance in advancing therapy development: a patient organization perspective.","authors":"Steven L Roberds, Zoë Fuchs, Elizabeth M Cassidy, Samantha Metzger, Ayat Abi, Ashley J Pounders, Dean J Aguiar","doi":"10.1177/26330040241265411","DOIUrl":"10.1177/26330040241265411","url":null,"abstract":"<p><p>Tuberous sclerosis complex (TSC) is a genetic disease leading to malformations, or tubers, in the cerebral cortex and growth of tumors, most frequently in the brain, heart, kidneys, skin, and lungs. Changes in the brain caused by TSC usually have the biggest negative impact on quality of life. Approximately 85% of individuals with TSC have epilepsy, and TSC-associated neuropsychiatric disorders (TAND) affect nearly all individuals with TSC in some way. TSC Alliance's research strategy is built upon both funding and catalyzing research. Through grants, the organization provides funding directly to researchers through a competitive application process. The organization has also built a set of resources available to researchers worldwide, including a Natural History Database, Biosample Repository, and Preclinical Consortium. These resources catalyze research because they are available to qualified academic or industry researchers around the world, enabling an almost unlimited number of scientists to access data and resources to enable and accelerate research on TSC. This research strategy continues to be shaped by the needs and priorities of the TSC community, working toward a future where everyone affected by TSC can live their fullest lives.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241265411"},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11273576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790237","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 organization perspective: a research roadmap for Okur-Chung Neurodevelopmental Syndrome.","authors":"Gabrielle V Rushing, Jennifer Sills","doi":"10.1177/26330040241249763","DOIUrl":"10.1177/26330040241249763","url":null,"abstract":"<p><p>Okur-Chung neurodevelopmental syndrome (OCNDS) is an ultra-rare disorder caused by variants in the <i>CSNK2A1</i> gene. <i>CSNK2A1</i> encodes for the alpha subunit of casein kinase 2 (CK2), a serine/threonine kinase critical in neural development. CK2 is implicated in many human pathologies, including viral infections, cancer, inflammation, cardiovascular, neurodegenerative, and psychiatric diseases. However, the mechanism of action for the <i>CSNK2A1</i> variants observed in OCNDS is not fully understood, although studies suggest a loss of function or altered substrate specificity. There are no approved treatments for OCNDS, and current treatments focus on symptom management. The CSNK2A1 Foundation was established in 2018 and aims to find a cure for OCNDS and provide support to affected individuals. OCNDS presents with symptoms at varying severity, including developmental delay/intellectual disabilities, autism, disrupted sleep, speech delays/inability to speak, short stature, and, in ~25% of cases, epilepsy. The foundation has developed a research toolbox that is readily available to researchers worldwide and has awarded ~$1 million in grant funding. These efforts have provided valuable insights into CK2 biology and the natural history of OCNDS. However, additional efforts are needed to fully characterize the disease mechanism and investigate potential treatment interventions. Continued investigation into CK2 and its role in neural development holds promise for a better understanding of OCNDS and related disorders in the future. To accelerate research, we have developed a research roadmap highlighting key focus areas of landscape analysis/toolbox expansion, biomarker development, and therapeutic testing through a series of steps that are nonlinear; we expect these efforts to guide decision-making for therapeutic exploration whether that be drug repurposing, gene therapy, novel drug discovery, or a combination. In this perspective article, we describe OCNDS and the <i>CSNK2A1</i> gene, highlight gaps in OCNDS research, discuss the research roadmap, and offer the founder's perspective on our growth and future opportunities.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241249763"},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11273705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790236","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":"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}