Therapeutic advances in rare disease最新文献

{"title":"Lysosomal storage diseases in North America: a comprehensive review of enzyme therapies and unmet needs.","authors":"Lunawati L Bennett","doi":"10.1177/26330040251405830","DOIUrl":"10.1177/26330040251405830","url":null,"abstract":"<p><p>This review explores enzyme replacement therapies (ERTs) for lysosomal storage diseases (LSDs), focusing on disease characteristics, mechanisms of action, clinical benefits, limitations, and implications for patient care and access. LSDs are a group of over 50 rare, inherited metabolic disorders caused by mutations affecting lysosomal enzymes, membrane proteins, or transporters. This leads to the accumulation of undegraded macromolecules in tissues such as the CNS (central nervous system), heart, and muscles, resulting in progressive dysfunction and possible death. ERTs, approved by FDA (U.S. Food and Drug Administration) and the EMA (European Medicines Agency), have been the cornerstone of treatment since 1995, significantly improving the patient's quality of life reducing organ damage and stabilizing cardiac and renal function. However, ERTs require lifelong intravenous infusions and have limited efficacy to treat CNS symptoms due to their inability to cross the BBB (blood-brain barrier). Some patients develop immune responses known as ADA (anti-drug antibody), which can compromise treatment effectiveness. Emerging research into nanotechnology and combination therapies may help overcome these limitations. Newer formulations such as pegunigalsidase (Elfabrio®) use for FD (Fabry disease), exhibit lower affinity for developing ADA compared to other ERTs, offer reduced immunogenicity and safety profiles enhancement. Cost remains a major barrier, with annual treatment expenses often exceeding hundreds of thousands of dollars. Access to ERT is uneven, particularly in underfunded healthcare systems. In North America, reimbursement varies by region and payer, potentially delaying treatment and impacting outcomes. This review draws from MEDLINE, Cochrane Reviews, and PubMed (1984-2025) using search terms such as LSDs, ERTs, rare diseases, Gaucher disease, Fabry disease, and others. Ongoing research and health policy reforms are essential to improve access, equity, and therapeutic outcomes for patients with LSDs.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251405830"},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12743805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145859111","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":"Clinical characteristics, treatments, and complications of Kawasaki disease in Peruvian children: a retrospective observational study.","authors":"Noé Atamari-Anahui, Giancarlo Alvarado-Gamarra, Nadin Conto-Palomino, Stephanie Cabello-Coca, Jessica La Torre Torreblanca, Danny Asparrin Ramos, María Fernanda Rosado Rullier, Olguita Del Aguila, Jorge Candela-Herrera","doi":"10.1177/26330040251404520","DOIUrl":"10.1177/26330040251404520","url":null,"abstract":"<p><strong>Background: </strong>Kawasaki disease (KD) is a rare medium-sized vessel vasculitis that is the leading cause of acquired heart disease in children. However, most studies on KD focused on its occurrence in infants aged <6 months.</p><p><strong>Objectives: </strong>To evaluate the clinical characteristics, treatments, and complications of KD in Peruvian children.</p><p><strong>Design: </strong>Retrospective observational study.</p><p><strong>Methods: </strong>We collected data from patients aged <18 years who were diagnosed with KD and hospitalized at four healthcare institutions in Lima, Peru, between 2010 and 2022. Clinical characteristics, treatments, and complications were described overall and by age (groups A: <6 months, B: 6 to <12 months, C: 1 to <5 years, and D: ⩾5 years).</p><p><strong>Results: </strong>The median age was 2.3 years (interquartile range: 1.4-4, range: 1 month-13.2 years), and 68% were male. Group A had fewer oral mucocutaneous symptoms, whereas groups C and D had higher frequencies of cervical lymphadenopathy than the other groups. Gastrointestinal symptoms and incomplete KD presentation were common in groups A and D. Elevated white blood cell counts, platelet counts, erythrocyte sedimentation rates, and C-reactive protein levels were observed, particularly in patients with an illness duration of >10 days. A second dose of immunoglobulin was administered to 32 patients, and corticosteroids were administered to 48 patients (21.3%). Immunoglobulin resistance occurred in 14.8% of the patients, predominantly in group D. Coronary aneurysms were observed in 25 patients (12.1%), predominantly in group A. Two patients required intensive care unit admission, and no deaths occurred during hospitalization.</p><p><strong>Conclusion: </strong>Mucocutaneous manifestations of KD in Peruvian children are consistent with those reported in other populations. The frequency of aneurysms and immunoglobulin resistance differed according to age. We emphasize the importance of understanding the clinical presentation of KD, both overall and stratified by age, to prevent late diagnosis and ensure timely treatment.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251404520"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806220","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":"Individualized therapy development for rare diseases: individualized at every step of the way.","authors":"Marlen C Lauffer, Tim Yu, Annemieke Aarstma-Rus","doi":"10.1177/26330040251386869","DOIUrl":"10.1177/26330040251386869","url":null,"abstract":"","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251386869"},"PeriodicalIF":0.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12547107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380221","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":"Gene therapy for children with X-linked myotubular myopathy: a plain language summary of publication for the ASPIRO study.","authors":"Perry B Shieh, Wendy Hughes, Marie Wood, Alan H Beggs, Michael W Lawlor, Julie Coats, Fatbardha Varfaj, Robert J Graham, Nancy L Kuntz, James J Dowling, Wolfgang Müller-Felber, Carsten G Bönnemann, Ana Buj Bello, Laurent Servais, Vicky MacBean, Francesco Muntoni, A Reghan Foley, Astrid Blaschek, Emma S James, Andreea Seferian, Lindsay N Alfano, Tina Duong, Mojtaba Noursalehi, Weston Miller, Jun Lee, Suyash Prasad, Salvador Rico","doi":"10.1177/26330040251362885","DOIUrl":"https://doi.org/10.1177/26330040251362885","url":null,"abstract":"<p><p>What is this summary about? This summary describes the results of a research study (clinical trial) called ASPIRO that was published in the <i>Lancet Neurology</i> in 2023. This study looked at an investigational gene therapy called <b>resamirigene bilparvovec</b> (also known as AT132) as a possible treatment for children with a disease called X-linked <b>myotubular myopathy</b> (abbreviated as XLMTM).</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251362885"},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115427","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":"Systemic inflammation in Fabry disease: a longitudinal immuno-genetic analysis based on variant stratification.","authors":"Haylen Marín Gómez, Miguel López-Garrido","doi":"10.1177/26330040251375498","DOIUrl":"10.1177/26330040251375498","url":null,"abstract":"<p><strong>Background: </strong>Fabry disease is a multisystemic lysosomal disorder caused by mutations in the GLA gene. Although traditionally attributed to lysosomal accumulation of globotriaosylceramide (Gb3), recent evidence suggests a key role of sustained systemic inflammation in its pathogenesis, even in early stages.</p><p><strong>Objectives: </strong>To characterize inflammatory and immunological profiles in a genetically stratified familial cohort with Fabry disease and explore genotype-dependent immune activation patterns.</p><p><strong>Design: </strong>Retrospective, longitudinal study of 11 patients from three interconnected families carrying distinct pathogenic GLA variants.</p><p><strong>Methods: </strong>We analyzed longitudinal data on inflammatory biomarkers (C-reactive protein, ferritin, fibrinogen) and immunological markers (IgG, IgM, IgE, complement C3/C4, anti-enzyme replacement therapy antibodies), alongside clinical variables. Multivariate correlation and unsupervised clustering techniques explored immunophenotypic patterns.</p><p><strong>Results: </strong>All patients exhibited chronic inflammation regardless of genotype. The c.53dup variant showed prominent humoral activation, IVS4+1G>A had complement-mediated activation with a cardiorenal phenotype, and c.845C>T showed mild persistent inflammation. Correlations included CRP and IgG, and complement factors with fibrinogen in the splicing variant group.</p><p><strong>Conclusion: </strong>Inflammation in Fabry disease is not merely a consequence of substrate accumulation but an active and early driver of disease. Preliminary inflammatory phenotypes based on immune mechanisms may guide future personalized therapeutic strategies.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251375498"},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066862","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":"Addressing rare diseases and access to surgical care in Brazil: a call to action.","authors":"Ayla Gerk, Letícia Nunes Campos, Luiza Telles, Sarah Lopes Salomão, Ana Woo Sook Kim, Beatriz Laus Pereira Lima, Sofia Wagemaker Viana, Melissa Zattoni Antonelli, Michelle Brandão, Igor Cunha, Natalia Jereissati, Cristiano Tonello, John G Meara, Nivaldo Alonso","doi":"10.1177/26330040251369887","DOIUrl":"10.1177/26330040251369887","url":null,"abstract":"","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251369887"},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981978","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":"Updated demographics categories to capture the true diversity of an international registry of rare disease patients.","authors":"Nicole Kressin, Michael E Shy, Tara Jones, Nidia Villalpando, Gita Ramdharry","doi":"10.1177/26330040251359676","DOIUrl":"10.1177/26330040251359676","url":null,"abstract":"<p><strong>Background: </strong>NIH requires NIH-funded studies to use historical race and ethnicity categories-originally put forth by the Office of Management and Budget in 1997-for demographics collection. These historical categories were only designed for use within the United States (US). We speculated on the adequacy of these categories in capturing the true diversity of participants enrolled in the Inherited Neuropathy Consortium (INC), and their applicability for an international, broader rare disease population.</p><p><strong>Objectives: </strong>To determine the feasibility and outcomes of using updated categories for rare disease patients that can be collapsed into the required historical categories.</p><p><strong>Design: </strong>This was achieved by expanding on existing government categories from countries with INC sites to create categories that reached 100% consensus of the research team. Quantitative cross-sectional analysis was performed in two cohorts.</p><p><strong>Methods: </strong>Common government census categories among the US, the United Kingdom, Italy, and Australia were used to generate updated demographic categories capturing racial, ethnic, sex, and gender identities. We piloted the updated categories at three INC sites with participants who were participating in the INC. We made a minor update and sent the survey to anyone who had joined the Rare Disease Clinical Research Network's contact registry.</p><p><strong>Results: </strong>Both the pilot study and the contact registry saw an increase in diversity with the updated categories. The sex breakdown of the survey respondents was similar to that of the contact registry as a whole, but several participants were able to identify as nonbinary with the updated categories.</p><p><strong>Discussion: </strong>The updated categories allow researchers to provide a more inclusive race and ethnicity identification experience to participants. This may have implications for understanding differences in study populations that may translate to treatment response and has an overall aim to increase enrollment and adherence to observational research.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251359676"},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777213","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":"Sparsentan in IgA nephropathy: a plain language summary of publication for the PROTECT study.","authors":"Brad H Rovin, Radko Komers, Chris Scroggins, Jonathan Barratt","doi":"10.1177/26330040251355613","DOIUrl":"https://doi.org/10.1177/26330040251355613","url":null,"abstract":"<p><p>What is this summary about? <b>Sparsentan</b> (FILSPARI^®) is a once-daily pill for people with <b>Immunoglobulin</b> A (IgA) <b>nephropathy</b> who are at high risk for worsening kidney disease. Early results from a research study (clinical trial) called PROTECT showed that after 9 months of treatment, <b>sparsentan</b> lowered <b>proteinuria</b> more than <b>irbesartan</b>, a blood pressure medication commonly used to treat IgA <b>nephropathy</b>. These results contributed to <b>sparsentan</b> receiving approval in the United States, the European Union, Switzerland, and the United Kingdom in 2024. This is a plain language summary of publication of an original article published in <i>The Lancet</i> (a medical journal) in November 2023, which reported further results from the PROTECT study. The original article reported on how well <b>sparsentan</b> worked to lower <b>proteinuria</b> and slow the worsening of kidney function (measured by estimated glomerular filtration rate (eGFR)) in people with IgA <b>nephropathy</b> compared with the highest possible dose of <b>irbesartan</b> over an approximately 2-year treatment period. The article also described the side effects that people enrolled in this study had with either <b>sparsentan</b> or <b>irbesartan</b>.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251355613"},"PeriodicalIF":0.0,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683751","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":"Finding buried genetic test results in the electronic health record is inefficient and variable across institutions.","authors":"Olivia J Veatch, Jomol Mathew, Shira Rockowitz, Dustin Baldridge, Alyssa Wetzel, Maria Niarchou, Megan Clarke, Prabhu Shankar, Suma Shankar, Julie S Cohen, Kendell German, Seth Berger, Angela Sellitto, Inez Y Oh, Rashi Raizada, Piotr Sliz, Selvin Soby, Mihailo Kaplarevic, Dan Doherty, Andrea Gropman, Constance Smith-Hicks, Jeffrey L Neul, Virginia Lanzotti, Benjamin Darbro, Qiang Chang, Mustafa Sahin, Maya Chopra","doi":"10.1177/26330040251356521","DOIUrl":"10.1177/26330040251356521","url":null,"abstract":"<p><strong>Background: </strong>The absence of standardized approaches for handling genetic test results in electronic health records (EHRs), combined with a lack of diagnostic codes for most rare disorders, hinders accurate and timely identification of patients with rare genetic variants. This impedes access to research opportunities and genomic-driven care. To reduce the diagnostic odyssey, identify research-eligible subjects, and ultimately enhance patient care, it is critical to optimize approaches to retrieve genetic results.</p><p><strong>Objectives: </strong>To characterize resource requirements, yield, and biases among methods for identifying and retrieving genetic test results across 11 Intellectual and Developmental Disability Research Centers (IDDRC).</p><p><strong>Design: </strong>A survey was used to collect details from the authors on approaches to identify EHRs from patients who had genetic testing and variants of interest were reported; surveys were completed in 2022.</p><p><strong>Methods: </strong>Strengths and limitations in approaches to identify and retrieve genetic test results conducted from the implementation of EHR systems were evaluated. A standard template was used to collect genetic testing storage formats, methods to identify patients with rare disease variants, estimates of time/cost, nature of accessed data, method-specific bias in types of American College of Medical Genetics and Genomics classified variants identified. When possible, precision when performing gene name searches in the EHR was calculated.</p><p><strong>Results: </strong>Four approaches were used: (1) manual searches, reviews, and extractions, (2) natural language processing software-aided manual reviews and extractions, (3) custom databases via testing lab collaborations, and (4) testing EHR vendor-designed genomics modules. The fully manual approach required minimal infrastructure and allowed access to clinical notes but missed variants of unknown clinical significance. Precision for gene name matches based on searches of 59 genes was 0.16. Natural language processing software minimized effort but required considerable informatics support. Custom databases and EHR vendor modules necessitated substantial computational support; however, genetic testing results retrieval was efficient.</p><p><strong>Conclusion: </strong>Leveraging the IDDRC network, we found that methods to store, search and extract genetic testing results vary widely, especially regarding older test results, and have distinct benefits and limitations. Limitations are best addressed through practice guidelines that standardize storage and retrieval of genetic test results to facilitate efficient identification of research eligible subjects and genomic-informed patient care.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251356521"},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628022","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":"Enhancing and leveraging principal investigator and patient advocacy group collaboration in rare disease clinical research-meeting report from the rare Diseases Clinical Research Network.","authors":"Kristen Wheeden, Sheridan Meyers, Kristin Anthony, Mirna Chehade, Rogerwene C Gifford, Eileen C King, Michael Seid","doi":"10.1177/26330040251357318","DOIUrl":"10.1177/26330040251357318","url":null,"abstract":"<p><p>The Rare Diseases Clinical Research Network (RDCRN) works toward faster diagnosis and better treatment for people living with rare diseases, specifically by advancing clinical trial readiness. Inclusion of patient advocacy groups (PAGs) is mandated for each RDCRN consortia; principal investigator (PI)-PAG collaboration is expected to accelerate clinical trial readiness. Real-world examples of PI-PAG collaboration in rare disease clinical research (RDCR) are often not documented nor shared. We report on the Spring 2023 RDCRN meeting, which was dedicated to (a) capturing examples of ways that PAGs and PIs in the RDCRN collaborate, and (b) describing challenges and potential best practices for PAG-PI collaboration. PI and PAG attendees included 50 investigators and staff from 19 consortia and 41 PAG members from 21 consortia. Examples of collaboration in Study Design, Planning and Execution, Funding, and Stakeholder Engagement were captured, as were best practices and challenges to PI-PAG collaboration. Strengthening PI-PAG collaboration can accelerate rare disease research. Documenting real-world examples, and barriers and facilitators of collaboration, from across the RDCRN, supports existing frameworks for accelerating clinical trial readiness.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251357318"},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144628021","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}