Therapeutic advances in rare disease最新文献

{"title":"Frequent report of vitamin deficiencies and use of supplements and complementary/alternative treatment approaches in patients with eosinophilic gastrointestinal diseases.","authors":"Brenderia A Cameron, Elizabeth T Jensen, Xiangfeng Dai, Chelsea Anderson, Ellyn Kodroff, Mary Jo Strobel, Amy Zicarelli, Sarah Gray, Amanda Cordell, Girish Hiremath, Evan S Dellon","doi":"10.1177/26330040251326928","DOIUrl":"https://doi.org/10.1177/26330040251326928","url":null,"abstract":"<p><strong>Background: </strong>Eosinophilic gastrointestinal diseases (EGIDs) impact nutrition.</p><p><strong>Objectives: </strong>To assess the frequency of vitamin deficiencies, supplement use, and complementary/alternative-medication (CAM) use in EoE and non-EoE EGID patients.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>We surveyed members of EGID Partners (egidpartners.org), a patient-centered research network, to assess physician-diagnosed vitamin deficiencies, supplement use, and use of CAM in patients with EoE versus non-EoE EGIDs.</p><p><strong>Results: </strong>Of 81 EGID patients (58 EoE and 23 non-EoE EGID), self-reported frequency of vitamin deficiencies were higher in non-EoE EGIDs compared to EoE (61% vs 50%; <i>p</i> = 0.38; Table 1). Most patients (77%) indicated taking vitamins or supplements, with higher frequency in non-EoE EGID cases (87% vs 72%; <i>p</i> = 0.16). Use of >30 different supplements was reported. For CAM, herbal approaches were more frequent in non-EoE EGIDs compared to EoE (26% vs 5%; <i>p</i> = 0.008).</p><p><strong>Conclusion: </strong>Vitamin deficiencies and supplement/CAM use are frequent in EGIDs, highlighting the need for additional EGID treatment.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251326928"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652427","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 leadership and partnerships accelerate therapies for SCN8A and other developmental and epileptic encephalopathies.","authors":"Gabrielle Conecker, JayEtta Hecker, Michael F Hammer","doi":"10.1177/26330040241252449","DOIUrl":"10.1177/26330040241252449","url":null,"abstract":"<p><p>Families are a driving force in accelerating the understanding and science of SCN8A. The urgency felt by families facing the absence of treatments for their children makes them uniquely positioned to advance therapies through advocacy, data sharing, and partnerships. The International SCN8A Alliance (Alliance) brings families together to collaborate on advancing the science of SCN8A. The Alliance hosts SCN8A <i>scientific meetings -</i> facilitating coordination and collaboration among clinicians, researchers, industry, and the SCN8A community; funds early investigators to <i>support research</i> - building a new generation of investigators; builds and maintains a robust and dedicated International <i>SCN8A Registry</i> (Registry) providing longitudinal data on the natural history of the disorder and leading to over two dozen publications; cultivates <i>partnerships</i> with key stakeholders to accelerate innovation and progress including a Research Consortium, Global Clinicians Network, and the first global Consensus on the Diagnosis and Treatment of SCN8A; coordinates global <i>community engagement</i> by hosting families in virtual meetings in multiple languages and uniting advocates from across all epilepsies to call for more strategic and expanded investment in the epilepsies; builds and hosts the <i>Global SCN8A Leaders Alliance</i> (<i>Leaders Alliance</i>) promoting coordination and collaboration among leaders of SCN8A organizations worldwide; and advances a <i>Global SCN8A Research Roadmap</i> (<i>Research Roadmap</i>) - convening leading stakeholders in the SCN8A community to identify research priorities and accelerate progress toward better care, treatments, and outcomes. The outsized impact of small family advocacy organizations demonstrates that patient advocates can be effective agents in accelerating new therapeutics through maximizing their power to convene diverse stakeholders around a shared vision grounded in patient/caregiver priorities, maintaining a core focus on improving outcomes that are most important to families, and recognizing the importance of being bold, thinking big, and collaborating across disease areas.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040241252449"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484979","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":"Paving the way toward treatment solutions for CTNNB1 syndrome: a patient organization perspective.","authors":"Špela Miroševič, Shivang Khandelwal, Emily Amerson, Effie Parks, Mariana Parks, Lauren Cochran, Ana González Hernández, Mirela Ferraro, Leszek Lisowski, Andrea Perez-Iturralde, Wendy Chung, Michele H Jacob, Nina Žakelj, Duško Lainšček, Vida Forstnerič, Petra Sušjan, Matea Maruna, Roman Jerala, Damjan Osredkar","doi":"10.1177/26330040251318355","DOIUrl":"10.1177/26330040251318355","url":null,"abstract":"<p><p>The CTNNB1 Connect & Cure and CTNNB1 Foundation, alongside Asociación CTNNB1, CTNNB1 Italia, Association CTNNB1 France, and researchers and clinicians globally are dedicated to finding effective treatments and cures for CTNNB1 syndrome. The syndrome is also characterized by progressive spasticity, which can in some cases cause loss of already achieved motor milestones. Since 2019, they have brought together researchers from different fields and invested in various research efforts to advance the search for treatment solutions for patients with CTNNB1 syndrome. Simons Searchlight serves as an important platform by remotely collecting high-quality, standardized data on the natural history of the disease and making it available to researchers around the world. Conducting genotype-phenotype correlation study and biochemically characterizing the mutations were critical to understand the effects of the patients' mutations and related molecular function to symptoms. Several induced pluripotent stem cells were generated from patient cells, and preclinical mouse models have provided new insights into the molecular downstream effects of CTNNB1 haploinsufficiency. Multiple therapeutic approaches are in the developing, including small molecule treatments, RNA- and DNA-based therapies, AAV9 gene replacement therapy, which entered the manufacturing phase in November 2023. In this article, we summarize the journey of the CTNNB1 community and its organizations, highlight ongoing and future research projects, and outline the available research resources. The vision for the CTNNB1 community is that in the future several therapeutic options will be available that can be customized to every CTNNB1 patient's needs.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251318355"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416370","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":"Nirogacestat-the pathway to approval of the first treatment for desmoid tumors, a rare disease.","authors":"Shivaani Kummar, Nam Bui, Wells A Messersmith, Jeanne Whiting, Marlene Portnoy, Allison Lim, L Mary","doi":"10.1177/26330040251317546","DOIUrl":"10.1177/26330040251317546","url":null,"abstract":"<p><p>Drug development for rare diseases can be long, complex, and costly. Desmoid tumors (DT), a rare type of soft-tissue tumor, are associated with substantial and debilitating burden, including disease-specific symptoms (e.g., pain, impaired mobility), reduce functioning for daily activities, and worsen quality of life for patients with this condition. These tumors can be potentially life-threatening when they invade surrounding tissues, affect vital structures, or interfere with the body's functions. Until recently, there were no approved treatments specific to DT and little alignment on disease management. However, on November 27, 2023, the US Food and Drug Administration approved nirogacestat, an oral, targeted, and selective gamma secretase inhibitor, indicated for adult patients with progressing DT who require systemic treatment. This development milestone ascribes to nirogacestat the first approval of a gamma secretase inhibitor for human clinical use and the first therapy specifically indicated for treating patients with DT, thus addressing a long-term unmet need in this patient population. In the DeFi phase III trial of nirogacestat in adults with DT (NCT03785964), nirogacestat demonstrated statistically significant and clinically meaningful improvement in progression-free survival, objective response rate, DT-specific symptom burden (including pain), physical functioning, role functioning, and overall quality of life. This review chronicles the clinical development journey of nirogacestat from 2009 to the present day. Motivated to improve patient outcomes-and navigating considerable skepticism and uncertainty-the dedicated efforts of individuals within academic and medical institutions, industry, and patient advocacy groups shepherded nirogacestat through the development process, including those times when development stalled and might otherwise have been abandoned. Nirogacestat's pathway to becoming a treatment for DT demonstrates how critically important collaboration and coordination are for identifying unique, creative solutions to overcome challenges in rare disease drug development.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251317546"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412057","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":"Behcet's disease in a tertiary eye hospital in Pakistan.","authors":"Tabish Ali Shalwani, Alishan Khowaja, Narmeen Punjwani","doi":"10.1177/26330040251314126","DOIUrl":"10.1177/26330040251314126","url":null,"abstract":"<p><p>Behçet's disease is a kind of variable vessel vasculitis (VVV) and inflammatory systematic disease affecting various organs of the body. The cause of the disease is idiopathic but is most commonly genetic in origin. A positive skin prick test (dermatographia), genital sores, eye irritation, skin sores, and at least three episodes of mouth sores in a year confirm the diagnosis. Treatment may include immunosuppressive agents, immune modulators, and biological markers such as corticosteroids, immunosuppressants, and antibodies. We report a case of a 23-year-old male patient, presented in an outpatient clinic in a tertiary care eye hospital located in Pakistan. The patient reported sudden loss of vision in one eye and graduate loss of vision in the other eye. Ocular and systemic investigations were performed to correlate with clinical findings to reach a diagnosis. The patient was managed symptomatically and was put on corticosteroids. Our hospital is a research and postgraduate educational institution that deals with complex eye diseases. The range of investigations and clinical exams helped clinical decision-makers in evaluating the patient's diagnosis.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251314126"},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017950","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":"Roadmap to advance therapeutics for <i>SYNGAP1</i>-related disorder: a patient organization perspective from SynGAP Research Fund.","authors":"J Michael Graglia, Aaron J Harding, Kathryn A Helde","doi":"10.1177/26330040241308285","DOIUrl":"10.1177/26330040241308285","url":null,"abstract":"<p><p><i>SYNGAP1</i>-related disorder (SRD) is a developmental and epileptic encephalopathy caused by a disruption of the <i>SYNGAP1</i> gene. At the beginning of 2024, it is one of many rare monogenic brain disorders without disease-modifying treatments, but that is changing. This article chronicles the last 5 years, beginning when treatments for SRD were not publicly in development, to the start of 2024 when many SRD-specific treatments are advancing. We discuss the progress across many realms that have brought SRD to the forefront of drug development and highlight how Patient Advocacy Groups (PAGs) have had direct roles in accelerating the route to meaningful treatments for our children. We start with a summary of why SRD is an attractive pharmaceutical target. Second, we introduce the disease, the clinical features, and the number of patients. Next, we describe our PAG, our international partners and cite examples of the broad range of activities we believe are accelerating our pace toward treatments. We summarize the current <i>SYNGAP1</i> pipeline and the status of each public project. Finally, we discuss two open questions that urgently need to be addressed in advance of clinical trials for SRD.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040241308285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980943","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":"Hemophagocytic lymphohistiocytosis as the initial manifestation of bone marrow failure in a child with a TERC variant telomere biology disorder.","authors":"Daniel Medina-Neira, Giancarlo Alvarado-Gamarra, Brenda Huamaní-Condori, Nelson Purizaca-Rosillo, Noé Atamari-Anahui, Erick Matos-Villena, Raquel Garces-Ghilardi, Matilde Estupiñan-Vigil","doi":"10.1177/26330040241311621","DOIUrl":"https://doi.org/10.1177/26330040241311621","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome, rarely associated with bone marrow failure (BMF). Telomere biology disorders (TBD) are caused by inherited defects in telomerase processes and can have heterogeneous presentations including idiopathic pulmonary fibrosis, cirrhosis, and BMF. We report a case of a 10-year-old male from Lima, Peru, who presented with HLH as the initial manifestation of a TBD. He experienced fever, gastrointestinal symptoms, and mucocutaneous involvement. Initial laboratory analyses revealed pancytopenia and elevated inflammatory markers. Despite symptomatic and antibiotic treatment, his clinical condition persisted leading to a suspicion of Kawasaki disease and, subsequently, HLH. Immunomodulatory treatment was initiated with a good clinical response. Bone marrow aspiration revealed severe hypocellular bone marrow and cytophagocytosis. Genetic studies identified a pathogenic variant in the <i>TERC</i> gene (n.110_113del), which was also found in the patient's mother and brother. HLH as the initial manifestation of BMF is rare. This case highlights the importance of considering TBD in children with BMF of unclear etiology and the value of genetic testing in such cases.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040241311621"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960195","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":"WITHDRAWAL - An inborn error of metabolism presenting with apparently isolated subacute neuropsychiatric symptoms in an adolescent.","authors":"","doi":"10.1177/26330040241309151","DOIUrl":"https://doi.org/10.1177/26330040241309151","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1177/26330040241290907.].</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241309151"},"PeriodicalIF":0.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908029","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":"Advancing rare disease measurement through the Rare Disease Clinical Outcome Assessment Consortium.","authors":"Naomi Knoble, Lindsey T Murray","doi":"10.1177/26330040241307962","DOIUrl":"10.1177/26330040241307962","url":null,"abstract":"<p><p>There is a significant unmet need to develop and evaluate new treatments for people living with one of approximately 8000 rare diseases. Well-known difficulties in conducting clinical trials (e.g., small samples, wide geographic distribution, heterogeneous symptoms) and developing products for these rare indications persist. Identifying outcomes in rare disease clinical trials remains a hurdle that contributes to the challenges for drug and gene therapy development due to uncertainty about what aspects of a condition to measure for safety and efficacy and often with no regulatory approval precedent. To accelerate rare disease treatments by advancing outcomes measurement, the US Food and Drug Administration (FDA) funded a cooperative agreement to establish the Rare Disease COA Consortium (RD-COAC) in 2019. The RD-COAC officially launched on January 1, 2022, with the mission to enable pre-competitive, multi-stakeholder collaboration aimed at identifying scientifically sound tools and methodologies for collecting clinically meaningful and patient-centric outcomes data in treatment trials for rare diseases. The RD-COAC has four complementary workstreams to advance COA measurement for rare disease clinical trials: (1) Rare Disease COA Resource; (2) Advancing COA Measurement Topic-Focused Working Groups; (3) Rare Disease Discussion Sessions for pre-competitive collaboration and shared learnings among RD-COAC members; and (4) Dissemination. This review provides an overview of the RD-COAC's activities to date, as well as future directions and opportunities to collaborate.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241307962"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848472","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":"Hutchinson-Gilford progeria syndrome: unraveling the genetic basis, symptoms, and advancements in therapeutic approaches.","authors":"Akhil Arun, Athira Rejith Nath, Bonny Thankachan, M K Unnikrishnan","doi":"10.1177/26330040241305144","DOIUrl":"10.1177/26330040241305144","url":null,"abstract":"<p><p>Hutchinson-Gilford Progeria syndrome (HGPS) serves as a prominent model for Progeroid syndromes, a group of rare genetic disorders characterized by accelerated aging. This review explores the genetic basis, clinical presentation, and complications of HGPS. HGPS is caused by mutations in the LMNA gene, resulting in the production of a defective structural protein, prelamin A. This protein contains a \"CAAX\" motif, where C represents cysteine, and its abnormal processing is central to the disease's pathology. HGPS leads to multiple organ systems being affected, including cardiovascular, skeletal, neurological, and dermatological systems, causing severe disability and increased mortality. Cardiovascular issues are particularly significant in HGPS and are crucial for developing therapeutic strategies. Recent advances in treatment modalities offer promise for managing HGPS. Farnesyltransferase inhibitors and genetic interventions, such as CRISPR-Cas9, have shown potential in mitigating progerin-associated symptoms, with encouraging results observed in preclinical and clinical studies. Additionally, emerging therapies such as rapamycin, sulforaphane, and MG132 hold promise in targeting underlying disease mechanisms. Comprehensive management approaches, including growth hormone therapy, retinoids, and dental care, are emphasized to enhance overall patient well-being. Despite progress, further research is essential to unravel the complex pathophysiology of Progeroid syndromes and develop effective treatments. Continued focus on therapies that address progerin accumulation and its downstream effects is vital for improving patient care and outcomes for individuals affected by HGPS and related disorders. This review highlights ongoing efforts to understand and combat Progeroid syndromes, aiming to alleviate the burdens imposed by these debilitating conditions.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241305144"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848635","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}