Therapeutic advances in rare disease最新文献

{"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}

{"title":"Count Me In: patient-partnered research to address disparities for rare cancer patients.","authors":"Priyanka Bhakhri, Kolbe Phelps, Jorge Gómez Tejeda Zañudo, Erin Gwozdz, Sophia Ko, Taisha Hendrickson, Elana Anastasio, Diane M Diehl, Corrie A Painter, Mary McGillicuddy","doi":"10.1177/26330040241304440","DOIUrl":"10.1177/26330040241304440","url":null,"abstract":"<p><strong>Background: </strong>Approximately 25% of cancer patients are diagnosed with rare cancers and face unique challenges. Decentralized patient-partnered research efforts, like Count Me In provide an avenue for patients to participate in research that overcomes key barriers to address disparities in rare cancer research to accelerate discovery.</p><p><strong>Objectives: </strong>Projects in metastatic breast cancer (The Metastatic Breast Cancer Project; MBCproject) and angiosarcoma (The Angiosarcoma Project; ASCproject) highlight disparities that exist for all cancer patients and underscore those that are compounded for rare cancer patients.</p><p><strong>Design: </strong>Through Count Me In's research platform, patients visit a website to enroll in the study and complete surveys, which allows us to access their medical records and biospecimens. Clinically annotated sequencing data are de-identified and released on research platforms.</p><p><strong>Methods: </strong>MBCproject and ASCproject data were analyzed to identify differences between patients with a more common and rare cancer, respectively. The analysis included outreach strategies, patient-reported themes, and distance traveled for care.</p><p><strong>Results: </strong>As of September 28, 2023, 3742 patients have enrolled in MBCproject and 491 patients have enrolled in the ASCproject from across the United States and Canada. Outreach strategies were tailored to resource availability. Using survey information, it was observed that patients with a rare cancer (angiosarcoma) traveled longer distances to receive care than those with a more common cancer (metastatic breast cancer) for three major cancer centers. Patients with rare and common cancers highlighted different themes when asked about their disease experience. Themes like misdiagnosis and discontent with resource availability came up more often for rare cancer patients. Data sharing and collaboration in angiosarcoma research enabled rapid discoveries with clinical impact.</p><p><strong>Conclusion: </strong>Count Me In's platform has led to unprecedented data generation and findings in rare cancer through partnering with patients. Directly engaging with patients to generate and share data while emphasizing collaboration sets the foundation for a more equitable future.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241304440"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848486","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":"Gastrointestinal langerhans cell histiocytosis in an adult presenting with anal protrusion and multiple colorectal ulcers: a case report.","authors":"Nhu Tung Tran, Quoc Thanh Truong, Khuyen Thi Nguyen, The Anh Khoa Lai, Cong Thao Trinh, Van Trung Hoang","doi":"10.1177/26330040241301799","DOIUrl":"https://doi.org/10.1177/26330040241301799","url":null,"abstract":"<p><p>Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the proliferation of Langerhans cells, a type of dendritic cell essential for immune response. While LCH predominantly affects children, its manifestation in adults, especially within the gastrointestinal (GI) tract, is exceedingly rare. We present a unique case of a 56-year-old female with rare GI manifestations of LCH. The patient initially noticed pimple-like lesions around her anal orifice, which evolved into prominent protruding lesions over 3 months. Subsequent colonoscopy revealed multiple ulcers in the colorectal area, particularly concentrated in the sigmoid colon. Histopathological examination of biopsy samples, combined with immunohistochemical staining, confirmed the diagnosis of LCH. This case underscores the importance of a comprehensive diagnostic approach, especially when patients are present with atypical symptoms. The current literature suggests that such GI manifestations of LCH in adults are infrequent, making this case a valuable contribution to the understanding of LCH's clinical spectrum.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241301799"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775262","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 MED13L Foundation strategic research plan: a roadmap to the future.","authors":"Rachel Heilmann, Anna Pfalzer, Terry Jo Bichell, Ananya Terala, Alicia Campbell, Dylan Taatjes, Jamal Ghoumid, Chad Grueter, Jennifer Bain, Randy Strich, Vanessa Dias, Kimberly Sokorai, Nicholas Seaver, Kelly Sexton, Kathleen Boychuck","doi":"10.1177/26330040241290252","DOIUrl":"https://doi.org/10.1177/26330040241290252","url":null,"abstract":"<p><p>A strategic research plan (SRP) serves as a compass for the patient advocacy organizations driving the therapeutic options for their rare disorder. The MED13L Foundation commissioned the SRP in 2022 through COMBINEDBrain, a consortium of patient advocacy organizations of rare neurodevelopmental disorders, working toward clinical trial readiness. The MED13L Foundation SRP is an objective evaluation of MED13L literature including clinical and basic science knowledge interwoven with an assessment of preclinical trial readiness tools necessary for achieving therapeutic interventions. Clinical evaluation is conducted through a review of the literature documenting symptoms and variant information for each individual with MED13L syndrome. Data is collated and presented as a summary, providing any unique genotype-phenotype, as applicable. Scientific literature is reviewed in the same manner, identifying areas of opportunity to expand knowledge of MED13L syndrome. Researchers and clinicians responsible for growing the understanding of MED13L syndrome are interviewed and information is shared to create an open and collaborative network. Preclinical trial readiness tools are largely framed through Food and Drug Administration guidelines for the development of therapeutics from bench to bedside. Finally, the Foundation infrastructure and community engagement are assessed providing areas of strengths and opportunities to elevate the bond formed to drive patient-centered research forward. Completed, this SRP becomes a living resource for the MED13L Foundation to set priorities, share with researchers and clinicians, and provide direction to reach their organizational goals, including therapies for their community affected by MED13L syndrome.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241290252"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775282","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":"An inborn error of metabolism presenting with apparently isolated subacute neuropsychiatric symptoms in an adolescent.","authors":"Sarah Grace Engel, Ali Said Al-Beshri, Amitha Ananth, Salman Rashid","doi":"10.1177/26330040241290907","DOIUrl":"10.1177/26330040241290907","url":null,"abstract":"<p><p>We discuss a previously healthy adolescent male presenting with subacute neuropsychiatric issues, tremors, hyperreflexia, and hypertension. Laboratory studies revealed acute on chronic kidney disease. Additional investigations yielded a treatable late-onset inborn error of metabolism (IEM). Late-onset forms of IEMs may present very differently than early-onset disease manifestations (e.g., neuropsychiatric issues may be the predominant symptom), thus leading to the underrecognition of a treatable underlying etiology.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241290907"},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634521","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":"A patient organization perspective: charting the course to a cure for SCN2A-related disorders.","authors":"Leah F Schust, Jennifer Burke, Christina SanInocencio, Brad A Bryan, Karen S Ho, Shawn M Egan","doi":"10.1177/26330040241292645","DOIUrl":"https://doi.org/10.1177/26330040241292645","url":null,"abstract":"<p><p>The SCN2A gene encodes the Nav1.2 protein, a voltage-gated sodium channel crucial for initiating and transmitting action potentials in neurons. Dysfunction in Nav1.2, often stemming from genetic mutations in the SCN2A gene, leads to SCN2A-related disorders. Individuals harboring pathogenic SCN2A variants present with severe neurodevelopmental disorders such as epilepsy, autism spectrum disorders, movement disorders, cortical visual impairment, and intellectual disabilities. The FamilieSCN2A Foundation, a 501(c)(3) patient advocacy organization, is dedicated to enhancing the lives of those affected by SCN2A-related disorders. Fueled by a vision of a world with effective treatments and cures for all patients with SCN2A-related disorders, FamilieSCN2A Foundation has charted the course to a cure based on their core values of urgency, integrity, collaboration, and inclusion. Their strategic plan centers on building a comprehensive research-readiness infrastructure that maximizes the probability of bringing curative therapies to SCN2A patients. Appreciating that statistically most drug development initiatives will fail, creating an infrastructure that maximizes the number of drugs in development for SCN2A-related disorders in turn maximizes the net probability of success that FamilieSCN2A Foundation will achieving their vision. Through dynamic initiatives and notable achievements, including raising ~$6 million USD, funding 26 research grants totaling ~$4.7 million USD, and forging strategic partnerships across the SCN2A-related disorder ecosystem the foundation is actively executing its strategic plan. With SCN2A research advancing rapidly and a thriving ecosystem of diverse, engaged stakeholders, FamilieSCN2A Foundation believes the outlook for SCN2A-related disorders is bright.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241292645"},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634520","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":"Congenital insensitivity to pain with anhidrosis: a literature review and the advocacy for stem cell therapeutic interventions.","authors":"Muhammad Ikrama, Muhammad Usama, Muhammad Hassan Haider, Shifa Israr, Maryam Humayon","doi":"10.1177/26330040241292378","DOIUrl":"10.1177/26330040241292378","url":null,"abstract":"<p><p>Congenital Insensitivity to Pain with Anhidrosis (CIPA) is a rare genetic disorder affecting the autonomic nervous system, leading to an inability to feel pain, temperature, or sweat1. This condition is caused by mutations in the NTRK1 gene, which encodes a receptor for nerve growth factor (NGF). The lack of NGF signaling results in the improper development and function of sensory and sympathetic neurons. Patients with CIPA often suffer from repeated injuries, infections, and hyperthermia due to their inability to sense pain and regulate body temperature. Management focuses on preventing injuries, controlling infections, and providing supportive care, as there is no definitive cure for CIPA. We present several hypotheses for treating CIPA using stem cells and modern genetic techniques. One approach involves using induced pluripotent stem cells (iPSCs) to replace defective neurons. Another hypothesis suggests in vivo gene editing of neural progenitors to restore TrkA function. Additionally, mesenchymal stem cells (MSCs) genetically modified to overexpress NGF could provide trophic support. Other strategies include epigenetic modulation of NTRK1 expression and exosome-mediated gene therapy. These innovative approaches aim to address the underlying genetic defects and restore normal cellular functions in CIPA patients.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241292378"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570627","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}