Therapeutic advances in rare disease最新文献

{"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}

{"title":"Neuroanatomical anomalies due to a defect in the FGF3 gene, associated with the Labyrinthine Aplasia, Microtia and Microdontia syndrome: insights from the placement of auditory brainstem implants in two siblings.","authors":"Johan H M Frijns, Roos M G S Geerders, Esther Scholing, Berit M Verbist, Radboud W Koot, Martijn J A Malessy, Peter-Paul B M Boermans, Jeroen J Briaire","doi":"10.1177/26330040241290834","DOIUrl":"10.1177/26330040241290834","url":null,"abstract":"<p><p>Here, we describe two congenitally deaf male siblings with the same compound heterozygotic, likely pathogenic mutations in the FGF3 gene, associated with the labyrinthine aplasia, microtia and microdontia (LAMM) syndrome. Both children had bilateral cochleovestibular aplasia, precluding cochlear implantation. The elder brother received an auditory brainstem implant (ABI) with very limited auditory responses. During the ABI-surgery of the younger subject, it was discovered that excellent auditory responses could be obtained when the electrode array was placed considerably more caudally and more medially than standard. It was observed that the foramen of Luschka, the entrance to the lateral recess of the fourth ventricle was located more caudally. In view of this observation the good auditory development of the latter child, it was decided to give the older child a contralateral ABI. Again, it turned out that the anatomy of the brainstem was abnormal with a more caudal location of the foramen of Luschka and the cochlear nucleus, and this child is showing good progress with his auditory development. It is concluded that one should be aware of the anatomical differences at the level of the brainstem when placing an ABI in children with this genetic disorder (and most likely also in the LAMM syndrome). This also underpins the need of a multidisciplinary approach with closely collaborating team members and good family guidance when diagnosing and treating children with rare deafness.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241290834"},"PeriodicalIF":0.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559590","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 roadmap to cure CHD2-related disorders.","authors":"Stephanie Prince, Emily Bonkowski, Christopher McGraw, Christina SanInocencio, Heather C Mefford, Gemma Carvill, Brian Broadbent","doi":"10.1177/26330040241283749","DOIUrl":"10.1177/26330040241283749","url":null,"abstract":"<p><p>Coalition to Cure CHD2 (CCC) is a patient advocacy group dedicated to improving the lives of those affected by CHD2-related disorders (CHD2-RD) by increasing education, building community, and accelerating research to uncover a cure. CHD2 is a chromatin remodeler that was identified in 2013 as being a genetic cause for developmental and epileptic encephalopathies. Pathogenic changes in CHD2 can cause treatment-resistant epilepsy, intellectual and developmental delays, and autism, and some individuals experience neurodevelopmental regression. There are currently no targeted therapies available for CHD2-related disorders. Haploinsufficiency of CHD2 is a causative mechanism of disease for individuals with pathogenic variants (primarily truncating) in CHD2. Recently, identification of individuals with deletion of nearby gene CHASERR, a regulator of CHD2 gene expression, has established dosage sensitivity in CHD2 and solidified the CHASERR gene as a potential therapeutic target for CHD2 levels. Through collaboration with our community and our scientific advisory board, CCC has created a Roadmap to Cure CHD2 as our guide toward a targeted cure that can benefit our community, with steps including (1) identifying and defining patients, (2) developing models of CHD2, (3) studying models of CHD2, (4) testing therapies, (5) involving patients, and (6) reaching a cure. Despite some of the challenges inherent in CHD2 research including establishing animal and cellular models that recapitulate the CHD2 clinical phenotype, identifying measurable outcomes and reliable biomarkers, or testing emerging therapeutic approaches, CCC continues to engage with our community to support ongoing research that aligns with our priorities. CCC sees new and exciting opportunities for additional research that can move our community toward our common goal of a cure that will improve the lives of individuals and their families now and in the future.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241283749"},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402305","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":"Erratum to \"Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials\".","authors":"","doi":"10.1177/26330040241277869","DOIUrl":"https://doi.org/10.1177/26330040241277869","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/26330040241249762.].</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241277869"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395862","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":"<i>SLC6A1</i> patient & organization perspective: founding of SLC6A1 connect, research, and ongoing efforts.","authors":"Jacob Tiller, Melissa B DeLeeuw, Jing-Qiong Kang, Amber Freed","doi":"10.1177/26330040241283734","DOIUrl":"https://doi.org/10.1177/26330040241283734","url":null,"abstract":"<p><p>This paper describes the founding of the SLC6A1 Connect organization, which offers resources to patients and families with <i>SLC6A1</i> diagnoses while keeping current with a scientific overview of the disorder. Following the birth of her two lovely twins, Amber Freed noticed how her son, Maxwell, missed motor development milestones and would often stare. Eventually, these signs led to a diagnosis of an <i>SLC6A1</i> variant. The <i>SLC6A1</i> gene is located on the short arm of chromosome 3 and the gene encodes for the gamma-aminobutyric acid (GABA) transporter 1 (GAT-1) protein. This transporter is responsible for the reuptake of the inhibitory neurotransmitter, GABA. The transporter usually removes GABA from the synapse space between two neurons, limiting over-excitability in the brain, which can lead to seizures and motor deficits as Amber noticed in her son, Maxwell. Amber realized that there were nearly no treatment options for her son's condition so she began forming connections with scientists and doctors. Initially, she flew to see Dr. Steven Gray, with whom she developed a research plan for a gene replacement therapy to treat the variant along with a design for a clinical trial. Not only this but they needed to raise four million dollars to fund these endeavors. Freed founded the <i>SLC6A1</i> Connect organization to raise money and awareness and put together a network of dedicated researchers and families. Since then, the organization has raised over two million dollars and grown to offer families a base of support. The organization even hosts a yearly symposium with families, scientists, and biotech or pharmaceutical companies worldwide. In addition, we detail how the organization now offers informational resources to families to help them understand the science behind the variant and ways to help their children such as registry links and genetic testing options. These endeavors have led the organization to collaborate with scientists based on institutions such as Vanderbilt University Medical Center, UT Southwestern Medical Center, the Cleveland Clinic, and many industrial pharmaceutical partners.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241283734"},"PeriodicalIF":0.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395861","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}