Therapeutic advances in rare disease最新文献

{"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}

{"title":"Joining forces to develop individualized antisense oligonucleotides for patients with brain or eye diseases: the example of the Dutch Center for RNA Therapeutics.","authors":"Annemieke Aartsma-Rus, Rob W J Collin, Ype Elgersma, Marlen C Lauffer, Willeke van Roon-Mom","doi":"10.1177/26330040241273465","DOIUrl":"https://doi.org/10.1177/26330040241273465","url":null,"abstract":"<p><p>Antisense oligonucleotides (ASOs) offer versatile tools to modify the processing and expression levels of gene transcripts. As such, they have a high therapeutic potential for rare genetic diseases, where applicability of each ASO ranges from thousands of patients worldwide to single individuals based on the prevalence of the causative pathogenic variant. It was shown that development of individualized ASOs was feasible within an academic setting, starting with Milasen for the treatment of a patient with CLN7 Batten's disease in the USA. Inspired by this, the Dutch Center for RNA Therapeutics (DCRT) was established by three academic medical centers in the Netherlands with a track record in ASO development for progressive, genetic neurodegenerative, neurodevelopmental, and retinal disorders. The goal of the DCRT is to bundle expertise and address national ethical, regulatory, and financial issues related to ASO treatment, and ultimately to develop individualized ASOs for eligible patients with genetic diseases affecting the central nervous system in an academic, not-for-profit setting. In this perspective, we describe the establishment of the DCRT in 2020 and the achievements so far, with a specific focus on lessons learned: the need for processes and procedures, the need for global collaboration, the need to raise awareness, and the fact that N-of-1 is N-of-a-few.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241273465"},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334028","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: Proceedings from the MENA Congress for Rare Diseases, 16-19 May 2024, Abu Dhabi, UAE.","authors":"","doi":"10.1177/26330040241280488","DOIUrl":"https://doi.org/10.1177/26330040241280488","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1177/26330040241238936.].</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241280488"},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11403550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303026","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 small steps that lead to big impact: translating therapeutics from idea to reality for the CDKL5 deficiency disorder community.","authors":"Amanda Jaksha, Marissa Bishop, Karen Utley, Heidi L Grabenstatter","doi":"10.1177/26330040241275673","DOIUrl":"10.1177/26330040241275673","url":null,"abstract":"<p><p>Despite the unmet needs of patients living with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) and the challenges facing a rare population with small patient numbers, now is a time of unprecedented opportunities to turn scientific breakthroughs into safe and effective treatments for families of CDD patients. New data collected for over a decade and an evolution in genetics technologies have resulted in transformational new treatments currently in development for CDD. This progress is in great part due to the patient advocacy efforts early on to drive development of stakeholder research tools necessary to de-risk industry entry into the CDD space, family participation in longitudinal natural history studies, and a robust caregiver-reported database. Cumulatively, these efforts offered new insights into CDD, specifically patterns in disease progression, helped identify the most burdensome symptoms to patients and caregivers, improved clinical trial design, and reduced financial barriers for therapeutic development for potential industry partners. This paper documents the growth of a small patient community through relationship building and collaboration. The International Foundation for CDKL5 Research is mindful of ongoing challenges namely the long research timelines, high development and production costs, and inequitable access to approved therapies. Therefore, sustaining strong early resources while recognizing opportunities that engagement, advocacy, and funding can accelerate progress remains at the heart of the agile foundation strategy.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"5 ","pages":"26330040241275673"},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156891","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}