Rare Diseases Clinical Research Network (RDCRN)’s Post

#neurodegeneration #alzheimer #metabolism https://lnkd.in/gT2qiVgD #Apolipoprotein E (APOE) encodes a lipid carrier and is an important genetic risk factor for sporadic Alzheimer disease (AD), but the underlying mechanisms have not been fully elucidated. A new study in Neuron reports that in tau models of AD, the APOE4 variant contributes to impaired lipid handling and #neuroinflammation in microglia. Moreover, strategies to increase #lipid efflux from microglial cells can rescue AD-like pathology in tau-mutant mice, highlighting potential therapeutic avenues.

How can we better navigate the diagnosis and treatment of Duchenne muscular dystrophy? Join Dr. Kay Davies as she dives into the causes, progression, and current treatment options for DMD, a challenging genetic disorder. In this insightful discussion, Dr. Davies highlights the importance of early diagnosis and the role of innovative therapies in improving patient outcomes. From the latest advancements in gene therapy to the development of novel treatment strategies, learn how these breakthroughs are shaping the future of DMD care. Check out the full program to enhance your practice today: https://ow.ly/3EKc50SL2f5 #DMD #MedicalResearch #GeneticDisorders #NeuroFrontiers #HealthcareInnovation #GeneTherapy #PatientCare

Recently, I encountered Dr. X., a pediatric neurologist, in the hallway. I mentioned that I now follow G.´s family for their medical genetics appointments. The family asked me to express their profound appreciation to Dr. X for her compassionate care and dedication to G. during his years living with Duchenne muscular dystrophy (DMD). When Dr. X. inquired about G.'s well-being, a lump formed in my throat. I had to share the difficult news that G. had sadly passed away two years ago in his early twenties from complications of DMD. Dr. X.'s eyes welled up, and a heavy silence filled the air. We then shifted gears, discussing the crucial importance of maintaining accurate patient data with genetic information. G. had a nonsense mutation, which may be targeted by future gene therapies. Up-to-date records are essential for matching DMD patients with the most appropriate gene therapy options. In that quiet moment of reflection, Dr. X.'s gaze towards the empty wall wasn't just about grief, but about the future. It was a poignant reminder that while treatments may not have arrived in time for G., our continued efforts hold the promise of a brighter future for other DMD patients. Let's honor G. and the estimated 20,000 children diagnosed with DMD globally every year. Together, we can work towards a future where science offers hope. #DuchenneMuscularDystrophy #GeneTherapy #NeverGiveUp Link: www.worldduchenne.org

Duchenne Muscular Dystrophy, or DMD, is considered a rare disease, but to the patients afflicted, it is a painful, everyday experience. Are you up to date on the latest, most effective approaches to care for DMD? In this educational program, gain insights on the role of multidisciplinary teams in the early diagnosis and ongoing monitoring of DMD. Discover strategies for integrating gene therapy advancements into your practice and learn how to incorporate the unique perspectives of patients and caregivers into clinical decision-making. Elevate care for your patients with DMD today: https://ow.ly/waqF50RzLiK #CME #MedEd #DuchenneMuscularDystrophy #GeneTherapy #ClinicalTrials

Discover a rare case report of a neonate with Gray Platelet Syndrome and VACTERL association. This fascinating case explores the clinical findings and genetic mutations leading to diagnosis. 🔗 Read the full article: https://hubs.la/Q02S8ZKZ0 #CaseReport #GrayPlateletSyndrome #VACTERL #RareDiseases #Neonatology #Thrombocytopenia #GeneticDisorders #PlateletDisorders #CongenitalAnomalies #PediatricSurgery #MedicalGenetics #BirthDefects #CureusJournal #ClinicalResearch #GeneticAnalysis #PatientCare #HealthcareInnovation #MedicalScience #RareConditions #NewbornCare #Cureus #MedEd

Latest discovery! The scientists published their latest discovery titled “PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome” On Cell. They found the immunogenicity of PNMA2 could result in neurological deficits.   The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. The scientists show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external “spike” PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits. The article DOI: 10.1016/j.cell.2024.01.009 In addition, we provide a number of genetically engineered PNMA2-targeted mouse models, some of which are ready to be shipped in as early as two weeks. Contact us at service.us@modelorg.com to learn more.  #mousemodel #neuroscienceresearch #neurologicaldisorders #SMOC

#Alzheimer #apolipoproteinEisoforms #amyloidbeta Impact of apolipoprotein E isoforms on sporadic Alzheimer’s disease: beyond the role of amyloid beta https://lnkd.in/gwYkm4RY Università degli Studi di Bari The impact of apolipoprotein E (ApoE) isoforms on sporadic Alzheimer’s disease has long been studied; however, the influences of apolipoprotein E gene (APOE) on healthy and pathological human brains are not fully understood. The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer’s disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE, brain function, and memory, from a molecular to a clinical level. APOE genotype also exerted a heterogeneous effect on clinical Alzheimer’s disease phenotype and its outcomes. Not only in learning and memory but also in neuropsychiatric symptoms that occur in a premorbid condition. Clarifying the relationships between Alzheimer’s disease-related pathology with neuropsychiatric symptoms, particularly suicidal ideation in Alzheimer’s disease patients, may be useful for elucidating also the underlying pathophysiological process and its prognosis. Also, the effects of anti-amyloid-beta drugs, recently approved for the treatment of Alzheimer’s disease, could be influenced by the APOE genotype.

Five #mutations identified in genes associated with Primary electrical disorders (#PED) and Sudden #cardiac Death (#SCD) may aid in the #clinicaldiagnosis of PED. To read more on impact of #gene #mutations, click here https://lnkd.in/enj2YWPK #CVIA #CVIAJournal #openaccessjournal #geneticresearch #cardiacarrest #cardiomyopathy #cardiology #cardioed #medicalscience ScienceOpen #cardiologists

Cool paper in Developmental Cell: Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts https://lnkd.in/eb65z6Xk Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, highly heterogeneous neurodegenerative disease, underscoring the importance of obtaining information to personalize clinical decisions quickly after diagnosis. Here, we investigated whether ALS-relevant signatures can be detected directly from biopsied patient fibroblasts. We profiled familial ALS (fALS) fibroblasts, representing a range of mutations in the fused in sarcoma (FUS) gene and ages of onset. To differentiate FUS fALS and healthy control fibroblasts, machine-learning classifiers were trained separately on high-content imaging and transcriptional profiles. “Molecular ALS phenotype” scores, derived from these classifiers, captured a spectrum from disease to health. Interestingly, these scores negatively correlated with age of onset, identified several pre-symptomatic individuals and sporadic ALS (sALS) patients with FUS-like fibroblasts, and quantified “movement” of FUS fALS and “FUS-like” sALS toward health upon FUS ASO treatment. Taken together, these findings provide evidence that non-neuronal patient fibroblasts can be used for rapid, personalized assessment in ALS.

🔬✨ Special Issue #CallForPaper: Hormone Receptors in Human Malignancies Hormone receptors, crucial for regulating gene expression, play significant roles in the development and progression of various cancers. While extensively studied in prostate and breast cancers, their impact on other malignancies like lung, gastrointestinal, liver, endometrial, ovarian, and urothelial cancers is less understood. This Special Issue aims to provide an overview of recent findings on hormone receptor signaling in a wide range of cancers. We invite original research and review articles exploring the involvement of any hormone receptor in any human malignancy. Guest Editors: 👨⚕️ Hiroshi Miyamoto, University of Rochester Medical Center,  Professor of Pathology & Laboratory Medicine and Urology, University of Rochester School of Medicine and Dentistry 👨⚕️ Shuyuan Yeh, University of Rochester Medical Center 📖 Read more: https://lnkd.in/d336H5gv #SteroidHormoneReceptors #PeptideHormoneReceptors #Carcinogenesis #CancerProgression #Metastasis #TherapeuticResistance #Prognosis #Transactivation #Transrepression #Coactivators #Corepressors #Agonists #Antagonists #CancerResearch #OncologyResearch #MedicalResearch #HealthScience #HormoneReceptors #TechSciencePress