Overview of latest articles and publications on gene therapy in PubMed, including Human Gene Therapy, Journal of Molecular Medicine and Journal of Gene Medicine. PubMed is a service of the US National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals.

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• Improving access to gene therapy for rare diseases Fri, 19 Apr 2024 06:00:00 -0400
  Effective gene therapy approaches have been developed for many rare diseases, including inborn errors of immunity and metabolism, haemoglobinopathies and inherited blindness. Despite successful pre-clinical and clinical results, these gene therapies are not widely available, primarily for non-medical reasons. Lack of commercial interest in therapies for ultra-rare diseases, costs of development and complex manufacturing processes required for advanced therapy medicinal products (ATMPs) are some...


• Transcriptome-Based Treatment for Melanoma With Brain Metastasis: A Case Report Fri, 19 Apr 2024 06:00:00 -0400
  Malignant melanoma with brain metastasis has a high mortality rate. New approaches for diagnosis and treatment are urgently required to improve prognosis. Here we present a 60-year-old male with metastatic melanoma to the brain. Using a transcriptomics pipeline, we analyzed whole blood and resected tumor tissue, identifying enriched gene expression biomarkers and pathways - including seven upregulated ( BRAF, CDK4, EIF1AX, IK, NRAS, PIK3R2, and TP53) and 11 downregulated (CASP8, CDK10, CDKN2A,...


• Acute Hemichorea in an Elderly Patient With Positive Anti-centromere Antibodies and Lung Tumor Fri, 19 Apr 2024 06:00:00 -0400
  Though rare, autoimmune paraneoplastic and non-paraneoplastic chorea can be leading causes of adult-onset acute/subacute chorea. Here, we report a case of acute-onset chorea with suspected autoimmune-mediated mechanisms in a 79-year-old female who exhibited acute-onset choreiform movements on the right side of her body. She tested positive for anti-centromere antibodies (ACAs) without displaying symptoms of scleroderma. Blood sugar levels, genetic testing for Huntington's disease, and an...


• Frequent loss of FAM126A expression in colorectal cancer results in selective FAM126B dependency Fri, 19 Apr 2024 06:00:00 -0400
  Most advanced colorectal cancer (CRC) patients cannot benefit from targeted therapy due to lack of actionable targets. By mining data from the DepMap, we identified FAM126B as a specific vulnerability in CRC cell lines exhibiting low FAM126A expression. Employing a combination of genetic perturbation and inducible protein degradation techniques, we demonstrate that FAM126A and FAM126B function in a redundant manner to facilitate the recruitment of PI4KIIIα to the plasma membrane for PI4P...


• Sex disparities in mortality and cardiovascular outcomes in chronic kidney disease Fri, 19 Apr 2024 06:00:00 -0400
  Sex (biologically determined) and gender (socially constructed) modulate manifestations and prognosis of a vast number of diseases, including cardiovascular disease (CVD) and chronic kidney disease (CKD). CVD remains the leading cause of death in CKD patients. Population-based studies indicate that women present a higher prevalence of CKD and experience less CVD than men in all CKD stages, although this is not as clear in patients on dialysis or transplantation. When compared to the general...


• Durable transgene expression and efficient re-administration after rAAV2.5T-mediated fCFTRdeltaR gene delivery to adult ferret lungs Fri, 19 Apr 2024 06:00:00 -0400
  The dosing interval for effective recombinant adeno-associated virus (rAAV)-mediated gene therapy of cystic fibrosis lung disease remains unknown. Here, we assessed the durability of rAAV2.5T-fCFTRΔR-mediated transgene expression and neutralizing antibody (NAb) responses in lungs of adult wild-type ferrets. Within the first 3 months following rAAV2.5T-fCFTRΔR delivery to the lung, CFTRΔR transgene expression declined ∼5.6-fold and then remained stable to 5 months at ∼26% the level of endogenous...


• A novel dual mechanism-of-action bispecific PD-1-IL-2v armed by a "βγ-only" interleukin-2 variant Fri, 19 Apr 2024 06:00:00 -0400
  INTRODUCTION: Interleukin-2 (IL-2) is one of the first cytokines to be discovered as an immune agonist for cancer immunotherapy. Biased IL-2 variants had been discovered to eliminate Treg activation or enhance the tumor specific T cell cytotoxicity. However, all the biased IL-2 variants pose the risk to overstimulate immune response at a low-dose range. Here, we introduce a novel dual-MOA bispecific PD-1-IL-2v molecule with great anti-tumor efficacy in a high dosed manner.


• Safety and efficacy of anlotinib combined with taxane and lobaplatin in neoadjuvant treatment of clinical stage II/III triple-negative breast cancer in China (the neoALTAL trial): a single-arm, phase 2 trial Fri, 19 Apr 2024 06:00:00 -0400
  BACKGROUND: Anlotinib is a new type of tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1/2/3, platelet-derived growth factor receptors α/β, and fibroblast growth factor receptors 1-4 and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. It has been proven effective in HER2-negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the...


• RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway Fri, 19 Apr 2024 06:00:00 -0400
  CONCLUSIONS: Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction, highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.


• Cervicomediastinal Hematoma: Atypical Presentation of a Parathyroid Carcinoma Fri, 19 Apr 2024 06:00:00 -0400
  Parathyroid carcinoma (PC) is a rare endocrine neoplasm that typically presents with osteopenia/osteoporosis, nephrolithiasis, asthenia, and neuropsychiatric symptoms. We describe the case of a 48-year-old woman, presenting with a large painful hematoma in the cervicomediastinal area. The neck ultrasound (US) demonstrated a solid lesion measuring 40 × 80 × 55 mm, markedly hypoechoic, which extended from the right thyroid lobe to the mediastinum. The blood tests showed elevated serum calcium and...


• Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial Fri, 19 Apr 2024 06:00:00 -0400
  CONCLUSION: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study.


• TMC function, dysfunction, and restoration in mouse vestibular organs Fri, 19 Apr 2024 06:00:00 -0400
  Tmc1 and Tmc2 are essential pore-forming subunits of mechanosensory transduction channels localized to the tips of stereovilli in auditory and vestibular hair cells of the inner ear. To investigate expression and function of Tmc1 and Tmc2 in vestibular organs, we used quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization - hairpin chain reaction (FISH-HCR), immunostaining, FM1-43 uptake and we measured vestibular evoked potentials (VsEPs) and vestibular ocular...


• Personalized treatment with PARP inhibitors in advanced urothelial carcinoma: a case report and literature review Fri, 19 Apr 2024 06:00:00 -0400
  Bladder cancer (BC) poses a significant health challenge, particularly in metastatic cases, where the prognosis is unfavorable and therapeutic options are limited. Poly ADP-ribose polymerase (PARP) inhibitors have gained approval for use in various cancer types, but their application in BC remains controversial, despite the notable prevalence of DNA damage response alterations in advanced or metastatic urothelial carcinomas. In this report, we describe a 66-year-old heavy-smoking female...


• Recurrent immunosuppressive-responsive myocarditis in a patient with desmoplakin cardiomyopathy: a case report Fri, 19 Apr 2024 06:00:00 -0400
  BACKGROUND: Desmoplakin (DSP) cardiomyopathy is a rare genetic condition characterized by repeated inflammatory myocardial injury and is associated with ventricular arrhythmia and sudden cardiac death. Diagnosis is challenging and requires a combination of genetic testing and advanced imaging techniques.


• Small fibre neuropathy in Fabry disease: a human-derived neuronal in vitro disease model and pilot data Fri, 19 Apr 2024 06:00:00 -0400
  Acral burning pain triggered by fever, thermal hyposensitivity and skin denervation are hallmarks of small fibre neuropathy in Fabry disease, a life-threatening X-linked lysosomal storage disorder. Variants in the gene encoding alpha-galactosidase A may lead to impaired enzyme activity with cellular accumulation of globotriaosylceramide. To study the underlying pathomechanism of Fabry-associated small fibre neuropathy, we generated a neuronal in vitro disease model using patient-derived induced...


• Navigating equity in global access to genome therapy expanding access to potentially transformative therapies and benefiting those in need requires global policy changes Fri, 19 Apr 2024 06:00:00 -0400
  In December 2023, the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency granted the first regulatory approval for genome therapy for sickle cell disease. This approval brings hope to those suffering from this debilitating genetic disease. However, several barriers may hinder global patient access, including high treatment costs, obtaining informed consent for minors, inadequate public health infrastructure, and insufficient regulatory oversight. These...


• In vitro human cell culture models in a bench-to-bedside approach to epilepsy Fri, 19 Apr 2024 06:00:00 -0400
  Epilepsy is the most common chronic neurological disease, affecting nearly 1%-2% of the world's population. Current pharmacological treatment and regimen adjustments are aimed at controlling seizures; however, they are ineffective in one-third of the patients. Although neuronal hyperexcitability was previously thought to be mainly due to ion channel alterations, current research has revealed other contributing molecular pathways, including processes involved in cellular signaling, energy...


• The efficacy of Carbamylglutamate impacts the nutritional management of patients with N-Acetylglutamate synthase deficiency Thu, 18 Apr 2024 06:00:00 -0400
  CONCLUSIONS: Follow-up of patients with NAGS deficiency should include plans for illness and for disruption of carbamylglutamate access, including nutrition management strategies such as protein restriction. Carbamylglutamate can help patients with NAGS deficiency to liberalize their diets, but the maximum safe level of protein intake to prevent hyperammonemia is not yet known. Patients using this medication should still monitor their diet closely and be prepared for any disruptions in...


• Genetic diagnosis of endocrine disorders in Cyprus through the Cyprus Institute of Neurology and Genetics: an ENDO-ERN Reference Center Thu, 18 Apr 2024 06:00:00 -0400
  The report covers the current and past activities of the department Molecular Genetics-Function and Therapy (MGFT) at the Cyprus Institute of Neurology and Genetics (CING), an affiliated Reference Center for the European Reference Network on Rare Endocrine Conditions (Endo-ERN).The presented data is the outcome of > 15 years long standing collaboration between MGFT and endocrine specialists from the local government hospitals and the private sector. Up-to-date > 2000 genetic tests have been...


• Construction and verification of a histone deacetylases-related prognostic signature model for colon cancer Thu, 18 Apr 2024 06:00:00 -0400
  Histone deacetylases (HDACs) contribute significantly to the initiation, progression, and prognosis of colorectal adenocarcinoma (COAD). Additionally, HDACs regulate the tumor microenvironment, immune escape, and tumor stem cells, and are closely linked to COAD prognosis. We developed a prognostic model for COAD that incorporates HDACs to evaluate their specific roles. The COAD dataset containing clinical and mutation data was collected using the TCGA and GEO databases to obtain genes associated...