Ophthalmology 360®’s Post

#CureDuchenne is pleased to share that Wave Life Sciences announced positive interim data from the ongoing Phase 2 FORWARD-53 study in Duchenne amenable skipping exon 53. After 24 weeks of 10 mg/kg dosing every two weeks, individuals treated with WVE-N531 demonstrated an average dystrophin expression of 9.0% of normal when adjusted for muscle content (5.5% of normal dystrophin if unadjusted). Muscle biopsies also showed signs of improvement in muscle health (myofiber size and diameter) and the presence of the drug in muscle satellite cells. Serum biomarkers, such as creatine kinase (CK), were also reduced. Wave plans to complete the 48-week FORWARD-53 trial in Q1 2025 and receive feedback from regulators about a pathway to accelerated approval. READ THE PRESS RELEASE & LETTER TO THE COMMUNITY HERE: https://lnkd.in/grxpfTjW #DMD #Duchenne #exonskipping #research #FDA #WaveLifeSciences

Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level Medulloblastomas (MBs) are highly heterogeneous paediatric brain tumours that remain challenging to treat. Here, the authors integrate proteomics, epigenomics, transcriptomics and post-translational modification analyses to find molecular subgroups and potential therapeutic targets in MB tumours. https://lnkd.in/gpAZkhqH

Antisense oligonucleotides (ASOs) are promising tools in drug development that can be used to precisely control gene expression and target a range of diseases at the molecular level. Our scientists, Amy Byrnes, Casper Hoogenraad and team published in Cell Reports Methods about the development of a new pre-clinical model that emits green fluorescence in tissues when ASOs are active. This is a critical step forward in understanding how ASO activity is regulated in the body, which is important for developing ASO therapies for a wide-range of diseases. Learn more about their work: http://spr.ly/6049XUzqN Imaged is a mouse's brain, focusing on two regions known as the hippocampus and cortex. In this photo, you can observe these areas fluorescing green after injection with ASOs, shown in red.

Happy to share our article “Simple & Rapid flow cytometry assay for the detection of malignant epithelial cells in body fluids” published in CYTOPATHOLOGY. We have developed a simple and rapid flow cytometry assay for the detection of malignant epithelial cells in body fluids. We developed an antibody panel composed only of surface markers for this FCM assay to enable faster results. We compared results of cytology/cell block and FCM. This FCM assay is simple, easier and cost-effective, yielding sensitive results with no inter-observer variability. This technique will improve the diagnostic accuracy, serving as a valuable adjunct to cytology and cell block.

Unifying considerations and evidence of macrophage activation mosaicism through human CSF1R and M1/M2 genes. Summary Addressing the mononuclear phagocyte system (MPS) and macrophage M1/M2 activation is important in diagnosing hematological disorders and inflammatory pathologies and designing therapeutic tools. CSF1R is a reliable marker to identify all circulating MPS cells and tissue macrophages in humans using a single surface protein. CSF1R permits the quantification and isolation of monocyte and dendritic cell (DC) subsets in conjunction with CD14, CD16, and CD1c and is stable across the lifespan and sexes in the absence of overt pathology. Beyond cell detection, measuring M1/M2 activation in humans poses challenges due to response heterogeneity, transient signaling, and multiple regulation steps for transcripts and proteins. MPS cells respond in a conserved manner to M1/M2 pathways such as interleukin-4 (IL-4), steroids, interferon-γ (IFNγ), and lipopolysaccharide (LPS), for which we propose an ad hoc modular gene expression tool. Signature analysis highlights macrophage activation mosaicism in experimental samples, an emerging concept that points to mixed macrophage activation states in pathology.

We are pleased to announce another significant milestone with the publication of a new manuscript in bioRxiv & medRxiv, highlighting our promising genomic medicine approach intended to reduce excessive pain in patients with chronic neuropathic pain.    In this paper, we reveal engineered zinc finger repressors (ZFRs) that target the human gene encoding Nav1.7, a critical sodium channel involved in pain pathways. The paper shows, for the first time, the potency, specificity, and safety of ZFRs in nonhuman primates.    We demonstrate that our ZFRs can selectively reduce the expression of Nav1.7 sodium channels in sensory neurons – key cells that relay pain signals to the brain. We achieve potent repression of Nav1.7 following a single intrathecal administration of AAV encoding the ZFR. This promising science could play a role in the first AAV-based potential genomic medicine for neuropathic pain in the clinic, which would offer new hope for patients suffering from chronic pain conditions. Sangamo is on track to submit an Investigational New Drug (IND) application to the FDA later this year. Click here to view the new manuscript, https://bit.ly/3ZgpBtS

Our results demonstrate the potential for zinc finger repressors targeting the gene encoding Nav1.7 to reduce chronic neuropathic pain after a single treatment. We hope that in the future this new modality will help patients suffering from chronic neuropathic pain, a highly unmet need. #sangamo #neurology

Gene&Cell Therapy >> Wave rides new Phase 2 DMD data as it sets sights on accelerated approval: Wave Life Sciences said new Phase 2 biomarker data for its exon-skipping therapy are promising for certain patients with Duchenne muscular dystrophy, and it plans to discuss accelerated approval plans with the FDA early next year. The company on Tuesday disclosed the results, which come at the 24-week halfway point of the study that is testing WVE-N531 administered every two weeks in 11 boys with DMD who are amenable to exon 53 skipping. Ten of the boys are ambulatory, meaning they can still walk on their own, and one is non-ambulatory. Wave reported biomarker data from nine of the ambulatory boys, and chief development officer Anne-Marie Li-Kwai-Cheung told investors on Tuesday that the company did not have biomarker results from one boy, since his muscle biopsy was “too low-quality to be analyzed.” Wave found that muscle content-adjusted dystrophin levels were 9% of normal and average unadjusted dystrophin expression was 5.5% of normal. The biotech also said that eight of nine ambulatory boys reached muscle content-adjusted dystrophin levels that were at least 5% of normal, a sign that the boys were able to produce more of the key muscle protein. “Achieving 9% dystrophin and doing that consistently, I think, is a really transformational dataset for the field, which is so used to low inconsistent levels of dystrophin from study after study,” CEO Paul Bolno said in an interview before the news was announced. Wave’s shares $WVE jumped about 45% Tuesday morning. Anne-Marie Li-Kwai-Cheung The company noted that its data showed WVE-N531 could enter muscle stem cells, which Li-Kwai-Cheung said hasn’t been reported before with the approved gene therapy or approved exon skipping drugs to her knowledge. There are currently two approved exon 53 skipping therapies on the market — Sarepta Therapeutics’ Vyondys 53 and NS Pharma’s Viltepso. (In June, Sarepta also won a controversial broad approval of its Duchenne muscular dystrophy gene therapy.) For both exon skipping therapies, patients are dosed once a week while Wave’s experimental therapy is dosed once every two weeks in this study. The company plans to switch the enrolled boys to a once-monthly dosing regimen, citing the drug’s 61-day half-life. There were four cases of mild treatment-related adverse events reported in three boys, with no serious side effects and no study discontinuations. Li-Kwai-Cheung told investors that the treatment displayed “an extraordinarily clean profile for an exon-skipping therapy.” The company didn’t share data on functional improvements, though it expects to have final 48-week data in the first quarter of 2025. It plans to engage US regulators then to discuss the accelerated approval pathway. Bolno told investors that the company is also… #lucidquest #genetherapy #celltherapy

🌟 Integrin-Linked Kinase and Retinal Angiogenesis in FEVR 🌟 👁️ Familial Exudative Vitreoretinopathy (FEVR) is a challenging disease characterized by defective retinal angiogenesis, leading to vision complications. A study by Hongryeol Park, Hiroyuki Yamamoto, Lucas Mohn, Lea Ambühl, Kenichi Kanai, Inga Schmidt, Kee-Pyo Kim, Alessia Fraccaroli, Silke Feil, Harald Junge, Eloi Montanez, Wolfgang Berger, Ralf H. Adams investigates the role of integrin-linked kinase (ILK) in retinal angiogenesis and its connection to Wnt signaling and FEVR. 📊 Key Findings: ILK Role: ILK is crucial for retinal angiogenesis and maintaining the blood-retina barrier. Study Models: Inactivation of ILK in mice resulted in sprouting defects, reduced endothelial proliferation, and disruption of the blood-retina barrier, mirroring FEVR phenotypes. Human Impact: Mutations in ILK were identified in FEVR patients, affecting the gene product's function in vitro. 🔍 This research highlights the importance of ILK in retinal health and its potential link to Wnt signaling pathways, providing new insights into the molecular mechanisms underlying FEVR. 📚 Dive into the study to explore the detailed mechanisms and implications for clinical practice. https://lnkd.in/gariJA69 #MedicalResearch #FEVR #RetinalAngiogenesis #WntSignaling #ClinicalInsights #PhysicianUpdate #VisionHealth

Hi everyone As we all know that there is a major change in WHO 2022 classification of urinary and male genital tumors. A nice case has been diagnosed with renal tumor along with molecular technique. A 22 year old male presented to us with a history of severe flank pain associated with gross hematuria. As the hematuria was so reddish , cytology was done and per Paris system Of Reporting Urinary Lesions it was given as High Grade Intraepithelial Neoplasm. Furthermore , Ct was performed by taking proper informed consent which shows huge about 20.6 × 11.9 × 9.5 cm with heterogeneous enhancement and some calcified contents. Biopsy of the lesion revealed atypical spindle shaped cells arranged in irregular vascular channels and IHC is positive for CD31 , on the basis Angiosarcoma was given as diagnosis based on 2022 WHO classifiaction Of urinary and male genital tumors.. However, microsatellite analysis for loss of loss of heterozygosity needs to be analyzed in such cases after taking proper informed consent karyotyping is performed which shows abnormalities in chromosome 7,12,17. Note the marked areas. #squash #cytology #urineary #tract #cancers #cytogenetics #fishanalysis #on #fluid #solid #tumors #chemoradiation #rare #case #diagnosis