A multi-center, randomized, active controlled clinical trial to evaluate the efficacy and safety of OTL-203 in subjects with mucopolysaccharidosis type I, Hurler syndrome (MPS-IH) compared to standard of care with allogeneic hematopoietic stem cell transplantation (allo-HSCT) - OTL-203-02

开始日期2024-09-27

申办/合作机构

Orchard Therapeutics (Europe) Ltd.

EUCTR2019-002636-82-IT / Unknown status临床3期

An open label, non-randomised trial to evaluate the safety and efficacy of a single infusion of OTL-200 in patients with Late Juvenile (LJ) Metachromatic Leukodystrophy (MLD)

开始日期2019-12-02

申办/合作机构

Orchard Therapeutics (Europe) Ltd.

EUCTR2017-001731-39-IT / Not yet recruiting临床4期

Methodology study to investigate the utility of retroviral insertion site analysis in samples from subjects treated with Strimvelis™ gene therapy - Retroviral insertion site methodology study

开始日期2017-10-12

申办/合作机构

Orchard Therapeutics (Europe) Ltd.

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项与 Orchard Therapeutics (Europe) Ltd. 相关的文献（医药）

2024-05-01·Molecular Genetics and Metabolism

Higher precision, first tier newborn screening for metachromatic leukodystrophy using 16:1-OH-sulfatide

Article

作者: Bekri, Soumeya ; Gelb, Michael H ; Mechtler, Thomas ; Hong, Xinying ; Janzen, Nils ; Wu, Teresa H Y ; Tebani, Abdellah ; Bley, Annette ; Brown, Heather A ; Chanson, Charlotte ; Oliva, Petra ; Church, Heather J ; Morton, Georgina ; Murko, Simona ; Kasper, David C

Newborn screening (NBS) for metachromatic leukodystrophy (MLD) is based on first-tier measurement of sulfatides in dried blood spots (DBS) followed by second-tier measurement of arylsulfatase A in the same DBS. This approach is very precise with 0-1 false positives per ∼30,000 newborns tested. Recent data reported here shows that the sulfatide molecular species with an α-hydroxyl, 16‑carbon, mono-unsaturated fatty acyl group (16:1-OH-sulfatide) is superior to the original biomarker 16:0-sulfatide in reducing the number of first-tier false positives. This result is consistent across 4 MLD NBS centers. By measuring 16:1-OH-sulfatide alone or together with 16:0-sulfatide, the estimated false positive rate is 0.048% and is reduced essentially to zero with second-tier arylsulfatase A activity assay. The false negative rate is predicted to be extremely low based on the demonstration that 40 out of 40 newborn DBS from clinically-confirmed MLD patients are detected with these methods. The work shows that NBS for MLD is extremely precise and ready for deployment. Furthermore, it can be multiplexed with several other inborn errors of metabolism already tested in NBS centers worldwide.

2024-01-24·Journal of Crohn's and Colitis

OP29 Haematopoietic stem cell gene therapy as a treatment for severe Crohn’s Disease associated with pathogenic NOD2 genetic variants

作者: del Mar Masdeu, M ; Zabinski, T ; Recchi, C ; Narean, J S ; Whiting, C ; Gaspar, B ; Luiz, A ; Mavilio, F ; Heal, P ; Du, L ; Pennucci, V ; Elavazhagan, S ; Enjalbert, F ; Cattoni, M ; Sagoo, P

AbstractBackgroundPathogenic variants of the NOD2 (nucleotide-binding oligomerization domain containing protein 2) gene demonstrate the strongest genetic association to Crohn’s inflammatory bowel disease (CD), with mounting evidence linking NOD2 deficiency with poor clinical outcome. CD patients with NOD2 variants, particularly carriers of more than one risk allele, frequently present an aggressive, fistulizing and fibrostenotic disease, requiring multiple surgical resections. NOD2-deficiency is implicated to drive CD pathogenesis through failure of gut innate immunity to resolve bacterial infections and by loss of tissue homeostasis within the intestinal microenvironment. Here we present preclinical data on OTL-104, an autologous haematopoietic stemcell gene therapy (HSC-GT) which aims to stably restore NOD2 expression in gut resident macrophages, to correct immune dysfunction linked to NOD2-deficient CD pathogenesis.MethodsWe used in vitro and in vivo models of NOD2 deficiency to demonstrate the mechanism of action and the efficacy of OTL-104 autologous HSC-GT.ResultsNOD2KO human myeloid cells differentiated in vitro from CRISPR-generated NOD2KO CD34+ HSCs are unable to mount a proinflammatory cytokine response to MDP stimulation. Similarly, myeloid cells differentiated from CD34+ cells obtained from peripheral blood of genetically characterized NOD2-deficient CD patients, are also refractory to MDP stimulation and unable to generate a normal cytokine response profile. In both NOD2 deficient CD34+ derived monocyte models, transduction with a lentiviral vector (LVV) expressing NOD2 fully restores NOD2-dependent cytokine and chemokine responses, restoring an immune profile that is comparable to monocytes derived from CD34+ cells from NOD2 wild-type healthy donors (Figure 1).Transplantation of lineage negative (Lin-) haematopoietic stem/progenitor cells (HSPCs) transduced with the OTL-104 LVV in NOD2KO mice was used as an in vivo model of gene therapy for CD. Compared to WT mice, NOD2KO mice fail to release systemic inflammatory mediators and recruit myeloid cells in response to MDP administration. Transplantation of transduced Lin- HSPCs restores MDP-induced systemic release of IL-6 and CXCL1 as well as innate mobilization of monocyte/macrophage cells and gut associated gene expression. Key to our therapeutic approach, histopathological analysis of intestinal lamina propria from transplanted mice shows a normal biodistribution and physiological NOD2 gene expression in tissue resident cells.ConclusionThese results confirm the impact of NOD2 deficiency in primary immune activation and demonstrates the therapeutic potential of OTL-104 HSC-GT for long-term correction of NOD2-deficient CD.

2023-03-01·Molecular Therapy

Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier

Review

作者: Gaspar, H Bobby ; Critchley, Bethan J ; Benedetti, Sara

Lysosomal storage diseases (LSDs) are multisystem inherited metabolic disorders caused by dysfunctional lysosomal activity, resulting in the accumulation of undegraded macromolecules in a variety of organs/tissues, including the central nervous system (CNS). Treatments include enzyme replacement therapy, stem/progenitor cell transplantation, and in vivo gene therapy. However, these treatments are not fully effective in treating the CNS as neither enzymes, stem cells, nor viral vectors efficiently cross the blood-brain barrier. Here, we review the latest advancements in improving delivery of different therapeutic agents to the CNS and comment upon outstanding questions in the field of neurological LSDs.

项与 Orchard Therapeutics (Europe) Ltd. 相关的新闻（医药）

2022-08-18

·PRNewswire

Orchard Software Announces Monkeypox Testing at CDR Labs

CARMEL, Ind., Aug. 18, 2022 /PRNewswire/ -- Orchard Software and CDR Laboratories have partnered to rapidly implement monkeypox testing. According to the Centers for Disease Control and Prevention, the number of Monkeypox (Orthopoxvirus) cases are on the rise. To mitigate the virus' spread, laboratories must quickly identify the virus and communicate results so that timely treatment and contact tracing can take place. Miami-based CDR Laboratories is a CLIA and CAP life science laboratory that specializes in molecular diagnostics with a focus on speed of results reporting to enable faster patient care. CDR Labs also provides chemistry, toxicology, and hematology testing. Its collaboration with Orchard enables rapid reporting and response to monkeypox virus test results. "CDR Labs is proud to respond to the public health emergency to provide a safe, accurate test for identification of Monkeypox," said Sarah M.J. Helber, PhD, HCLD (ABB), Chief Laboratory Officer for CDR Labs. "Our goal is to provide efficient collection and rapid turnaround times for all our patients to curb the spread of this disease. As the first laboratory to collaborate with Orchard on implementing monkeypox testing, I was pleased with how rapidly Orchard was able to configure our LIS to process and report monkeypox results." "We are excited to partner with CDR Laboratories to facilitate rapid reporting of Monkeypox virus results to help address this public health emergency," said Billie Whitehurst, CEO of Orchard Software. "Our innovative solution provides laboratories with ordering and reporting tools that allow them to play an active part in addressing infectious disease threats." About Orchard Software Corporation Orchard Software Corporation is a leader in the laboratory information system industry and offers a variety of solutions. Orchard serves more than 2,000 laboratories across the country, helping them improve efficiency, reduce errors, and enhance integration. Orchard's cloud-based solutions are installed in physician groups and clinics, hospitals, independent reference labs, student health centers, veterinary labs, public health organizations, universities, and retail facilities. For more information regarding Orchard Software Corporation, visit . Media Contact: Steve Hurwitz, Vice President of Marketing (800) 856-1948 | [email protected] SOURCE Orchard Software Corporation

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