Background: Leber Hereditary Optic Neuropathy (LHON) is a rare, maternally-inherited mitochondrial disease that primarily affects retinal ganglion cells (RGCs) and their axons in the optic nerve, leading to irreversible, bilateral severe vision loss. Lenadogene nolparvovec gene therapy was developed as a treatment for patients with vision loss from LHON caused by the most prevalent m.11778G > A mitochondrial DNA point mutation in the MT-ND4 gene.
View Article and Find Full Text PDFRespiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections (LRTI) in infants, and toddlers and vaccines are not yet available. A pediatric RSV vaccine (ChAd155-RSV) is being developed to protect infants against RSV disease. The ChAd155-RSV vaccine consists of a recombinant replication-deficient chimpanzee-derived adenovirus (ChAd) group C vector engineered to express the RSV antigens F, N, and M2-1.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
December 2021
Lenadogene nolparvovec (Lumevoq) gene therapy was developed to treat Leber hereditary optic neuropathy (LHON) caused by the m.11778G > A in that affects complex I of the mitochondrial respiratory chain. Lenadogene nolparvovec is a replication-defective, single-stranded DNA recombinant adeno-associated virus vector 2 serotype 2, containing a codon-optimized complementary DNA encoding the human wild-type subunit protein.
View Article and Find Full Text PDFThere is a growing need to consider non-rodent species for the immunological safety evaluation of drug candidates. The EU Framework-6 RETHINK Project demonstrated that the Göttingen Minipig is a relevant animal model for regulatory toxicology studies. Extensive knowledge on the immune system of domestic pigs is available and fewer differences from humans have been identified as compared to other species, such as mice or non-human primates.
View Article and Find Full Text PDFObjective: Colony-stimulating factor 1 receptor (CSF-1R) essentially modulates monocyte proliferation, migration, and activation, which are considered important for the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine CSF-1R expression in human RA as well as the efficacy of a specific anti-CSF-1R monoclonal antibody (AFS98) in 2 different animal models of RA.
Methods: CSF-1R expression was examined in blood, synovium, and bone samples from RA patients, osteoarthritis (OA) patients, and healthy subjects.
The humanized monoclonal antibody H27K15 specifically targets human CD115, a type III tyrosine kinase receptor involved in multiple cancers and inflammatory diseases. Binding of H27K15 to hCD115 expressing cells inhibits the functional effect of colony-stimulating factor-1 (CSF-1), in a non-competitive manner. Both homology modeling and docking programs were used here to model the human CD115 extracellular domains, the H27K15 variable region and their interaction.
View Article and Find Full Text PDFCancer progression has been associated with the presence of tumor-associated M2-macrophages (M2-TAMs) able to inhibit anti-tumor immune responses. It is also often associated with metastasis-induced bone destruction mediated by osteoclasts. Both cell types are controlled by the CD115 (CSF-1R)/colony-stimulating factor-1 (CSF-1, M-CSF) pathway, making CD115 a promising target for cancer therapy.
View Article and Find Full Text PDFTherapeutic vaccines are different from the well-known prophylactic vaccines in that they are designed to treat patients already suffering from a disease instead of preventing the disease in healthy individuals. Several therapeutic vaccines are today in late-stage clinical development for non-small-cell lung cancer. These vaccines use different approaches including peptides, cell lines and viral vectors, and explore different settings within the pathology.
View Article and Find Full Text PDFJ Pharmacol Toxicol Methods
January 2011
The potential of the minipig as a platform for future developments in genomics, high density biology, transgenic technology, in vitro toxicology and related emerging technologies was reviewed. Commercial interests in the pig as an agricultural production species have driven scientific progress in these areas. There is no equivalent economic driver for progress in the dog or the monkey.
View Article and Find Full Text PDFCisplatin is a chemotherapeutic agent whose use is limited by side effects including neuropathies. In proliferating cells, toxic action of cisplatin is based on DNA interactions, while, in quiescent cells, it can induce apoptosis by interacting with proteins. In the present study, we compared cytotoxic mechanisms activated by cisplatin in primate and rodent neurons and in ovary cells in order to determine whether the anti-apoptotic peptide PACAP could selectively reduce neurotoxicity.
View Article and Find Full Text PDFIntrinsic ageing of human skin is a subtle and gradual process that demonstrates few clinical or histological features until old age (>70 years). Initial work indicates that aged skin is "retinoid sensitive" but there is little data on the role of retinoic acid receptors (RARs) or retinoid X receptors (RXRs) in skin ageing. As nuclear retinoid receptors have been implicated in ageing in rodents, we studied the distribution of these receptors in intrinsically aged as compared to young, photoprotected human skin.
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