Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects. 50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs). In both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env. The present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1 may offer new perspectives for treating CIDP patients with positive detection of MSRV-Env expression. Geneuro-Innovation, France

Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium

International audiencePrevious studies have tested gene replacement therapy in RPE65-deficient dogs using recombinant adeno-associated virus 2/2 (rAAV2/2), -2/1 or -2/5 mediated delivery of the RPE65 gene. They all documented restoration of dark- and light-adapted electroretinography responses and improved psychophysical outcomes. Use of a specific RPE65 promoter and a rAAV vector that targets transgene expression specifically to the RPE may, however, provide a safer setting for the long-term therapeutic expression of RPE65. Subretinal injection of rAAV2 pseudotyped with serotype 4 (rAAV2/4) specifically targets the RPE. The purpose of our study was to evaluate a rAAV2/4 vector carrying a human RPE65cDNA driven by a human RPE65 promoter, for the ability to restore vision in RPE65-/- purebred Briard dogs and to assess the safety of gene transfer with respect to retinal morphology and function. rAAV2/4 and rAAV2/2 vectors containing similar human RPE65 promoter and cDNA cassettes were generated and administered subretinally in eight affected dogs, ages 8–30 months (n=6 with rAAV2/4, n=2 with rAAV2/2). Although fluorescein angiography and optical coherence tomography examinations displayed retinal abnormalities in treated retinas, electrophysiological analysis demonstrated that restoration of rod and cone photoreceptor function started as soon as 15 days post-injection, reaching maximal function at 3 months post-injection, and remaining stable thereafter in all animals treated at 8–11 months of age. As assessed by the ability of these animals to avoid obstacles in both dim and normal light, functional vision was restored in the treated eye, whereas the untreated contralateral eye served as an internal control. The dog treated at a later age (30 months) did not recover retinal function or vision, suggesting that there might be a therapeutic window for the successful treatment of RPE65-/- dogs by gene replacement therapy

Reflectância espectral e mineralogia de materiais formados sobre diabásio Spectral reflectance and mineralogy of soil materials developed from diabase

O presente estudo teve por objetivo caracterizar diferentes fases de intemperismo de um solo e relacioná-las com seu comportamento espectral. Um perfil pedológico desenvolvido sobre diabásio da região de Capivari-SP, foi descrito morfologicamente, identificando-se seis fases de alteração. Os atributos analisados foram granulometria, composição química e mineralógica. A reflectância espectral do solo foi avaliada em laboratório através de espectrorradiômetro na faixa de 300 a 2500 nm. O perfil apresentou grau de intemperismo moderado, o que foi evidenciado pela alta relação silte/argila observada abaixo do horizonte Bi. Os horizontes subsuperficiais também apresentaram alto teor de nutrientes, especialmente P, Ca e Mg, que estavam relacionados com a presença em subsuperfície de saprolito com razoável reserva de minerais intemperizáveis. A evolução dos minerais primários iniciou pela formação de óxidos de ferro e de argilas 2:1, como vermiculita ou vermiculita-esmectita, que foram transformadas em caulinita e gibbsita em direção ao topo do perfil. Na medida em que ocorreram alterações na composição mineralógica no perfil, foram verificadas variações nos dados espectrais. Basicamente a reflectância foi influenciada diferenciadamente pela ocorrência de óxidos de ferro, diferentes tipos de argilas e minerais primários como piroxênios e magnetita.<br>The aim of this study was to characterize soil materials with different degrees of weathering and then associate their composition with their spectral behavior. One pedological profile developed from diabase was studied in Capivari-SP, Brazil. The morphological description allowed to separate six phases of rock-soil alteration. Afterwards, granulometry, chemical and mineralogical analysis were carried out. The soil spectral reflectance was evaluated with a laboratory spectroradiometer using the wavelength range of 300 to 2500 nm. The profile was moderately weathered as evidenced by a high silt/clay ratio, found below the Bi horizon. Subsurface horizons also presented high nutrient status, especially for P, Ca and Mg, which was related to the occurence of saprolite with an abundance of easily weathered minerals. The mineral evolution began with the precipitation of iron oxides and 2:1 clay minerals, like vermiculite and vermiculite-smectite, and this led to the formation of kaolinite and gibbsite in the upper part of the soil profile. Spectral behavior generally was in conformity with their mineralogical composition, pointing out to the presence of iron oxides, various groups of clays and primary minerals, such as pyroxenes and magnetite