Factor IX(Sangamo Therapeutics, Inc.)

Neurodegenerative disorders are among the most common diseases in modern society. However, the molecular bases of diseases such as multiple sclerosis or Charcot-Marie-Tooth disease remain far from being fully understood. Research in this field is limited by the complex nature of native myelin and by difficulties in obtaining good in vitro model systems of myelin. Here, we introduce an easy-to-use model system of the myelin sheath that can be used to study myelin proteins in a native-like yet well-controlled environment. To this end, we present myelin-mimicking nanodiscs prepared through one of the amphiphilic copolymers styrene/maleic acid (SMA), diisobutylene/maleic acid (DIBMA), and styrene/maleimide sulfobetaine (SMA-SB). These nanodiscs were tested for their lipid composition using chromatographic (HPLC) and mass spectrometric (MS) methods and, utilizing spin probes within the nanodisc, their comparability with liposomes was studied. In addition, their binding behavior with bovine myelin basic protein (MBP) was scrutinized to ensure that the nanodiscs represent a suitable model system of myelin. Our results suggest that both SMA and SMA-SB are able to solubilize the myelin-like (cytoplasmic) liposomes without preferences for specific lipid headgroups or fatty acyl chains. In nanodiscs of both SMA and SMA-SB (called SMA(-SB)-lipid particles, short SMALPs or SMA-SBLPs, respectively), the polymers restrict the lipids' motion in the hydrophobic center of the bilayer. The headgroups of the lipids, however, are sterically less hindered in nanodiscs when compared with liposomes. Myelin-like SMALPs are able to bind bovine MBP, which can stack the lipid bilayers like in native myelin, showing the usability of these simple, well-controlled systems in further studies of protein-lipid interactions of native myelin.

To evaluate the entomological efficacy and the residual activity of indoor residual spraying with Fludora®Fusion 562.5 WP‐SB, a combination formulation containing clothianidin, a neonicotinoid and deltamethrin, a pyrethroid, against the main rural malaria vector,Anopheles culicifacies s.l., in India in a small‐scale trial.

In three study villages, suitable households were randomly allocated to five treatments: Fludora®Fusion 562.5 WP‐SB (target dose 225 mg active ingredient AI/m2); clothianidin 70 WG (target dose 200 mg AI/m2); K‐Othrine 250 WG (deltamethrin, target dose 25 mg AI/m2); Ficam VC 80 WP‐SB (bendiocarb, target dose 400 mg AI/m2) and unsprayed control. Insecticides were sprayed by hand compression sprayers with control flow valves and 8002E nozzles. Post‐spray cone bioassays were done on insecticide‐treated walls using a colonised, deltamethrin‐resistant strain ofAn. culicifacies. Mosquitoes were collected from treated rooms by different methods. The insecticide content on filter papers collected from the sprayed walls was determined by chemical assay to assess the spray quality.

The ratios of applied to target doses of insecticides were within 0.84 to 1.4, showing a good spray quality. The cone bioassays revealed residual action lasting 7 months for all insecticides without significant differences in mortality between different surfaces treated nor between the four treatment arms (P > 0.05). Considering all entomological parameters such as indoor resting density, excito‐repellency, blood‐feeding inhibition and delayed mortality, the overall efficacy of Fludora®Fusion WG‐SB was equal or better compared with other insecticides.

Fludora®Fusion showed overall equal or better efficacy than deltamethrin and bendiocarb alone against a pyrethroid‐resistant malaria vector population and can be considered as an alternative product for management of pyrethroid resistance in malaria vectors.