Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis

Introduction Long-term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such data are presented for velmanase alfa in the treatment of alpha-mannosidosis (AM). Methods Patient data (n = 33; 14 adults, 19 paediatric) from the clinical development programme for velmanase alfa were integrated in this prospectively-designed analysis of long-term efficacy and safety. Patients who participated in the phase I/II or phase III trials and were continuing to receive treatment after completion of the trials were invited to participate in a comprehensive evaluation visit to assess long-term outcomes. Primary endpoints were changes in serum oligosaccharide and the 3-minute stair climb test (3MSCT). Results Mean (SD) treatment exposure was 29.3 (15.2) months. Serum oligosaccharide levels were significantly reduced in the overall population at 12 months (mean change: –72.7%, P < 0.001) and remained statistically significant at last observation (−62.8%, P < 0.001). A mean improvement of +9.3% in 3MSCT was observed at 12 months (P = 0.013), which also remained statistically significant at last observation (+13.8%, P = 0.004), with a more pronounced improvement detected in the paediatric subgroup. No treatment-emergent adverse events were reported leading to permanent treatment discontinuation. Conclusions Patients treated with velmanase alfa experienced improvements in biochemical and functional measures that were maintained for up to 4 years. Long term follow-up is important and further supports the use of velmanase alfa as an effective and well-tolerated treatment for AM. Based on the currently available data set, no baseline characteristic can be predictive of treatment outcome. Early treatment during paediatric age showed better outcome in functional endpoints

Substituent effect on redox potential of terephthalate-based electrode materials for lithium batteries

The substituent effect on the redox potential of lithium terephthalate was studied using symmetrical dilithium disubstituted-terephthalates incorporating bromo, methoxy and amino groups. All the terephthalate derivatives have been synthesized and evaluated as anode material for lithium-ion batteries. The electrochemical results revealed an increase in the reduction potential in the case of bromo and methoxy groups and almost the same in the case of amino group compared to unmodified dilithium terephthalate. In addition, a very first tendency between the 13C chemical shifts and FTIR signal of the carbonyl and the reduction potential of the studied disubstituted-terephthalates was formulated. Keywords: Organic anode materials, Substituent effect, Structure-property relationships, Lithium batterie

Anodic oxidation of p-phenylenediamines in battery grade electrolytes

International audienceThe use of anion-inserting organic electrode materials represents an interesting opportunity for developing ‘metal-free’ rechargeable batteries. Recently, crystallized conjugated diamines have emerged as new host materials able to accommodate anions upon oxidation at potentials higher than 3 V vs. Li+/Li0 in carbonate-based battery electrolytes. To further investigate the electrochemical behavior of such promising systems, comparison with electroanalytical data of soluble forms of conjugated diamines measured in battery grade electrolytes appeared quite useful. However, the literature on the topic is generally poor since such electrolyte media are not common in molecular electrochemistry. This contribution aims at providing relevant data on the characterization by cyclic voltammetry of unsubstituted, diphenyl-substituted and tetramethyl-substituted p-phenylenediamines. Basically, these three molecules revealed two reversible one-electron reaction upon oxidation corresponding to the electrogenerated radical cation and dication, respectively, combined with the association of electrolyte anions (i.e., PF6 −, ClO4 − and TfO−). The nature of the counter-anion did not show much influence on the electrochemical activity, which remained governed by the solvation process in high-polarity solvents (i.e., PC- or EC-based battery electrolytes). However, in presence of PF6 −, the emergence of a pre-peak prior to the second oxidation step was observed when labile protons exist in the radical cation state. This contribution is attributed to a deprotonation reaction of the radical cation induced by the catalytic decomposition of PF6 − in presence of H+, which supports well the few other experimental data reported on the decomposition issues of LiPF6. In addition, substitution of the amine redox centers with appropriate functional groups (that increase the molecule π-delocalization) allowed to reach higher formal potentials without impacting the bi-electronic behavior and the reversibility of the processes

Decreasing redox voltage of terephthalate-based electrode material for Li-ion battery using substituent effect

International audienceThe preparation and assessment versus lithium of a functionalized terephthalate-based as a potential new negative electrode material for Li-ion battery is presented. Inspired from molecular modelling, a decrease in redox potential is achieved through the symmetrical adjunction of electron-donating fragments (–CH3) on the aromatic ring. While the electrochemical activity of this organic material was maximized when used as nanocomposite and without any binder, the potential is furthermore lowered by 110 mV upon functionalization, consistently with predicted value gained from DFT calculations

Electrochemical reactivity of lithium chloranilate vs Li and crystal structures of the hydrated phases

Li-ion batteries based on active organic electrode materials may present an alternative route to the current battery technology, particularly in terms of recycling cost. Here, we report preliminary data regarding the electrochemical behavior of Li2 C6 O4 Cl2 obtained by dehydration of the dilithium chloranilate monohydrate, which is formed by spontaneous dehydration of the Li2 C6 O4 Cl2 ∼6 H2 O phase. Electrochemically tested vs Li, the anhydrous chloranilate displays a reversible capacity of 200 mAh g-1 at an average potential of 2.3 V, which slightly decays upon cycling as opposed to Li2 C6 O4 Cl2 H2 O. Moreover, thermal recycling of chloranilate phases leads to the LiCl formation, which is a benign salt. © 2009 The Electrochemical Society

An air-stable lithiated cathode material based on a 1,4-benzenedisulfonate backbone for organic Li-ion batteries

International audienc

An air-stable lithiated cathode material based on a 1,4-benzenedisulfonate backbone for organic Li-ion batteries

International audienceTo meet current market demands as well as emerging environmental concerns there is a need to develop less polluting battery technologies

Lithium salt of tetrahydroxybenzoquinone: Toward the development of a sustainable Li-ion battery

The use of lithiated redox organic molecules containing electrochemically active C=O functionalities, such as lithiated oxocarbon salts, is proposed. These represent alternative electrode materials to those used in current Li-ion battery technology that can be synthesized from renewable starting materials. The key material is the tetralithium salt of tetrahydroxybenzoquinone (Li 4C6O6), which can be both reduced to Li 2C6O6 and oxidized to Li6C 6O6. In addition to being directly synthesized from tetrahydroxybenzoquinone by neutralization at room temperature, we demonstrate that this salt can readily be formed by the thermal disproportionation of Li2C6O6 (dilithium rhodizonate phase) under an inert atmosphere. The Li4C6O6 compound shows good electrochemical performance vs Li with a sustained reversibility of ∼200 mAh g-1 at an average potential of 1.8 V, allowing a Li-ion battery that cycles between Li2C6O6 and Li 6C6O6 to be constructed. © 2009 American Chemical Society