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- Lazzarino, G., et al.
(författare)
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ILB(R) Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in the metabolic profiles of serum from ALS patients treated weekly for 4 weeks with a repeated sub-cutaneous dose of 1 mg/kg of a proprietary low molecular weight dextran sulphate, called ILB(R). A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients' clinical conditions, indicating a response to ILB(R) treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes.
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- Nappini, S., et al.
(författare)
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Soft x-ray spectroscopies in liquids and at solid-liquid interface at BACH beamline at Elettra
- 2021
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Ingår i: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 92:1
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Tidskriftsartikel (refereegranskat)abstract
- The beamline for advanced dichroism of the Istituto Officina dei Materiali-Consiglio Nazionale delle Ricerche, operating at the Elettra synchrotron in Trieste (Italy), works in the extreme ultraviolet-soft x-ray photon energy range with selectable light polarization, high energy resolution, brilliance, and time resolution. The beamline offers a multi-technique approach for the investigation of the electronic, chemical, structural, magnetic, and dynamical properties of materials. Recently, one of the three end stations has been dedicated to experiments based on electron transfer processes at the solid/liquid interfaces and during photocatalytic or electrochemical reactions. Suitable cells to perform soft x-ray spectroscopy in the presence of liquids and reagent gases at ambient pressure were developed. Here, we present two types of static cells working in transmission or in fluorescence yield and an electrochemical flow cell that allows us to carry out cyclic voltammetry in situ and electrodeposition on a working electrode and to study chemical reactions under operando conditions. Examples of x-ray absorption spectroscopy measurements performed under ambient conditions and during electrochemical experiments in liquids are presented.
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- Logan, A., et al.
(författare)
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A phase II open label clinical study of the safety, tolerability and efficacy of ILB® for Amyotrophic Lateral Sclerosis
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Amyotrophic lateral sclerosis (ALS) is an invariably lethal progressive disease, causing degeneration of neurons and muscle. No current treatment halts or reverses disease advance. This single arm, open label, clinical trial in patients with ALS investigated the safety and tolerability of a novel modified low molecular weight dextran sulphate (LMW-DS, named ILB®) previously proven safe for use in healthy volunteers and shown to exert potent neurotrophic effects in pre-clinical studies. Secondary endpoints relate to efficacy and exploratory biomarkers. Methods Thirteen patients with ALS were treated with 5 weekly subcutaneous injections of ILB®. Safety and efficacy outcome measures were recorded weekly during treatment and at regular intervals for a further 70 days. Functional and laboratory biomarkers were assessed before, during and after treatment. Results No deaths, serious adverse events or participant withdrawals occurred during or after ILB® treatment and no significant drug-related changes in blood safety markers were evident, demonstrating safety and tolerability of the drug in this cohort of patients with ALS. The PK of ILB® in patients with ALS was similar to that seen in healthy controls. The ILB® injection elicited a transient elevation of plasma Hepatocyte Growth Factor, a neurotrophic and myogenic growth factor. Following the ILB® injections patients reported increased vitality, decreased spasticity and increased mobility. The ALSFRS-R rating improved from 36.31 ± 6.66 to 38.77 ± 6.44 and the Norris rating also improved from 70.61 ± 13.91 to 77.85 ± 14.24 by Day 36. The improvement of functions was associated with a decrease in muscle atrophy biomarkers. These therapeutic benefits decreased 3-4 weeks after the last dosage. Conclusions This pilot clinical study demonstrates safety and tolerability of ILB® in patients with ALS. The exploratory biomarker and functional measures must be cautiously interpreted but suggest clinical benefit and have a bearing on the mechanism of action of ILB®. The results support the drug's potential as the first disease modifying treatment for patients with ALS.
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