ILB® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis

Giacomo Lazzarino; Renata Mangione; Antonio Belli; Valentina Di Pietro; Zsuzsanna Nagy; Nicholas M Barnes; Lars Bruce; Bernardo M Ropero; Lennart I Persson; Benedetta Manca; Miriam Wissam Saab; Angela M Amorini; Barbara Tavazzi; Giuseppe Lazzarino; Ann Logan

doi:10.3390/jpm11080794

ILB^® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis

J Pers Med. 2021 Aug 14;11(8):794. doi: 10.3390/jpm11080794.

Authors

Giacomo Lazzarino¹, Renata Mangione^{2

3}, Antonio Belli⁴, Valentina Di Pietro⁴, Zsuzsanna Nagy⁴, Nicholas M Barnes⁴, Lars Bruce⁵, Bernardo M Ropero⁶, Lennart I Persson⁶, Benedetta Manca⁷, Miriam Wissam Saab⁸, Angela M Amorini⁸, Barbara Tavazzi^{1

2

3}, Giuseppe Lazzarino⁸, Ann Logan^{9

10}

Affiliations

¹ UniCamillus, Saint Camillus International University of Health Sciences, 00131 Rome, Italy.
² Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Rome, 00168 Rome, Italy.
³ Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
⁴ College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
⁵ Tikomed AB, 263 03 Viken, Sweden.
⁶ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, 413 90 Gothenburg, Sweden.
⁷ Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy.
⁸ Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, 95123 Catania, Italy.
⁹ Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
¹⁰ Axolotl Consulting Ltd., Droitwich WR9 0JS, UK.

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^®. 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^® treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes.

Keywords: HPLC; N-acetylaspartate; amino acids; amyotrophic lateral sclerosis; antioxidants; energy metabolism; low molecular weight-dextran sulphate; mitochondrial dysfunction; oxidative/nitrosative stress; serum biomarkers.