The purpose of this study is to determine the safety and tolerability of RNS60 in patients with Amyotrophic lateral sclerosis (ALS). Investigators will also measure the impact of RNS60 on several markers of neuro-inflammation, measured by blood biomarkers and positron emission tomography (PET) imaging.
Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease for which there is no cure. A substantial body of evidence implicates the neuroimmune system in ALS pathophysiology. Of relevance to this study, microglia activation in the brain has been found to correlate positively with faster rate of disease progression. In addition, studies of blood cells in people with ALS have shown an increased activation of two of the major inflammatory cell types in the body, monocytes and T cells. Among T cells, regulatory T cells (Tregs) have been recently proposed to play a role in ALS progression.
RNS60 is an electrokinetically altered aqueous fluid. Chemically, RNS60 is composed of saline and oxygen. The electrokinetic processing of RNS60 in Revalesio's patented Revalesio Pump (RP) produces charge-stabilized nanostructures (CSNs) that exhibit electrical fields. RNS60 is available for intravenous administration and inhalation. RNS60 has been extensively tested in preclinical toxicological studies and has shown very little to no side effects. In addition, RNS60 was well tolerated in three phase I human safety studies, one after intravenous administration and two after inhalation.
Preclinical in vitro and in vivo studies in multiple disease models have demonstrated that RNS60 has broad anti-inflammatory effects. These effects include reduction of microglia activation, increase of the Tregs subpopulation of lymphocytes, and neuroprotection in several disease models.
Inclusion Criteria:
Exclusion Criteria:
Abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine transaminase (ALT) > 3 times the upper limit of the normal.
Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal.
The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the participant to provide informed consent, according to PI judgment.
Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant if they were to participate in the study.
History of HIV, clinically significant chronic hepatitis, or other active infection.
Females must not be lactating or pregnant.
Active participation in another ALS clinical trial within 30 days of the Screening Visit
Exposure to immunomodulatory medications within 30 days of the Screening Visit.
Any contraindication to undergo MRI studies such as
Radiation exposure that exceeds the site's current guidelines
Current use of tobacco products including cigarettes, cigars, snuff and chewing tobacco, or nicotine replacement products such as gum or patch