A randomised, controlled phase 1 study to investigate the safety and efficacy of orally administered squalamine in subjects with Motor Neuron Disease

Motor Neuron Disease (MND) is a fatal neurodegenerative disease. MND is thought to arise from a combination of genetic susceptibility and environmental exposure, possibly due to a multi-stage process. There is considerable evidence that gut health is important in human disease and particularly in neurodegenerative disease. Given the lack of proven therapies in MND, there is an urgent need for new approaches. A range of approaches have been suggested and could involve diet, probiotics, prebiotics or antibiotics or therapies to antagonize the effects of the toxic molecules. This trial will study the effects of squalamine, an antibacterial first discovered in the dogfish shark that has a novel mode of action, and its efficacy as treatment aimed at improving gut health in MND patients. Squalamine is effective against methanobacter, which are difficult to detect, but are the likely organism responsible for methylation by gut microbes. Squalamine is rare, being one of the few non-toxic antibacterials which is active against this class of gut microbes. Squalamine is an attractive candidate because it is already widely available as a natural product in the dietary supplement Squalamax. This study will assess the safety and efficacy of squalamine (at a daily dose of 1.2 mg) in the dietary supplement Squalamax in patients with MND. The study includes 2 main periods: an unblinded treatment period (3 months) and an open label long term follow up phase (9 months). Patients in the standard care arm (i.e. no drug) will be switched to Squalamax treatment after 3 months. This study will test: - the tolerability of squalamine in patients with MND (indicated by diarrhoea or other symptoms). - the effects of squalamine on levels of gut derived toxins (before and after treatment with squalamine) - the effects of squalamine on levels of gut microbes in MND patients (collection of faecal samples for later analysis) - the effects of squalamine on MND standardised assessments (Amyotrophic Lateral Sclerosis Revised Functional Rating Scale (ALS-FRS R), Respiratory function testing (RFT)) and comparing treated and untreated patients over 3 months.