Current drugs being tested
Amantadine
Amantadine is a licensed drug that is mainly used in the UK for the treatment of Parkinson’s disease, and fatigue in multiple sclerosis. Amantadine interacts with messenger signalling pathways in the brain that are related to chemicals called dopamine and glutamate. Amantadine has been shown in other trials to have positive effects in other neurodegenerative conditions such as Parkinson’s disease, multiple sclerosis and Huntington’s disease. It has only been tested once in MND, where it did not show an effect, but this trial involved only on a small number of participants, and many detailed outcomes were not reported. Importantly in our laboratory studies we have shown that amantadine is effective in reducing the abnormal ‘clumping’ of a protein called TDP43, which is known to occur within the cells of people with MND.
Previous drugs we have tested
Memantine
The first drug, memantine, is already used to improve the memory of people with Alzheimer’s disease (a form of dementia) by reducing the action of a brain chemical called glutamate. Previous trials have tested memantine on people with MND but not in large enough numbers to provide any conclusive evidence as to the effects of the drug. These previous trials showed some evidence of functional improvement and the drug caused no notable side effects. Investigators also reported slowing of spinal motor neuron loss so it is thought that this drug may slow the damage to neurons in people with MND.
Trazodone
The second drug, trazodone, is used widely in the treatment of anxiety and depression. It has been shown to protect neurons in animal studies by slowing production of faulty proteins that can cause neurons to die. Trazodone has been tested in other neurological conditions including Parkinson’s disease, Alzheimer’s disease and frontotemporal dementia and no notable side effects were seen. In trial participants with frontotemporal dementia investigators also observed improved cognition.
Drug selection
To select drugs for this trial, our scientists use an unbiased system to review all published research studies in MND and other neurodegenerative diseases and produced a list of drugs that may slow progression of MND. We look at studies in other neurodegenerative diseases alongside MND studies, because neurons may be affected in a similar way across different diseases. We produce a shortlist of drugs based on how well the studies were conducted, and how effective and safe the drugs were shown to be.
We also look at the results of laboratory studies, in which we test drugs on human brain cells which we grow in a dish from stem cells donated by people with MND.
A group of consultant neurologists then reviews the shortlisted drugs and decides which are most likely to slow progression of MND, alongside being safe to be taken by people living with the disease.
Selecting more drugs for trial
MND-SMART is designed to run continuously for years to come to test treatments that may slow, stop or reverse the progression of MND.
To help select future drugs we will trial, we are continually repeating the process of reviewing published information from MND and neurodegenerative disease studies to make sure we are examining the latest evidence.
