Disease biomarkers in a SOD-G93A mouse model of amyotrophic lateral sclerosis and their translational potential in human disease

Description:

What this research means to you: Diagnosis of MND is currently a very lengthy process because of the lack of a definitive diagnostic test. In addition, doctors and researchers have no accurate, objective way of measuring disease progression or the effects of potential treatments during clinical trials. This project aims to explore the feasibility of developing a simple blood test to aid diagnosis and disease monitoring. The researchers will investigate substances found in the blood that could be indicative of the presence of MND and how the levels of these substances change to reflect the progression of the disease.

The researcher explains in more detail: During the initial part of our investigation, we will take blood samples from mice that model MND at regular intervals as their disease progresses and measure how a variety of substances in the blood change over time - previous work has suggested that these substances may be altered in MND. We will correlate any changes with loss of muscle strength and motor neurone degeneration in the mice. We will then investigate how levels of the substances change when the mice are treated with an experimental drug called Arimoclomol, which is known to slow disease progression in this animal model and is currently undergoing clinical trials in people with MND. This work will indicate whether a particular substance or combination of substances can reflect the progression of the disease and the response to a treatment, thus functioning as a “biomarker”.

We will then go on to check whether the potential markers we have found are an accurate indicator of MND in human patients. We will collect blood from all 100 participants at 3 month intervals from diagnosis onwards and compare changes in our potential markers with those seen in the blood from healthy volunteers and people who have suffered spinal cord damage. Cerebrospinal fluid (which bathes the brain and spinal cord) will also be collected from at least 25 participants with MND.

Ultimately, this work aims to establish the validity of a marker or markers that could be used routinely and simply as a diagnostic test and to assess progression of MND. The discovery of markers can also offer a valuable insight into disease mechanisms.