In the last decade, new instruments have been used to study ALS patients very carefully. These studies have led to the identification of biomarkers such as proteins that are in the blood and brain fluids that can be used to predict disease progression. Sometimes we can use such methods to distinguish ALS patients that have different underlying causes.

Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation (TMS) is a magnetic method used to stimulate small regions of the brain. During a TMS procedure, a magnetic field generator, or "coil," is placed near the head of the person receiving the treatment. By creating a small magnetic pulse, the motor regions in the brain can be activated. Normally, after such a pulse, the motor region cannot be activated easily again shortly after because of an inhibition system which prevents seizures in the brain. In ALS patients this inhibition system is not functioning well which leads to a hyperactive brain and spinal cord. This hyperactivity causes ALS patients to progress fast in the disease, and it can be quantified precisely using TMS. QurAlis uses TMS to identify patients that have a hyperactive brain so that we can treat these patients specifically. We also use TMS to help us develop the right medicine and to measure the effects of our treatment. 

Transcranial Magnetic Stimulation (TMS)

Geevasinga, N., et al., Pathophysiological and diagnostic implications of cortical dysfunction in ALS. Nat Rev Neurol, 2016. 12(11): p. 651-661.

Nerve Threshold Tracking

Threshold tracking techniques measure nerve excitability in the forearms of ALS patients by introducing small currents. The excitability depends on the nerve properties at the site of stimulation. In ALS patients the motor nerves are hyperexcitable, and the more hyperexcitable the nerves are, the faster the disease progresses. From laboratory experiments, we know that hyperactivity leads to the loss of nerves. It is therefore important to develop drugs that bring the excitability of these nerves back to normal levels. Our founders have identified an epilepsy drug (Ezogabine/retigabine) that has does exactly this. This drug is now tested in a large clinical trial in the United States.

Proteins in the Cerebral Spinal Fluid (CSF)

Around the brain and spinal cord is a fluid which acts as a cushion or buffer which is called the cerebrospinal fluid (CSF). There is about 125-150mL of CSF at any one time, and it provides basic mechanical and immunological protection to both brain and spinal cord. There are proteins which are actively secreted into the CSF to help with its function or to remove them from cells. Unfortunately, some of these proteins are harmful to other cells that get in contact with the CSF. We can measure the levels of proteins in the CSF by taking small samples from ALS patients. By doing this, we can find information that helps a doctor determine if a patient has ALS and what type of ALS. We can also use these measurements to determine if certain therapies have an effect. In certain ALS patients, toxic proteins (dipeptide repeat proteins) are produced by cells with a mutation in the C9orf72 gene and these proteins are building up in the CSF. From there these toxic proteins are taken up by neurons that degenerate in ALS. These proteins are very toxic to neurons. QurAlis is developing a device that clears these proteins from the CSF.

Blood Biomarkers

The development and progression of ALS can partly be determined by measuring levels of proteins and cells in the blood. There is a barrier that separates the blood from the brain and spinal cord, called the “Blood-Brain Barrier.” Because ALS is a disease in the nervous system, we have to be careful with the interpretation of the results. Nonetheless, because it is relatively easy to extract blood from ALS patients, it provides a powerful tool to further our understanding of the disease and to measure the effects of potential therapeutics.   


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