A protein found in blood plasma could be a biomarker for ALS

The discovery of a potential protein marker for amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease, could help detect and monitor the progression of this degenerative disorder¹.

ALS, also known as Lou Gehring's Disease, is a progressive neurodegenerative disorder characterised by the death of motor neurons in the brain and spinal cord. This cell death leads to a gradual loss of muscle control, and usually results in death by respiratory failure within a decade of diagnosis.

Although the causes of ALS are still unknown, a large number of genetic mutations in at least 10 different genes linked to the disease have been identified. Some of the mutations are located within the gene encoding a small protein called angiogenin. Mutations in the angiogenin gene account for up to 1% of ALS cases.

Angiogenin performs multiple functions. It is a potent stimulator of blood vessel formation, but is also known to have neuroprotective properties. It also induces the formation of stress granules and can degrade RNAs.

To investigate the possible role of angiogenin in ALS, Maria Ivanova, of the Research Center for Neurology in Moscow, and her colleagues, took blood samples and cerebrospinal fluid from 30 ALS patients and 26 matched healthy volunteers. From the blood plasma they also isolated tiny spherical structures called exosomes, which are found in the spaces surrounding cells and are important in cell-to-cell communication—they may also play a role in transporting angiogenin.

Working in collaboration with researchers at the National Research Center for Epidemiology and Microbiology, the team measured angiogenin concentrations in all the samples, and found that it was present at significantly lower levels both in the plasma and exosome fractions of ALS patients compared to those isolated from the healthy controls.

Furthermore, in the ALS patients, the concentration of angiogenin was related to disease severity, with those having better muscle control exhibiting higher levels of the protein.

The researchers also used electron microscopy to examine and compare the size and structure of exomes isolated from the ALS patients and controls, but did not find any differences between them.

The results, published recently in the Neurochemical Journal, suggest that angiogenin levels in blood plasma and exosomes may be a biological marker for ALS, with concentrations of the protein gradually decreasing as the disease progresses, although the finding needs to be confirmed in larger-scale trials.

“Now we are investigating angiogenin as a potential treatment option with a study on its protective effect in an animal model of ALS,” says Ivanova.