Imaging Technique Measures Mitochondrial Abnormalities in ALS

An imaging technique, called 31-phosphorus magnetic resonance spectroscopy (MRS), can be used to assess mitochondrial abnormalities in people with amyotrophic lateral sclerosis (ALS), a new study demonstrates.

This non-invasive procedure could be useful for evaluating potential ALS treatments, researchers suggested.

The study, “Magnetic resonance spectroscopy reveals mitochondrial dysfunction in amyotrophic lateral sclerosis,” was published in the journal Brain.

One of the characteristic biological features of ALS is the abnormal function of mitochondria — cellular compartments that play a major role in energy production, in addition to other important biological functions.

Although the causes of ALS are not understood completely, mitochondrial abnormalities are believed to be important in development of the disease. However, there has been little research in living people with ALS to support this idea.

Now, researchers from the University of Sheffield in England used MRS to measure mitochondrial activity in 20 ALS patients and in 10 healthy control subjects. Broadly, MRS allows researchers to measure levels of mitochondria-associated molecules, such as adenosine triphosphate (ATP), which is the “energy currency” primarily used by cells.

“Whilst cranial [MRS] has been applied to identify disease-specific bioenergetic [mitochondria-associated] changes in anatomically relevant regions in Alzheimer’s, Parkinson’s, and Huntington’s diseases, this is the first study in ALS,” the researchers wrote.

By comparing measurements taken in patients and controls, the researchers were able to identify signs of mitochondrial abnormalities both in the brain and muscle of ALS patients. The exact type of differences varied in the different tissues.

“We found that phosphocreatine levels were depleted in the brain compared to healthy controls and, in the muscle, we found that inorganic phosphates were elevated in patients with [ALS]. Both of these findings are consistent with mitochondrial dysfunction occurring in these people,” study co-author Matilde Sassani, PhD, said in a press release.

Additionally, in both brain and muscle tissue of ALS patients, cells could do less work with the same amount of ATP, which is again indicative of mitochondrial problems, according to the researchers.

Other differences, such as increased pH (greater acidity) in muscles — also indicative of mitochondrial abnormalities — also were noted.

Although the small sample size of this study makes it difficult to draw broad conclusions, findings suggest these measurements of mitochondrial problems are relevant in a clinical sense. For example, ALS patients with lower levels of phosphocreatine in their brain tissue were more likely to report greater disability, as assessed by the revised ALS functional rating scale, and worse lung function.

“Replication of our findings in a larger longitudinal study is necessary to determine whether the identified changes are sensitive to disease progression and so act as a marker of target engagement for future therapeutic agents,” the researchers wrote.

“Nonetheless, this study provides an important first demonstration that [mitochondrial] dysfunction is detectable [in living individuals] even in small cohorts of ALS patients and appears clinically important,” they added.

The researchers suggested that measuring mitochondrial problems through MRS could be important for determining whether investigational ALS treatments are effective.

“Treatments that aim to rescue mitochondrial function in [ALS] are being investigated in labs around the world,” said co-author Thomas Jenkins, PhD, senior clinical lecturer at the Sheffield Institute for Translational Neuroscience. “This non-invasive tool can demonstrate whether medications in development are successfully targeting mitochondria, which is an important step in selecting treatments to take through to clinical trials.”