Our cells require proteins, which are composed of individual amino acids connected in a long chain, to perform important functions. These amino acids are delivered to protein-building machinery by another molecule called a tRNA. Amino acids and tRNAs are attached together, or charged, by an enzyme colloquially known as ARS.
Mutations in ARS enzymes cause diseases such as Charcot-Marie-Tooth disease, which affects the nerves to a person's arms and legs, because cells cannot make proteins properly. Currently, there are few treatments for ARS defects. However, researchers predict that flooding cells with extra amino acid might allow defective ARS enzymes to function better.
To test this, scientists identified patients with ARS mutations that cause charging defects, and grew their cells in a petri dish. They then treated these cells with different amounts of amino acid, and compared the electrical impedance of the cells that received treatment to those that did not. “Impedance analysis” is an approach where scientists put cells on a surface that can conduct electricity. As cells grow, they block the electrical current, and the speed at which the current is blocked corresponds to how fast the cells are growing.
The scientists found cells with ARS mutations that were treated with amino acids grew faster than cells that did not receive treatment. These promising results meant that the researchers could move on to trying this treatment in the patients themselves. They designed specific amino acid treatments for four people with the same ARS mutations they studied in cells, monitored their symptoms over time, and found that giving patients amino acids alleviated many of their most severe symptoms.
While we still don’t know if these results are applicable to all patients with ARS mutations, this study found a potential new way to treat ARS mutations in patients. Considering that ARS mutations can cause very severe disease, this is exciting and promising for both scientists and patients alike.