Study probes gene responsible for neuromuscular disorder

Peterborough, ON – Craig Brunetti, a biology professor at Trent University, along with environmental and life sciences PhD student Andressa Lacerda and undergraduate biochemistry student Emily Hartjes, have discovered the cellular mechanism that results in Charcot Marie Tooth (CMT) disease, the most common neurodegenerative disease in humans. CMT is a disease that causes damage to the peripheral nerves of the arms and legs and eventually leads to muscle weakness and reduced mobility. The researchers’ discovery, published on July 24, 2014 in the scientific journal PLoS ONE, will lead to a better understanding of the disease, and provide clues for developing better diagnoses and treatments.

The research, undertaken by Ms. Lacerda with support from Dr. Brunetti and Ms. Hartjes, focuses on LITAF, a cellular gene that is used by the body to degrade and dispose of proteins. If proteins in the body aren’t properly broken down, old protein fragments can accumulate and damage cells. The inability to break down proteins has been linked to a number of neurological disorders.

Until now, little in-depth research had been done on the LITAF gene. Mutations in the LITAF gene have been found in a subset of patients with CMT. LITAF is normally found in one part of the cell called the lysosome, which is responsible for breaking down proteins. In the published paper, the Trent researchers explain that mutations that result in the development of CMT cause LITAF to shift from the lysosome to another cellular compartment, the mitochondria. Changing the location of LITAF in the cell results in an inability of LITAF to carry out its proper function in the cell resulting in disease.

These new findings could have far-reaching effects on the diagnosis and treatment of Charcot Marie Tooth Disease, which affects 1 out of every 2,500 people. For example, Ms. Lacerda’s work demonstrated that while some mutations in LITAF completely change the location of LITAF in the cell, other mutations result in only a partial change of LITAF. This may lead to different clinical outcomes for patients depending on the type of LITAF mutation that they carry. Future research could link different mutations in the LITAF gene with different types of CMT, and therefore, to develop new forms of therapy targeted to each type of mutation.

Ms. Lacerda began her research on the LITAF gene in 2011. “It was very interesting for me because, for a while, I was the only one at Trent doing this type of research on human-related diseases at the cellular level,” she said. “It’s very exciting for me to finally see all this work in one paper, and to have this work coming out of Trent.”

This groundbreaking discovery was the result of open-minded study: originally, Prof. Brunetti and his team intended to explore how LITAF affects viral replication, but in order to understand this impact, they began to research the gene itself. Prof. Brunetti considers this unexpected path to be a perfect example of the value of basic research. “I’ve always approached science as being very fluid,” he said. “In moving from one research area to another, in essence you’re using the same tools, but you’re not tied to specific questions. When you have the tools and the techniques, you can apply them to a large range of disciplines as long as you ask the right questions.”

Future research in the lab is now focused on exploring the role of LITAF in other forms of CMT.  In addition, the lab has found evidence that the LITAF gene could also be involved in the body’s immune response to viral pathogens, which may be a promising area for further study within Prof. Brunetti’s work on viruses and the immune system.