Researchers have been trying for years to better understand the mutations which cause the rare disorder called Charcot-Marie-Tooth disease (CMT). Tremendous progress has been made. But now that we know more about the mutations themselves, we must uncover the nuances of their consequences for patients.

The Research

There are two primary ways to study disease. Researchers can either use an animal model of the disease, or study cells carrying the disease in a laboratory dish. The latter form of research is called an in-vitro investigation.

Animal models can be difficult to implement logistically and because of ethical concerns. The problem with in-vitro studies is that in order to be effective, the right cells have to be used, and in order to be used, they must be accessible.

For CMT research, nerve cells, like spinal motor neurons, are utilized. These cells are responsible for communicating from someone’s brain to their muscles. Studying spinal motor neurons directly from a patient is not possible. But researchers can use something called hiPSCs, or human induced pluripotent stem cells, as an alternative. These cells can be generated from a patients skin cells or blood cells, and then transformed into different cell types for the sake of research.

Scientists have come up with a new protocol to use these cells to generate spinal motor neurons of CMT. With this type of model, researchers will better be able to study the disease, understand its response to therapies, and gain increased understanding of how it functions.

This study was recently published in the journal Brain Sciences.

How it Works

To generate the spinal motor neurons, researchers first must collect either skin or blood cells from a patient. Then, they use these cells to form the hiPSCs. The newly generated hiPSCs are then differentiated into the spinal motor neurons.

The huge advantage of this method is that because the cells come directly from a patient, they possess the exact same genetic mutations as the patient.

If you’re up to date on this topic you may be asking- hasn’t this been done before? Yes. There have been multiple different protocols developed for this process. However, the motor neurons that are generated are too often inefficient or ineffective in diseases such as CMT.

These researchers investigated their new protocol in patients with CMT type 2 as well as five individuals who did not have a CMT diagnosis.

They first used one of the previous protocols. They found it possible to obtain the motor neuron cells for both groups, but it was a more difficult process for the CMT2 patients. The team continued to try a few other old protocols.

Through trial and error with continued evaluations of growth factors and timing, the team found a protocol which had a 80% success rate. This protocol can generate the needed cells in 20 days.

The hope is that with better research they will develop a greater knowledge of this disease. If we better understand the molecular pathways involved, we may be able to develop new and better therapies for CMT patients.

You can read more about this investigation here.