Researchers Create Worm Model to Expand CMTX6 Research

In medical research, researchers often use a variety of non-human models to expand their understanding of various diseases or potential treatments. For example, mice models, or non-human primates, are frequently used. According to Charcot-Marie-Tooth News, Australian researchers and scientists recently developed a new animal model to further their understanding of X-linked Charcot-Marie-Tooth disease type 6 (CMTX6). Which animal? A worm. Take a look at the full research findings published in Human Molecular Genetics.

Charcot-Marie-Tooth Disease (CMT)

To begin, it’s first important to get an understanding of what Charcot-Marie-Tooth disease (CMT), or hereditary motor and sensory neuropathy, actually is. Although CMT is considered rare, it is also one of the most commonly inherited neurological disorders. There are multiple forms of CMT, which all depend on the specific associated genetic mutations. For example, PDK3 gene mutations cause CMTX6. Altogether, there are 90+ genetic mutations associated with CMT. In each case, the mutations affect the peripheral nerves. While some forms of CMT affect males and females equally, CMTX6 is X-linked. This means that females are often asymptomatic or have only mild symptoms, while males will present with more severe symptoms. Learn more about CMTX6.

Often, patients with CMT begin experiencing symptoms in adolescence or early adulthood, though symptoms may also appear later in life. Symptoms include:

  • Difficulty walking
  • Muscle atrophy and weakness in the hands
  • Lower leg and foot deformities
  • Foot drop
  • Frequent tripping
  • Muscle weakness in the lower extremities
  • Difficulty with fine motor skills
  • Tremor
  • Numbness, tingling, or burning in the hands and feet

CMTX6 Worm Models

Within this study, researchers sought to better understand the p.R158H PDK3 mutation. To do so, they decided to create an animal model of CMTX6 to better understand the effects of the mutation. So they created an eelworm model of CMTX6. Interestingly, this is actually the first-ever animal model of this condition.

To begin, researchers first genetically engineered the eelworms so that they would have these specific mutations. The researchers engineered some worms to have more of the mutated gene, while others had the mutation only affect GABAergic motor neurons, which play a role in movement. Next, researchers proceeded to perform various tests and biological evaluations on the worms. Findings included:

  • For the worms whose mutation only affected, or was produced by, GABAergic motor neurons, nerve cell death and movement abnormalities occurred.
  • Alternately, for those with the mutation affecting each cell, the worms experienced synaptic abnormalities, a smaller body width, a higher risk of oxidative stress, and changes in energy metabolism.

Ultimately, researchers saw that the mutations caused, in the worm models, the same symptoms associated with CMTX6. As research moves forward, these models can now be used to better explore and understand this condition, while also providing a platform for drug screening or testing.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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