A manmade version of the frataxin protein that’s missing in Friedreich’s ataxia increased frataxin levels in the muscles of mice with the disease, increasing their survival, a study found.
Scientists used parts of several proteins to create what they called a fusion version of frataxin.
The team reported its findings in the Journal of Cellular and Molecular Medicine. The article is titled “Frataxin-deficient neurons and mice models of Friedreich ataxia are improved by TAT-MTScs-FXN treatment.”
Friedreich’s ataxia is an inherited disease that stems from the body inserting an extra DNA sequence in the FXN gene. The insertion prevents the gene from producing frataxin, a deficiency that leads to FA.
Frataxin can be found throughout the body, but normally occurs at higher levels in the heart, muscles, spinal cord, liver, and pancreas. Although its role is not fully understood, scientists do know that it plays a key role in the normal functioning of mitochondria, cell components that generate energy.
Lack of frataxin leads to impaired mitochondria activity and reduced energy production. In the absence of energy, cells cannot work properly, and some may sustain damage. This helps explain why people with FA often experience muscle weakness, heart disease, and diabetes.
To treat FA, scientists have been working on ways to force the production of frataxin or deliver it to tissues where it’s needed. This has led to the development of such therapies as Chondrial’s CTI-1601 and Voyager’s VY-FXN01.
But so far such strategies have either failed or have yet to go through a full clinical trial program and be approved.
An international team of researchers decided to test a new formulation of engineered frataxin as a potential treatment for FA.
They fused a small protein sequence known as TAT with a sequence called MTScs and a full frataxin sequence. Each component has a specific role to play in delivering the protein to where it’s needed and in making sure it acts like naturally occurring frataxin.
The TAT sequence merges with a cell’s membrane, allowing the engineered protein to go inside the cell. The MTScs sequence ensures that the protein integrates into mitochondria the way it’s supposed to.
A previous study showed that a fusion TAT-MTScs-FXN protein could deliver frataxin into the mitochondria of cells from both lymphoma and FA patients that scientists grew in a lab.
In the latest study, researchers confirmed that the TAT-MTScs-FXN protein was able to penetrate nerve cells and reach their mitochondria. The higher levels of frataxin that ended up in these cells prevented the nerve damage that is a hallmark of FA.
The team then administrated the fusion protein to two mouse models of FA. As with the lab-grown cells, the engineered protein was able to reach the mitochondria of muscle cells, restoring their activity. This led to the mice living longer than untreated control mice, the team said.
Overall, the researchers concluded that “the results obtained with both cell and animal models indicate that this approach can be a promising strategy for FA treatment.”