Key to Possibly Reversing Friedreich’s Ataxia Found


By Danielle Bradshaw from In The Cloud Copy

A Tufts University science team was able to identify a means to possibly reverse Friedreich’s ataxia. Friedreich’s ataxia (also known as spinocerebellar degeneration) is a rare genetic disorder whose symptoms include the sensation loss in the arms; impaired speech, hearing, and vision; and difficulties with walking. Other symptoms included damage to the heart, brain, and spinal cord. About 1 in every 40,000 people in the United States have Friedreich’s ataxia and although there is no cure, the aforementioned Tufts science team has found a molecular mechanism that could nullify what causes it.

Friedreich’s ataxia is the result of an expanded version of a three-letter genetic sequence (GAA) inside of the FXN gene. Inside of this particular gene is where frataxin is made, which is needed to ensure that the mitochondria within the body’s cells are able to function properly.

In a healthy person, there would be 8 to 34 repeated GAA sequences, but people that have Friedreich’s ataxia can possess anywhere from 35 to 70. This overly-repeated sequence makes it hard for the body’s cells to properly process FXN and in turn causes difficulties in creating the frataxin that the mitochondria require to power cells. As a result, this causes the body’s cells to function improperly.

The argument could be made that the constant repeats of DNA sequences bring the body to a shuddering halt. They may also result in other kinds of mutations that could impact DNA around the defective portion and can cause chromosomes to become “brittle” and break apart or outright rearrange themselves. The biology department of Tufts University has found that the ability to shrink the repeated DNA to match the amount found in unaffected people could possibly make the DNA of the affected patients stable and alleviate the disease’s symptoms.

It’s well known by many researchers at this point that the GAA repetitions expand and contract constantly due to their instability. What this research at Tufts University accomplished is finding what happens when GAA repetitions contract and how this could possibly help patients with Friedreich’s ataxia.

In order to actually find the mechanism that creates the repeats, those behind the study conducted an experiment with yeast (Saccharomyces cerevisiae, specifically) to measure how the different ways of interrupting the repeated DNA contractions affected the yeast. They found out the contractions occurred during what is called the “lagging strand synthesis” – the moment when two DNA strands are copied and one does so continuously while the other one (the lagging strand) is put together with tiny, poorly “fastened together” parts.

The researchers saw that the repetition’s contractions relied on whether or not the DNA repeats in the form of a rare triple-helix structure across the lagging strand as opposed to the typical double-helix. In normal cases, the replication function travels along the lagging strand but isn’t able to get across the triple-helix formed by the repeating sequences. It was observed, however, that when the replication function was able to bypass it, the cloned strand of DNA had fewer GAA repetitions.

While it’s true that the findings were reached by experimenting with yeast, they still offer a great amount of insight into what it is that makes the repeated DNA unstable inside of patients with Friedreich’s ataxia. There are hopes that the study can eventually lead to treatments that help decrease the amount of replicated DNA sequences in patients that suffer from this illness.

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