Cancer Treatment May Be Able to Prevent Heart Problems in Friedreich’s Ataxia, Study Suggests

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by Alice Melão |

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A therapy already approved to treat cancer could potentially be used to prevent heart abnormalities in Friedreich’s ataxia patients, according to a study that used a fruit fly model of the disease.

The study, “Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich’s ataxia,” appeared in the journal Disease Models & Mechanisms.

Friedreich’s ataxia is caused by a genetic defect in the FXN gene that leads to reduced levels and partial loss of function of the protein frataxin, for which the gene provides instructions.

Although the role of frataxin in cells is still not fully understood, it is known that the protein is important for normal mitochondrial activity and consequently for the production of energy.

Lack of frataxin causes cells to accumulate toxic oxidant oxygen molecules and reduces the energy cells require to support their normal function and basic needs.

Researchers have tried to find therapeutic compounds that can help reduce oxidative stress in cells or improve frataxin levels. However, the strategies attempted so far have failed to achieve an effective solution.

A team at the Université Paris Diderot in France tested the potential of 1,280 approved therapies to prevent heart abnormalities, a life-threatening complication of Friedreich’s ataxia.

To test the therapies, researchers used fruit flies genetically engineered to lack frataxin in the heart. This model of the disease mimics some of the cardiac symptoms of the human disease, including an enlarged heart, impaired contractility, and thicker heart walls.

“To our knowledge, this is the first pharmacological screening of this extent performed in vivo on an animal model of cardiac disease and at the adult stage,” the researchers wrote.

After treating the flies with all the approved treatments, the researchers were able to identify 11 that could reduce heart dilatation, and five that made frataxin-mediated heart symptoms worse.

Paclitaxel, also known by its brand name Taxol, showed the strongest protective effect on cardiac dilatation.

Flies treated with this therapy had a reduction of about 47% in diastolic heart size — which corresponds to the largest cardiac dimension — compared with untreated insects. This represented an increase in index dilation of only 42% compared with healthy flies.

Paclitaxel is a chemotherapeutic medicine commonly used to fight cancers by preventing malignant cells from dividing, ultimately leading to the death of these cells. It works by stabilizing structural elements of cells known as microtubules. These are required for maintaining cells’ normal structure and are also required for normal cell division.

Treatment with this particular medication prevented heart dilation in the Friedreich’s ataxia fly model, a response that was enhanced with higher doses. Paclitaxel was also particularly efficient in improving heart contractility with a response similar to that of healthy flies.

Among the other 10 identified compounds were therapies that have already been shown to have positive effects on the cardiovascular system and anti-inflammatory properties.

The anti-inflammatory therapy Azulfidine (sulfasalazine) and the antidepressant Luvox (fluvoxamine) were two such compounds researchers believe could be of interest for future investigations, especially considering prior studies in Friedreich’s ataxia have already revealed some potential benefits.

“This study may lead in the future to therapeutic applications and improves our knowledge of the mechanisms involved in cardiac dysfunction associated with Friedreich’s ataxia,” the researchers said.