Altered Cellular Metabolism in Friedreich’s Ataxia Is Potential Therapeutic Target, Review Says

Alice Melão avatar

by Alice Melão |

Share this article:

Share article via email
Friedreich's diagnosis confusion

Recent research in Friedreich’s ataxia (FA) has revealed new possibilities for lipid metabolism as a therapeutic target to slow the progression of the disease in patients.

The latest knowledge of the molecular basis of FA and its underlying metabolic alterations was discussed in a review study titled “Oxidative stress and altered lipid metabolism in Friedreich ataxia,” published in the scientific journal Free Radical Biology and Medicine.

Friedreich’s ataxia is caused by a mutation in the gene for the mitochondrial protein frataxin. The mutation leads to a deficiency in the frataxin protein, with major impacts on cellular metabolism.

The frataxin deficiency mainly affects the heart and the nerve cells (called neurons) of the brain and spinal cord, the peripheral nerves, and the insulin-producing cells. The three major symptoms of the disease are ataxia, cardiomyopathy (diseases of the heart muscle), and diabetes.

The role of the frataxin protein is still not entirely clear, although it appears to act as a storage area for iron, releasing it when needed. But when frataxin is missing or flawed, iron appears to build up in mitochondria, which affects mitochondria metabolism and the protection of cells against oxidative stress damage.

This review summarizes the importance of frataxin activity in the cellular metabolism of Friedreich’s ataxia disease progression.

Lipids are the buildings blocks that make up the structure of living cells. They contain fats, natural oils, waxes, hormones, vitamins and more. Lipid metabolism has not historically been considered an important factor in FA. Previous studies have reported lipid metabolism alterations in experimental models and also in FA patients.

The authors of this review highlight the relevance of lipid metabolism disturbance as a consequence of mitochondrial dysfunction in the disease progression, and explore its relationship with insulin resistance in Friedreich’s ataxia.

Finally, the authors focus on therapeutic strategies that are either used in different parts of the world (not approved to treat FA in the U.S.) or are in development which specifically target the disrupted metabolic mechanism found in FA, such as:

  • Idebenone (Canadian brand name Catena), an antioxidant used to target oxidative stress;
  • Vincerinone, a last-generation antioxidant drug that targets oxidative stress as well as improves mitochondrial metabolism;
  • Actos (pioglitazone, an anti-diabetic drug not approved to treat FA), used to target lipid metabolism and oxidative stress responses, also with the capability to improve frataxin expression;
  • Carnitor (levocarnitine), used to improve lipid and mitochondrial metabolism.

“Lipid metabolism is compromised in FA and therefore is emerging as a new potential therapeutic target. Current approaches are also meant to restore mitochondrial function, improve energy metabolism and decrease oxidative stress,” the authors wrote.

Future and ongoing studies may uncover the real potential of these therapeutic strategies to alleviate the progression of Friedreich’s ataxia.