Friedreich ataxia (FRDA) is a rare hereditary neurodegenerative disease characterized by progressive ataxia and cardiomyopathy. The cause of the disease is a defect in mitochondrial frataxin, an iron chaperone involved in the maturation of Fe-S cluster proteins.

Read More: Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases and severe loss of mitochondrial Fe-S proteins.

BACKGROUND:
Friedreich's ataxia is an autosomal recessive neurodegenerative disease where impaired mitochondrial function and excessive production of free radicals play a central pathogenetic role. Idebenone, a synthetic analogue of coenzyme Q, is a powerful antioxidant that was first administrated to Friedreich's ataxia patients less than 10 years ago.

OBJECTIVE:
The aim of this study was to evaluate the efficacy of idebenone administration and define the optimal dosage.

Read More: Idebenone in Friedreich's ataxia

The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The ¹⁸F-radiolabeled polyamides were prepared by oxime ligation between 4-[¹⁸F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus.

Read More: In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography

Deficiency in the nuclear-encoded mitochondrial protein frataxin causes Friedreich ataxia (FRDA), a progressive neurodegenerative disorder associating spinocerebellar ataxia and cardiomyopathy. Although the exact function of frataxin is still a matter of debate, it is widely accepted that frataxin is a mitochondrial iron chaperone involved in iron-sulfur cluster and heme biosynthesis. Frataxin is synthesized as a precursor polypeptide, directed to the mitochondrial matrix where it is proteolytically cleaved by the mitochondrial processing peptidase to the mature form via a processing intermediate.

Read More: The in vivo mitochondrial two-step maturation of human frataxin