Gene therapy that could restore mitochondrial function and alleviate neuronal impairment in peroxisomal biogenesis disorders.

Peroxisomal biogenesis disorders (PBDs), such as rhizolmelic and phizolmelic chondrodysplasia puncata, are a set of rare inherited diseases caused by defects in the peroxisomes. Children with these disorders often present with dysmorphia in the face and head, along with malformations of the brain, eye, and kidney. There is currently no cure for PBDs, with treatment options being limited to symptomatic therapies.

University of Utah researchers have developed a potential gene therapy for PBDs. When peroxisomes are absent or malfunction, peroxins accumulate in the outer mitochondrial membrane, causing respiration defects and affecting mitochondrial amino acid metabolism. The proposed therapy overexpresses of a member of the mitochondrial quality control system to remove accumulating peroxins, restoring respiration and amino acid metabolism and potentially treating the cause of PBDs

Concept

• Potential to be the only curative treatment available for PBDs.
• Could reduce neuronal impairment in PBDs and related disorders.
• Potential candidate for orphan drug designation.

Exploiting Mitochondrial Quality Control Mechanisms to Find Alternative Therapies in Peroxisomal Biogenesis Disorders. Poster available upon request.

Nuebel E, Morgan J, Fogarty S, et al. (2021). The biochemical basis of mitochondrial dysfunction in Zellweger Spectrum Disorder. EMBO Reports. 22:e51991. https://doi.org/10.15252/embr.202051991

Jason Young
(801) 587-0519
jason.r.young@utah.edu