First published February 3, 2014 - More info
Degeneration of peripheral motor axons is a common feature of several debilitating diseases including complicated forms of hereditary spastic paraplegia. One such form is caused by loss of the mitochondrial energy-dependent protease paraplegin. Paraplegin-deficient mice display a progressive degeneration in several axonal tracts, characterized by the accumulation of morphological abnormal mitochondria. We show that adenoassociated virus–mediated (AAV-mediated) intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice. One single injection before onset of symptoms improved the motor performance of paraplegin-deficient mice for up to 10 months, indicating that the peripheral neuropathy contributes to the clinical phenotype. This study provides a proof of principle that gene transfer may be an effective therapeutic option for patients with paraplegin deficiency and demonstrates that AAV vectors can be successfully employed for retrograde delivery of an intracellular protein to spinal motor neurons, opening new perspectives for several hereditary axonal neuropathies of the peripheral nerves.
Marinella Pirozzi, Angelo Quattrini, Gennaro Andolfi, Giorgia Dina, Maria Chiara Malaguti, Alberto Auricchio, Elena I. Rugarli
Original citation: J. Clin. Invest. 2006;116(1):202–208. doi:10.1172/JCI26210.
Citation for this corrigendum: J. Clin. Invest. 2014;124(2):871. doi:10.1172/JCI75082.
During the assembly of Figure 3, A and B, of this manuscript, bands from the paraplegin immunoblot were cut out and placed on a blank background to eliminate background signal. The original, unadjusted paraplegin blots are shown in the corrected figure panels below. Arrows indicate the paraplegin bands. The findings are consistent with the original publication, and the interpretation of the results remains the same.
The authors regret the error.