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The synthesis of minds and molecules leads to potential therapy for pantothenate kinase-associated neurodegeneration

Andrea H. Németh
DOI: http://dx.doi.org/10.1093/brain/awt351 8-11 First published online: 13 January 2014

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by mutations in the mitochondrial enzyme pantothenate kinase 2 (PANK2). In this issue of Brain Brunetti et al. (2014) report the use of a ketogenic diet in a mouse knock-out of PANK2 to more accurately model the human disease and further show that feeding with pantethine may be a possible treatment strategy for PKAN in humans.

The history of our understanding of PKAN is fascinating, but has grim beginnings. In 1922, Julius Hallervorden and Hugo Spatz, two eminent neuropathologists, described the clinical condition that subsequently bore their name, as well as the neuropathological hallmark of PKAN: iron deposition in the globus pallidus and substantia nigra (zona reticularis). However, in the following years both actively participated in Nazi euthanasia programmes while working at the Kaiser Wilhelm Institute for Brain Research (Zeidman and Pandey, 2012). Although these shameful activities were reported shortly after the end of World War II the medical community was not widely aware of them until 1992, when concerted attempts were made to replace the eponym Hallervorden-Spatz syndrome with a more suitable and respectful alternative (Shevell, 2012).

More recent work on PKAN has been elegant and impressive, particularly studies from the laboratory of Susan Hayflick, where the gene was located to chromosome 20p (Taylor et al., 1996) and the term ‘neurodegeneration with brain iron accumulation type 1’ (NBIA1) was proposed. When mutations were identified in PANK2 the term PKAN was suggested instead (Zhou et al., 2001) and this was quickly followed by comprehensive paper delineating the clinical, radiological and imaging findings in a series of genetically characterized patients (Hayflick et al., 2003). PKAN turns out to be one of a family of NBIAs and has led to an emergence of studies aimed at elucidating the …

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