Summary
Hallervorden–Spatz syndrome (HSS) is a devastating neurological disease, characterized by iron accumulation in the globus pallidus in the basal ganglia. Most HSS cases are caused by mutations in one of the four human pantothenate kinases (PANK2). This PANK2-caused subgroup of HSS is sometimes referred as PKAN (pantothenate-kinase-associated neurodegeneration). No effective treatment for PKAN or HSS is currently available. fumble, a Drosophila mutant that carries a mutation in Drosophila Pank, has many features similar to those of PKAN patients. In this study, we used fumble as a model to evaluate various compounds or nutritional products for their possible therapeutic efficacy. While no product was found to dramatically improve the symptoms, GKE (containing Ginkgo biloba extract and flavone) and vitamin E showed statistically significant beneficial effects. Our studies indicate that pantothenate is of limited value in alleviating fumble phenotypes and also suggest that some compounds might have deleterious effects.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Afshar K, Gonczy P, DiNardo S, Wasserman SA (2001) fumble encodes a pantothenate kinase homolog required for proper mitosis and meiosis in Drosophila melanogaster. Genetics 157: 1267–1276.
Ching KH, Westaway SK, Gitschier J, Higgins JJ, Hayflick SJ (2002) HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. Neurology 58: 1673–1674.
Hayflick SJ, Westaway SK, Levinson B, et al (2003) Genetic, clinical, and radiographic delineation of Hallervorden–Spatz syndrome. N Engl J Med 348: 33–40.
Hofferberth B (1989) The effect of Ginkgo biloba extract on neurophysiological and psychometric measurement results in patients with psychotic organic brain syndrome. A double-blind study against placebo. Arzneimittelforschung 39: 918–922.
Hortnagel K, Prokisch H, Meitinger T (2003) An isoform of hPANK2, deficient in pantothenate kinase-associated neurodegeneration, localizes to mitochondria. Hum Mol Genet 12: 321–327.
Houlden H, Lincoln S, Farrer M, Cleland PG, Hardy J, Orrell RW (2003) Compound heterozygous PANK2 mutations confirm HARP and Hallervorden–Spatz syndromes are allelic. Neurology 61: 1423–1426.
Johnson MA, Kuo YM, Westaway SK, et al (2004) Mitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. Ann NY Acad Sci 1012: 282–298.
Kotzbauer PT, Truax AC, Trojanowski JQ, Lee VM (2005) Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. J Neurosci 25: 689–698.
Kuo YM, Duncan JL, Westaway SK, et al (2005) Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. Hum Mol Genet 14: 49–57.
Min KT, Benzer S (1999) Preventing neurodegeneration in the Drosophila mutant bubblegum. Science 284: 1985–1988.
Polich J, Gloria R (2001) Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory. Hum Psychopharmacol 16: 409–416.
Quaranta L, Bettelli S, Uva MG, Semeraro F, Turano R, Gandolfo E (2003) Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology 110: 359–362.
Tarnopolsky MA, Beal MF (2001) Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 49: 561–574.
Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ (2001) A novel pantothenate kinase gene (PANK2) is defective in Hallervorden–Spatz syndrome. Nature Genetice 28: 345–349.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, Y., Wu, Z., Kuo, Y.M. et al. Dietary rescue of fumble—a Drosophila model for pantothenate-kinase-associated neurodegeneration. J Inherit Metab Dis 28, 1055–1064 (2005). https://doi.org/10.1007/s10545-005-0200-0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10545-005-0200-0