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Open AccessArticle

Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease

1
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
2
Department of Pharmacology and Therapeutics, Western Gateway Building, College of Medicine and Health, University College Cork, T12XF62 Cork, Ireland
3
Department of Neurology and German Center for Vertigo and Balance Disorders, Ludwig Maximilians University of Munich, D-81377 Munich, Germany
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(4), 1050; https://doi.org/10.3390/jcm9041050
Received: 18 February 2020 / Revised: 23 March 2020 / Accepted: 2 April 2020 / Published: 8 April 2020
Sandhoff disease is a rare neurodegenerative lysosomal storage disease associated with the storage of GM2 ganglioside in late endosomes/lysosomes. Here, we explored the efficacy of acetyl-DL-leucine (ADLL), which has been shown to improve ataxia in observational studies in patients with Niemann–Pick Type C1 and other cerebellar ataxias. We treated a mouse model of Sandhoff disease (Hexb-/-) (0.1 g/kg/day) from 3 weeks of age with this orally available drug. ADLL produced a modest but significant increase in life span, accompanied by improved motor function and reduced glycosphingolipid (GSL) storage in the forebrain and cerebellum, in particular GA2. ADLL was also found to normalize altered glucose and glutamate metabolism, as well as increasing autophagy and the reactive oxygen species (ROS) scavenger, superoxide dismutase (SOD1). Our findings provide new insights into metabolic abnormalities in Sandhoff disease, which could be targeted with new therapeutic approaches, including ADLL. View Full-Text
Keywords: Sandhoff disease; acetyl-DL-Leucine; Tanganil; substrate reduction therapy; metabolism Sandhoff disease; acetyl-DL-Leucine; Tanganil; substrate reduction therapy; metabolism
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MDPI and ACS Style

Kaya, E.; Smith, D.A.; Smith, C.; Boland, B.; Strupp, M.; Platt, F.M. Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease. J. Clin. Med. 2020, 9, 1050. https://doi.org/10.3390/jcm9041050

AMA Style

Kaya E, Smith DA, Smith C, Boland B, Strupp M, Platt FM. Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease. Journal of Clinical Medicine. 2020; 9(4):1050. https://doi.org/10.3390/jcm9041050

Chicago/Turabian Style

Kaya, Ecem; Smith, David A.; Smith, Claire; Boland, Barry; Strupp, Michael; Platt, Frances M. 2020. "Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease" J. Clin. Med. 9, no. 4: 1050. https://doi.org/10.3390/jcm9041050

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