Trehalose in Machado-Joseph Disease: Safety, Tolerability, and Efficacy
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ORIGINAL ARTICLE
Trehalose in Machado-Joseph Disease: Safety, Tolerability, and Efficacy Roy Zaltzman 1,2 & Zohar Elyoseph 3 & Nirit Lev 1,2 & Carlos R. Gordon 1,2,4
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Machado-Joseph disease (MJD) is relatively prevalent among the Yemenite Jewish subpopulation living in Israel. Currently, there is no treatment able to modify the disease progression. Trehalose is a disaccharide with protein-stabilizing and autophagyenhancing properties. In animal models of MJD, trehalose showed reduction of cerebellar lesion size and improved motor function. This study was designed to be a proof-of-concept, phase 2 study lasting 6 to 12 months, to determine the safety, tolerability, and efficacy of weekly IV administration of 15 g or 30 g 10% trehalose solution in 14 MJD patients. Primary endpoints were safety and tolerability, which were assessed by various clinical and laboratory tests. Secondary endpoints were changes in the Scale for Assessment and Rating of Ataxia (SARA) score, Neurological Examination Score for Spinocerebellar Ataxia (NESSCA), time to do 9-hole peg test (9HPT), time to do 8-meter walk (8MW), and quality of life assessed by the World Health Organization Quality-of-Life Questionnaire-BREF (WHOQoL-BREF). Trehalose was well tolerated, and no serious drug-related adverse events were noted. The average SARA score, NESSCA, and time to do 9HPT and 8MW and the WHOQoL-BREF for all patients remained stable at 6 months. Six patients received treatment for as long as 12 months and continued to remain stable on all the above tests. IV trehalose seems to be safe in humans and probably effective to stabilize neurological impairment in MJD. Keywords Spinocerebellar ataxia . Machado-Joseph disease . Trehalose . Neurodegeneration
Introduction Machado-Joseph disease (MJD), also known as spinocerebellar ataxia (SCA) type 3, is an autosomal dominant (CAG repeat related) ataxia, first described in families of Portuguese-Azorean extraction in the USA [1–3]. Since then, MJD has been reported in many ethnic backgrounds, and is known to be the most common SCA worldwide [3]. In spite of Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12311-020-01150-6) contains supplementary material, which is available to authorized users. * Carlos R. Gordon [email protected] 1
Department of Neurology, Meir Medical Center, Kfar Saba, Israel
2
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
3
School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel
4
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
the fact that Israel has a population of very diverse origins, from all continents, the only patients with MJD in Israel are of Yemenite origin, among which it is relatively prevalent [4]. MJD is a neurodegenerative disorder involving predominantly the cerebellar system. The clinical picture becomes complex, when other parts of the nervous systems are involved, such as
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