Combined beta-glucosylceramide and ambroxol hydrochloride in patients with Gaucher related Parkinson disease: From clinical observations to drug development

Ishay, Yuval; Zimran, Ari; Szer, Jeffrey; Dinur, Tama; Ilan, Yaron; Arkadir, David

doi:10.1016/j.bcmd.2016.10.028

Cited by 16 publications

(6 citation statements)

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“…It has been shown to have an excellent side effect and safety profile both in vitro and in vivo, representing a particularly promising treatment strategy (Bendikov‐Bar et al, 2013). A recent review proposed that ambroxol hydrochloride combined with GlcCer could play a synergistic role in slowing down inflammation‐driven secondary neuronal death (Ishay et al, 2018). Recently, oral ambroxol (escalating dosage to 1.26 g/day) was shown to cross the blood–brain barrier, bind to GCase and decrease CSF α‐synuclein levels in an open‐label clinical trial in 17 patients with PD (Mullin et al, 2020).…”

Section: Sphingolipidsmentioning

confidence: 99%

Bioactive lipids and their metabolism: New therapeutic opportunities for Parkinson's disease

Shen

Jiang

Zhao

et al. 2022

Eur J of Neuroscience

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Parkinson's disease (PD) is a neurological disorder characterized by motor dysfunction, which can also be associated with non‐motor symptoms. Its pathogenesis is thought to stem from a loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of Lewy bodies containing aggregated α‐synuclein. Recent works suggested that lipids might play a pivotal role in the pathophysiology of PD. In particular, the so‐called ‘bioactive’ lipids whose changes in the concentration may lead to functional consequences and affect many pathophysiological processes, including neuroinflammation, are closely related to PD in terms of symptoms, disease progression and incidence. This study aimed to explore the molecular metabolism and physiological functions of bioactive lipids, such as fatty acids (mainly unsaturated fatty acids), eicosanoids, endocannabinoids, oxysterols, representative sphingolipids, diacylglycerols and lysophosphatidic acid, in the development of PD. The knowledge of bioactive lipids in PD gained through preclinical and clinical studies is expected to improve the understanding of disease pathogenesis and provide novel therapeutic avenues.

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Section: Sphingolipidsmentioning

confidence: 99%

Bioactive lipids and their metabolism: New therapeutic opportunities for Parkinson's disease

Shen

Jiang

Zhao

et al. 2022

Eur J of Neuroscience

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“…Finally, the increased risk of carriers may imply pre-test counselling for GD carrier screening (Mulhern, et al 2017). It is to be hoped that the results of the various clinical trials will ultimately lead to the prevention of PD in GBA carriers and patients with GD (Ishay, et al 2018).…”

Section: Author Manuscriptmentioning

confidence: 99%

How we manage Gaucher Disease in the era of choices

et al. 2018

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“…The laboratory AE of the reduction in the levels of uric acid detected in 8 out of all patients (20%), although asymptomatic, might be of some concern due to the fact that hypouricemia was reported in association with PD [ 23 ]. On the other hand, ABX may play a beneficial role in the management of GD-related PD and maybe even for the prevention of PD [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

High-Dose Ambroxol Therapy in Type 1 Gaucher Disease Focusing on Patients with Poor Response to Enzyme Replacement Therapy or Substrate Reduction Therapy

Istaiti

Frydman

Dinur

et al. 2023

IJMS

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Ambroxol hydrochloride (ABX), an oral mucolytic drug available over the counter for many years, acts as a pharmacological chaperone for mutant glucocerebrosidase, albeit at higher doses. Proof-of-concept reports have been published over the past decade on all three types of Gaucher disease (GD). Here, we assess the safety and efficacy of 12 months of 600 mg ambroxol per day in three groups of Type 1 GD patients with a suboptimal response to enzyme replacement therapy (ERT) or substrate reduction therapy (SRT), defined as platelet count < 100 × 103/L, lumbar spine bone density T-score < −2.0, and/or LysoGb1 > 200 ng/mL, and for a group of naïve patients who had abnormal values in two of these three parameters. We enrolled 40 patients: 28 ERT- or SRT-treated, and 12 naïve. There were no severe adverse effects (AEs). There were 24 dropouts, mostly due to AEs (n = 12), all transient, and COVID-19 (n = 7). Among the 16 completers, 5 (31.2%) had a >20% increase in platelet count, 6 (37.5%) had a >0.2 increase in T-score, and 3 (18.7%) had a >20% decrease in Lyso-Gb1. This study expands the number of patients exposed to high-dose ABX, showing good safety and satisfactory efficacy, and provides an additional rationale for adding off-label ABX to the arsenal of therapies that could be offered to patients with GD1 and a suboptimal response or those unable to receive ERT or SRT.

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Combined beta-glucosylceramide and ambroxol hydrochloride in patients with Gaucher related Parkinson disease: From clinical observations to drug development

Cited by 16 publications

References 50 publications

Bioactive lipids and their metabolism: New therapeutic opportunities for Parkinson's disease

Bioactive lipids and their metabolism: New therapeutic opportunities for Parkinson's disease

How we manage Gaucher Disease in the era of choices

High-Dose Ambroxol Therapy in Type 1 Gaucher Disease Focusing on Patients with Poor Response to Enzyme Replacement Therapy or Substrate Reduction Therapy

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