scholarly journals Impact of Intravenous Trehalose Administration in Patients with Niemann–Pick Disease Types A and B

2022 ◽  
Vol 11 (1) ◽  
pp. 247
Author(s):  
Moein Mobini ◽  
Shabnam Radbakhsh ◽  
Francyne Kubaski ◽  
Peyman Eshraghi ◽  
Saba Vakili ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Symptoms ◽  
Serum Biomarkers ◽  
Acid Sphingomyelinase ◽  
Open Label ◽  
Niemann Pick Disease ◽  
Number Of Patients ◽  
Niemann Pick ◽  
Pick Disease

Background and Aims: Niemann–Pick disease (NPD) types A (NPA) and B (NPB) are caused by deficiency of the acid sphingomyelinase enzyme, which is encoded by the SMPD1 gene, resulting in progressive pathogenic accumulation of lipids in tissues. Trehalose has been suggested as an autophagy inducer with therapeutic neuroprotective effects. We performed a single-arm, open-label pilot study to assess the potential efficacy of trehalose treatment in patients with NPA and NPB patients. Methods: Five patients with NPD type A and B were enrolled in an open-label, single-arm clinical trial. Trehalose was administrated intravenously (IV) (15 g/week) for three months. The efficacy of trehalose in the management of clinical symptoms was evaluated in patients by assessing the quality of life, serum biomarkers, and high-resolution computed tomography (HRCT) of the lungs at the baseline and end of the interventional trial (day 0 and week 12). Results: The mean of TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients after intervention at W12 compared to the baseline W0, although the difference was not statistically significant. The serum levels of lyso-SM-509 and lyso-SM were decreased in three and four patients out of five, respectively, compared with baseline. Elevated ALT and AST levels were decreased in all patients after 12 weeks of treatment; however, changes were not statistically significant. Pro-oxidant antioxidant balance (PAB) was also decreased and glutathione peroxidase (GPX) activity was increased in serum of patients at the end of the study. Imaging studies of spleen and lung HRCT showed improvement of symptoms in two patients. Conclusions: Positive trends in health-related quality of life (HRQoL), serum biomarkers, and organomegaly were observed after 3 months of treatment with trehalose in patients with NPA and NPB. Although not statistically significant, due to the small number of patients enrolled, these results are encouraging and should be further explored.

scholarly journals Efficacy and safety of N-acetyl-l-leucine in Niemann–Pick disease type C

2021 ◽  
Author(s):  
Tatiana Bremova-Ertl ◽  
Jens Claassen ◽  
Tomas Foltan ◽  
Jordi Gascon-Bayarri ◽  
Paul Gissen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Washout Period ◽  
Rating Scales ◽  
Disease Type ◽  
Clinical Impression ◽  
Niemann Pick Disease ◽  
Type C ◽  
Niemann Pick ◽  
Pick Disease

Abstract Objective To investigate the safety and efficacy of N-acetyl-l-leucine (NALL) on symptoms, functioning, and quality of life in pediatric (≥ 6 years) and adult Niemann–Pick disease type C (NPC) patients. Methods In this multi-national, open-label, rater-blinded Phase II study, patients were assessed during a baseline period, a 6-week treatment period (orally administered NALL 4 g/day in patients ≥ 13 years, weight-tiered doses for patients 6–12 years), and a 6-week post-treatment washout period. The primary Clinical Impression of Change in Severity (CI-CS) endpoint (based on a 7-point Likert scale) was assessed by blinded, centralized raters who compared randomized video pairs of each patient performing a pre-defined primary anchor test (8-Meter Walk Test or 9-Hole Peg Test) during each study periods. Secondary outcomes included cerebellar functional rating scales, clinical global impression, and quality of life assessments. Results 33 subjects aged 7–64 years with a confirmed diagnosis of NPC were enrolled. 32 patients were included in the primary modified intention-to-treat analysis. NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029), as well as secondary endpoints. No treatment-related serious adverse events occurred. Conclusions NALL demonstrated a statistically significant and clinical meaningfully improvement in symptoms, functioning, and quality of life in 6 weeks, the clinical effect of which was lost after the 6-week washout period. NALL was safe and well-tolerated, informing a favorable benefit-risk profile for the treatment of NPC. Clinicaltrials.gov identifier NCT03759639.

scholarly journals Comparative Effects of Recombinant Acid Sphingomyelinase Administration by Different Routes in Niemann-Pick Disease Mice

2004 ◽  
Vol 53 (5) ◽  
pp. 417-421 ◽  
Author(s):  
Jae-Sung BAE ◽  
Kwang-Ho JANG ◽  
Edward H. SCHUCHMAN ◽  
Hee Kyung JIN
Keyword(s):  
Acid Sphingomyelinase ◽  
Niemann Pick Disease ◽  
Niemann Pick ◽  
Pick Disease

Acid sphingomyelinase deficiency: Prevalence and characterization of an intermediate phenotype of Niemann-Pick disease

2006 ◽  
Vol 149 (4) ◽  
pp. 554-559 ◽  
Author(s):  
Melissa P. Wasserstein ◽  
Alan Aron ◽  
Scott E. Brodie ◽  
Calogera Simonaro ◽  
Robert J. Desnick ◽  
...  
Keyword(s):  
Acid Sphingomyelinase ◽  
Intermediate Phenotype ◽  
Sphingomyelinase Deficiency ◽  
Niemann Pick Disease ◽  
Niemann Pick ◽  
Pick Disease

scholarly journals Infusion of recombinant human acid sphingomyelinase into Niemann‐Pick disease mice leads to visceral, but not neurological, correction of the pathophysiology

2000 ◽  
Vol 14 (13) ◽  
pp. 1988-1995 ◽  
Author(s):  
Silvia R. P. Miranda ◽  
Xingxuan He ◽  
Calogera M. Simonaro ◽  
Shimon Gatt ◽  
Arie Dagan ◽  
...  
Keyword(s):  
Acid Sphingomyelinase ◽  
Niemann Pick Disease ◽  
Human Acid ◽  
Niemann Pick ◽  
Pick Disease

Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann-Pick disease

2003 ◽  
Vol 284 (3) ◽  
pp. L518-L525 ◽  
Author(s):  
Machiko Ikegami ◽  
Rajwinder Dhami ◽  
Edward H. Schuchman
Keyword(s):  
Alveolar Macrophages ◽  
Pulmonary Inflammation ◽  
Acid Sphingomyelinase ◽  
Deficient Mouse ◽  
Niemann Pick Disease ◽  
Surfactant Inhibition ◽  
Niemann Pick ◽  
Surfactant Composition ◽  
Pick Disease

Types A and B Niemann-Pick disease (NPD) are lipid storage disorders caused by the deficient activity of acid sphingomyelinase (ASM). In humans, NPD is associated with the dysfunction of numerous organs including the lung. Gene targeting of the ASM gene in transgenic mice produced an animal model with features typical of NPD, including pulmonary inflammation. To assess mechanisms by which ASM perturbed lung function, we studied lung morphology, surfactant content, and metabolism in ASM-deficient mice in vivo. Pulmonary inflammation, with increased cellular infiltrates and the accumulation of alveolar material, was associated with alterations in surfactant content. Saturated phosphatidylcholine (SatPC) content was increased twofold, and sphingomyelin content was increased 5.5-fold in lungs of the ASM knockout (ASMKO) mice. Additional sphingomyelin enhanced the sensitivity of surfactant inhibition by plasma proteins. Clearance of SatPC from the lungs of ASMKO mice was decreased. Catabolism of SatPC by alveolar macrophages from the ASMKO mouse was significantly decreased, likely accounting for decreased pulmonary SatPC in vivo. In summary, ASM is required for normal surfactant catabolism by alveolar macrophages in vivo. Alterations in surfactant composition, including increased sphingomyelin content, contributed to the abnormal surfactant function observed in the ASM-deficient mouse.

scholarly journals Long-Term Neuropsychological Outcomes from an Open-Label Phase I/IIa Trial of 2-Hydroxypropyl-β-Cyclodextrins (VTS-270) in Niemann-Pick Disease, Type C1

CNS Drugs ◽  
2019 ◽  
Vol 33 (7) ◽  
pp. 677-683 ◽  
Author(s):  
Cristan A. Farmer ◽  
Audrey Thurm ◽  
Nicole Farhat ◽  
Simona Bianconi ◽  
Lee Ann Keener ◽  
...  
Keyword(s):  
Phase I ◽  
Disease Type ◽  
Open Label ◽  
Niemann Pick Disease ◽  
Open Label Phase ◽  
Neuropsychological Outcomes ◽  
Niemann Pick ◽  
Pick Disease

scholarly journals Cirrhosis and Liver Failure: Expanding Phenotype of Acid Sphingomyelinase-Deficient Niemann-Pick Disease in Adulthood

2014 ◽  
Author(s):  
Olivier Lidove ◽  
Frédéric Sedel ◽  
Frédéric Charlotte ◽  
Roseline Froissart ◽  
Marie T. Vanier
Keyword(s):  
Liver Failure ◽  
Acid Sphingomyelinase ◽  
Niemann Pick Disease ◽  
Niemann Pick ◽  
Pick Disease
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