Click Chemistry Enables [Zr]Zr-DOTA Radioimmunoconjugation for Theranostic Zr-immunoPET.

There have been predictions that the use of the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in zirconium-89 (Zr) immuno-positron emission tomography (Zr-immunoPET) could enhance the in vivo stability of Zr radioimmunoconjugates. However, conjugating [Zr]Zr-DOTA to a monoclonal antibody (mAb) remains a challenge as the heat treatment required for [Zr]Zr-DOTA chelation can lead to thermal denaturation of the mAb moieties. We developed a method for synthesizing [Zr]Zr-DOTA-mAb based on a tetrazine (Tz)-conjugated bifunctional DOTA derivative 2,2',2″-(10-(1-(4-(1,2,4,5-tetrazin-3-yl)phenyl)-3,21,26-trioxo-6,9,12,15,18-pentaoxa-29-carboxy-2,22,25-triazanonacosane-29-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-Tz) and the inverse electron-demand Diels-Alder (IEDDA) click chemistry reaction where -cyclooctene-modified mAbs are conjugated to [Zr]Zr-DOTAGA without being exposed to heat.

Allele frequency of pathogenic variants causing acid sphingomyelinase deficiency and Gaucher disease in the general Japanese population.

Acid sphingomyelinase deficiency (ASMD) and Gaucher disease (GD) are lysosomal storage disorders associated with hepatosplenomegaly and thrombocytopenia. The incidences of ASMD and GD are known to be particularly high in the Ashkenazi Jewish population. Conversely, the number of reported patients with these diseases has been limited in Asian countries, including Japan.

Adverse Events in Pediatric Inpatients: The Japan Adverse Event Study.

Objectives: Adverse events (AEs) represent an important cause of morbidity and mortality for pediatric inpatients; however, reports on their epidemiology in pediatrics, especially outside Western countries, are scarce. We investigated the incidence and nature of AEs in pediatric inpatients in Japan.

Methods: Trained pediatrician and pediatric nurses reviewed all medical documents of 1126 pediatric inpatients in 2 tertiary care teaching hospitals in Japan, and potential incidents were collected with patients' characteristics.

An observational study to investigate the relationship between plasma glucosylsphingosine (lyso-Gb1) concentration and treatment outcomes of patients with Gaucher disease in Japan.

Background: Gaucher disease (GD) is an autosomal recessive disease caused by GBA1 mutations resulting in glucosylceramide accumulation in macrophages. GD is characterized by hepatosplenomegaly, anemia, thrombocytopenia, bone complications, and neurological complications. Glucosylsphingosine (lyso-Gb1), a deacylated form of glucosylceramide, has been identified as a promising biomarker for the diagnosis and treatment response in GD.

Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: the LEAP trial.

Gaucher disease type 3 is a chronic neuronopathic disorder with wide-ranging effects, including hepatosplenomegaly, anaemia, thrombocytopenia, skeletal disease and diverse neurological manifestations. Biallelic mutations in GBA1 reduce lysosomal acid β-glucosidase activity, and its substrates, glucosylceramide and glucosylsphingosine, accumulate. Enzyme replacement therapy and substrate reduction therapy ameliorate systemic features of Gaucher disease, but no therapies are approved for neurological manifestations.

Erratum: Hematopoietic stem cell gene therapy ameliorates CNS involvement in murine model of GM1-gangliosidosis.

[This corrects the article DOI: 10.1016/j.omtm.

The role of native T1 values on the evaluation of cardiac manifestation in Japanese Fabry disease patients.

Aims: T1 mapping in cardiac magnetic resonance imaging enables us to distinguish various myocardial diseases showing left ventricular hypertrophy. Fabry disease is a lysosomal storage disorder causing the accumulation of glycosphingolipids into various organs, including the heart, which can be detected by native T1 values in T1 mapping. However, there is no report for the systematic evaluation of native T1 values in Fabry disease in Japan.

Hematopoietic stem cell gene therapy ameliorates CNS involvement in murine model of GM1-gangliosidosis.

GM1-gangliosidosis is a progressive neurodegenerative glycosphingolipidosis resulting from a gene mutation causing a deficiency of the lysosomal enzyme β-galactosidase, which leads to the abnormal accumulation of GM1 ganglioside in the central nervous system. In the most severe early infantile phenotype, excessive ganglioside accumulation results in a rapid decline in neurological and psychomotor functions, and death occurs within 2 years of age. Currently, there is no effective therapy for GM1-gangliosidosis.

Treatment Satisfaction and Its Influencing Factors in Parkinson's Disease: A Web-Based Survey of Patients and Physicians in Clinical Practice in Japan.

Objective: This study aimed to gain an understanding of patient and physician satisfaction with overall treatment and routine consultations for Parkinson's disease in clinical practice.

Methods: This observational, cross-sectional, web-based survey was conducted in Japan from February to March 2019. Eligible patients with Parkinson's disease ( = 186) and physicians who treat patients with Parkinson's disease ( = 331) were asked to evaluate their satisfaction with treatment, consultation, symptom control, and use of a symptom diary.

Radiolabeling of PSMA-617 with Zr: A novel use of DMSO to improve radiochemical yield and preliminary small-animal PET results.

Introduction: Novel diagnostic and therapeutic options are urgently needed for patients with metastatic castration-resistant prostate cancer (CRPC). PSMA-617 is one of the most promising ligands that bind to prostate specific membrane antigen (PSMA), the cell surface biomarker of CRPC. Of the radiolabeled PSMA ligands developed to date, [Ga]Ga-PSMA-617 is most commonly used for PSMA positron emission tomography (PET) prior to radioligand therapy (RLT) with [Lu]Lu-PSMA-617.

Long-term efficacy of low-dose perampanel for progressive myoclonus epilepsy in a patient with Gaucher disease type 3.

Purpose: We report the case of a patient with progressive myoclonus epilepsy due to Gaucher disease type 3 whose seizures and ability to perform activities of daily living were significantly improved after starting low-dose perampanel therapy.

Case: Our patient's generalized tonic-clonic seizures and myoclonus did not improve despite the administration of multiple antiseizure medications and enzyme replacement therapy. The myoclonus reduced following pharmacological chaperone therapy, but this effect was temporary, and the generalized tonic-clonic seizures continued to occur.

Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan.

Background: Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with type 1 GD, the least severe form of GD.

A Japanese Patient with Gaucher Disease Treated with the Oral Drug Eliglustat as Substrate Reducing Therapy.

Gaucher disease is a rare genetic disorder caused by the deficiency of acid β-glucosidase to effectively catalyze the degradation of glucosylceramide to glucose and ceramide. We report here the case of a 31-year-old male Japanese patient with Gaucher disease who switched from enzyme replacement therapy (ERT) to substrate reducing therapy (SRT). Liver dysfunction was identified at a routine medical checkup, and the patient was referred to our hospital with "idiopathic liver disease.

The function of Scox in glial cells is essential for locomotive ability in Drosophila.

Synthesis of cytochrome c oxidase (Scox) is a Drosophila homolog of human SCO2 encoding a metallochaperone that transports copper to cytochrome c, and is an essential protein for the assembly of cytochrome c oxidase in the mitochondrial respiratory chain complex. SCO2 is highly conserved in a wide variety of species across prokaryotes and eukaryotes, and mutations in SCO2 are known to cause mitochondrial diseases such as fatal infantile cardioencephalomyopathy, Leigh syndrome, and Charcot-Marie-Tooth disease, a neurodegenerative disorder. These diseases have a common symptom of locomotive dysfunction.

Re-Evaluations of Zr-DFO Complex Coordination Chemistry for the Estimation of Radiochemical Yields and Chelator-to-Antibody Ratios of Zr Immune-PET Tracers.

(1) Background: Deferoxamine B (DFO) is the most widely used chelator for labeling of zirconium-89 (Zr) to monoclonal antibody (mAb). Despite the remarkable developments of the clinical Zr-immuno-PET, chemical species and stability constants of the Zr-DFO complexes remain controversial. The aim of this study was to re-evaluate their stability constants by identifying species of Zr-DFO complexes and demonstrate that the stability constants can estimate radiochemical yield (RCY) and chelator-to-antibody ratio (CAR).

A 23-year follow-up report of juvenile-onset Sandhoff disease presenting with a motor neuron disease phenotype and a novel variant.

Background: The clinical severity of Sandhoff disease is known to vary widely. Furthermore, long-term follow-up report is very limited in the literature.

Case Presentation: We present a long-term follow-up report of a patient with juvenile-onset Sandhoff disease with a motor neuron disease phenotype.

Pectus carinatum as the key to early diagnosis of Morquio A syndrome: a case report.

Background: A 20-month-old Asian boy with normal growth presented with genu valgum, kyphosis, and pectus carinatum, with no neurological symptoms. No other symptoms suggestive of mucopolysaccharidoses, for example joint contracture and peculiar facies, were present.

Case Presentation: As part of our differential diagnosis we found elevated urine glycosaminoglycans, which triggered further investigation.

The Burden of Preventable Adverse Drug Events on Hospital Stay and Healthcare Costs in Japanese Pediatric Inpatients: The JADE Study.

Background: Adverse drug events (ADEs) are a burden to the healthcare system. Preventable ADEs, which was ADEs due to medication errors, could be reduced if medication errors can be prevent or ameliorate.

Objective: We investigated the burden of preventable ADEs on the length of hospital stay (LOS) and costs, and estimated the national burden of preventable ADEs in pediatric inpatients in Japan.

Familial juvenile hyperuricemia in early childhood in a boy with a novel gene mutation.

Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal dominant disease caused by mutations in the uromodulin (UMOD) gene. It is characterized by the development of gout, tubulointerstitial nephropathy, and end-stage renal disease. Here we report a case of FJHN that was diagnosed in early childhood in a boy with a novel gene mutation.

Successful treatment of Gaucher disease type 1 by enzyme replacement therapy over a 10-year duration in a Japanese pediatric patient: A case report.

The prevalence of Gaucher disease (GD) in Japan is much lower than that in Western countries; therefore, data on Japanese pediatric patients with GD type 1 are currently limited. The present study reports on the case of a Japanese pediatric patient with GD type 1 who was diagnosed when she presented with hepatosplenomegaly, thrombocytopenia and slight anemia at the age of 2 years. Serology tests revealed high levels of acid phosphatase (ACP) and angiotensin-converting enzyme (ACE).

Characteristics of the Electrocardiogram in Japanese Fabry Patients Under Long-Term Enzyme Replacement Therapy.

An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT). We analyzed the ECGs of 40 Fabry patients (male, = 17; female, = 23) before and after treatment with ERT.

Guide for diagnosis and treatment of hyperphenylalaninemia.

Importance: Sapropterin hydrochloride, a natural coenzyme (6R-tetrahydrobiopterin) of phenylalanine hydroxylase, was first approved as a treatment for tetrahydrobiopterin deficiency in 1992 in Japan, and was then approved as a treatment for a tetrahydrobiopterin-responsive hyperphenylalaninemia in 2007 and 2008, in the USA and Japan, respectively. Guidelines are required on the proper use of sapropterin hydrochloride for tetrahydrobiopterin-responsive hyperphenylalaninemia.

Observations: It is recommended that tetrahydrobiopterin-responsive hyperphenylalaninemia should be diagnosed in all cases of hyperphenylalaninemia, including phenylketonuria, by tetrahydrobiopterin administration tests rather than by phenotype or blood phenylalanine levels.

Sliding Aortoplasty for Severe Supravalvular Aortic Stenosis After the Lecompte Procedure.

This report describes the case of a 3-year-old boy with supravalvular aortic stenosis after an arterial switch operation in whom the stenosis was successfully repaired using an ascending sliding arch aortoplasty without using a patch. Because patches were avoided, growth of the surgical site is expected. Ascending sliding arch aortoplasty and longitudinal expansion of the pulmonary bifurcation are useful for relieving stenosis and preventing supravalvular aortic stenosis recurrence after an arterial switch operation.

Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation.

Mucopolysaccharidosis type II is a disease caused by organ accumulation of glycosaminoglycans due to iduronate 2-sulfatase deficiency. This study investigated the pathophysiology of the bone complications associated with mucopolysaccharidosis II and the effect of lentivirus-mediated gene therapy of hematopoietic stem cells on bone lesions of mucopolysaccharidosis type II mouse models in comparison with enzyme replacement therapy. Bone volume, density, strength, and trabecular number were significantly higher in the untreated mucopolysaccharidosis type II mice than in wild-type mice.