Markers of cognitive function in individuals with metabolic disease: Morquio Syndrome and Tyrosinemia Type III

We characterized cognitive function in two metabolic diseases. MPS–IVa (mucopolysaccharidosis IVa, Morquio) and tyrosinemia type III individuals were assessed using tasks of attention, language and oculomotor function. MPS–IVa individuals were slower in visual search, but the display size effects were normal, and slowing was not due to long reaction times (ruling out slow item processing or distraction). Maintaining gaze in an oculomotor task was difficult. Results implicated sustained attention and task initiation or response processing. Shifting attention, accumulating evidence and selecting targets were unaffected. Visual search was also slowed in tyrosinemia type III, and patterns in visual search and fixation tasks pointed to sustained attention impairments, although there were differences from MPS–IVa. Language was impaired in tyrosinemia type III but not MPS–IVa. Metabolic diseases produced selective cognitive effects. Our results, incorporating new methods for developmental data and model selection, illustrate how cognitive data can contribute to understanding function in biochemical brain systems

Elosulfase alfa (BMN 110) for the treatment of Mucopolysaccharidosis IVA (Morquio A syndrome)

INTRODUCTION : Morquio A syndrome is a rare, autosomal recessive, lysosomal storage disorder caused bya deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (GALNS). In 2014, the use of recombinant human GALNS, elosulfase alfa, was approved in Europe, Canada, the United States, Australia, and Brazil for the treatment of Morquio A syndrome. Elosulfase alfa is administered intravenously once-weekly at a dose of 2.0 mg/kg. AREAS COVERED : This is a review of the efficacy, safety and tolerability, pharmacokinetics and pharmacodynamics, and other outcomes of elosulfase alfa treatment of patients with Morquio A. A discussion of other treatment considerations, limitations, and future directions in the use of elosulfase alfa is provided. EXPERT COMMENTARY : Pharmacokinetic studies outside of clinical trials and in “real-world” clinical settings need to be performed. We cannot currently predict which patient is going to respond well to enzyme replacement therapy; thus, all patients should be given the option to receive treatment for at least 12 months. Additionally, accurate biomarkers for evaluating disease state and drug responsiveness would greatly aid in the treatment of patients with Morquio A. In addition, improved and innovative daily lifestyle measures are greatly needed to adequately measure clinical response and true impact on quality of life.Medical writing and editorial support was provided by PharmaWrite, LLC, and funded by BioMarin Pharmaceutical Inc.http://tandfonline.com/toc/ierj202017-11-23hb2016Immunolog

International guidelines for the management and treatment of Morquio A syndrome.

Morquio A syndrome (mucopolysaccharidosis IVA) is a lysosomal storage disorder associated with skeletal and joint abnormalities and significant non-skeletal manifestations including respiratory disease, spinal cord compression, cardiac disease, impaired vision, hearing loss, and dental problems. The clinical presentation, onset, severity and progression rate of clinical manifestations of Morquio A syndrome vary widely between patients. Because of the heterogeneous and progressive nature of the disease, the management of patients with Morquio A syndrome is challenging and requires a multidisciplinary approach, involving an array of specialists. The current paper presents international guidelines for the evaluation, treatment and symptom-based management of Morquio A syndrome. These guidelines were developed during two expert meetings by an international panel of specialists in pediatrics, genetics, orthopedics, pulmonology, cardiology, and anesthesia with extensive experience in managing Morquio A syndrome

Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc