Posts By: Yannis Trakadis

Intranasal ERT in LSDs may bypass BBB


According to the study by Wolf et al. intranasal administration of α-l-iduronidase (IDUA) enzyme may be able to bypass the blood-brain barrier. This appears to be the case in IDUA-deficient mice after a single intranasal treatment with concentrated Aldurazyme®. Promising results in mice were also noted after intranasal treatment with an adeno-associated virus (AAV) vector expressing […]

siRNA based drugs & vaccines?

Posted by & filed under In the news.

Short interfering RNAs (siRNAs) are RNA strands designed to bind to target strands of mRNA and knock down the expression of targeted genes, thus preventing the synthesis of the respective proteins. Special interest in recent years about using siRNAs to target key disease proteins has been suppressed due to the difficulty of having the siRNAs […]

de novo mutations and autism

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Sanders et al. completed whole-exome sequencing in 238 families from the Simons Simplex Collection (SSC). SSC is a comprehensively phenotyped autism spectrum disorders cohort consisting of pedigrees with two unaffected parents, an affected proband, and, in 200 families, an unaffected sibling. Based on the results of whole-exome sequencing of a total of 928 individuals Sanders […]

Extrachromosomal circular DNA: microDNA

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Shibata et al. identified a new form of Extrachromosomal circular DNA (microDNA) in mouse tissues as well as human cell lines. These microDNAs are 200 to 400 bp long. Unlike formerly described Extrachromosomal circular DNA, they are not derived from repetitive sequences, transposable elements, or viral genomes. They are derived from unique nonrepetitive genomic sequences […]

Liver-targeted gene therapy in PKU mice: neurogenic amines & neuropsych function

Posted by & filed under Part 08: AMINO ACIDS, Treatment.

Aminergic deficit is one of the abnormalities found in the brain of hyperphenylalaninemic patients and a mouse model of PKU. Liver-targeted gene therapy has been previously reported to correct hyperphenylalaninemia and concomitant behavioral recovery in PKU mice. In this study Yagi et al. provide evidence that the functional recovery is mediated by reversal of the […]

Intellectual impairment after long-term NTBC treatment?

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Treatment of hypertyrosinemia (HT) type I with NTBC can prevent acute liver failure and hepatocellular carcinoma thus improving survival of patients. However, there is some evidence of cognitive impairment in patients with secondary elevated plasma tyrosine levels. Thimm et al. used standardized psychometric test batteries to evaluate the neurocognitive development (cognition, motor abilities and speech) […]

ERT and adult Pompe disease outcome

Posted by & filed under Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT, Treatment.

Regnery et al (2012) performed an open-label observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 38 adult patients with GSD2. The patients first presented with the disease at a mean age of 36.2 ± 10.5 years but ERT treatment was only started after  14.5 ± 7.2 years (mean delay). This study demonstrates a variable course of neuromuscular deficits during […]

Treatable IEM causing intellectual disability

Posted by & filed under Part 06: DIAGNOSTIC APPROACHES, Treatment, Websites.

Dr. van Karnebeek and Dr. Stockler performed a systematic literature review for treatable inborn errors of metabolism causing intellectual disability. Recommendations for investigation of genetic causes of intellectual disability are usually based on the frequencies of single conditions and the yield of diagnostic methods. The objective of this manuscript was to identify all currently treatable […]

New treatments for Angelman syndrome?

Posted by & filed under Part 28: NEUROGENETICS, _.

Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Huang HS et al. Nature. 2011 Dec 21. Angelman syndrome is a genetic disorder characterized by severe developmental delay, severe speech impairment, gait ataxia and/or tremulousness of the limbs, as well as typical behaviour. It is an imprinting disorder caused by changes in the maternal […]

Kufs disease, adult NCL, gene

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The Neuronal Ceroid Lipofuscinoses (NCLs) are characterized by neuronal degeneration and the intracellular accumulation of autofluorescent ceroid lipopigments. Cases are clinically categorized by age of onset into infantile, late-infantile, juvenile, and adult NCL. The majority of NCLs present in infants and children and the genes accounting for most of the childhood-onset NCL have been identified. […]