Posts Categorized: Treatment

MTTP allele as a risk factor for metabolic syndrome with atypical antipsychotics

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

Liou et al. recently published a study illustrating that promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) are associated with metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. 456 hospitalized patients with schizophrenia, who had been treated with clozapine (n = 171), olanzapine (n = 91), or risperidone (n = 194) for at least […]

Long-term BH4 responsive PKU patients

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

There are no established criteria for the identification of patients with phenylketonuria who are long-term BH4 responsive. Hennermann et al. reported that, based on their cohort of patients, long-term BH4 responsiveness may be predicted already during neonatal period by determining maximum pretreatment phenylalanine and phenylalanine/tyrosine concentrations, neonatal BH4 loading and PAH genotype. The most predictive […]

Genetic engineering treatment with zinc-finger nucleases

Posted by & filed under Treatment.

The most lethal etiologic agent of malaria is the Plasmodium falciparum parasite. Straimer et al. (2012) report on the successful genetic engineering of Plasmodium falciparum using zinc-finger nucleases (ZFNs), as a potential treatment for malaria refractory to existing medication. ZFNs produce a double-strand break in a user-defined locus and trigger homology-directed repair. To realize the […]

Nitisinone (NTBC) in Hepatorenal tyrosinemia

Posted by & filed under Newborn screening, Treatment.

Hepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency), can cause severe hepatic, renal and peripheral nerve damage. The clinical course of 78 patients was studied in Quebec. Of note, in Quebec HT1 is more frequent and is part of the neonatal screening program. Nitisinone (NTBC) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone […]

Cyclocreatine for therapy of creatine transporter deficiency

Posted by & filed under Part 21: MEMBRANE TRANSPORT DISORDERS, Treatment.

The second most common cause of X-linked mental retardation is the deficiency of creatine transporter (encoded by SLC6A8), which leads to speech and language disorders with severe cognitive impairment. This syndrome is caused by cerebral creatine deficiency. Kurosawa et al. have treated the Slc6a8–/y mice with cyclocreatine, a creatine analog which is more susceptible to […]

Targeting nuclear RNA for in vivo correction of myotonic dystrophy.

Posted by & filed under Part 25: MUSCLE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT, Treatment.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder characterized by myotonia, weakness, cardiac arrhythmias, diabetes and cognitive deficits. Patients carry an expansion of the CTG DNA repeat sequence in the DMPK gene. As a result, when the mutant gene is expressed, it yields a toxic messenger RNA molecule (a gain-of-function effect). In addition […]

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 […]

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?

Posted by & filed under Treatment.

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 […]