News Roundup: New and Noteworthy Information
Mutations of the KCNJ10 gene cause what investigators have called the EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy), according to a study in the May 7 New England Journal of Medicine. Investigators performed whole-genome linkage analysis in four children from one family. Heterologous expression system was used to evaluate newly identified mutations. The KCNJ10 gene encodes a potassium channel expressed in the brain, inner ear, and kidney. A single significant locus was found on chromosome 1q23.2 (logarithm of odds score, 4.98). Sequencing revealed homozygous missense mutations in affected persons from each family. “These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents,” the researchers stated. “Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.”
The FDA has announced that safety label changes are necessary for all botulinum toxin products, after reports emerged that the effects of the drug may spread to other areas of the body from the injection site. Changes include addition of a boxed warning and a Risk Evaluation and Mitigation Strategy (REMS). Symptoms including loss of strength, muscle weakness, hoarseness, loss of bladder control, breathing trouble, and vision problems have been mainly reported in children with cerebral palsy who were being treated for muscle spasticity, which is not an approved use of the products. Botulinum toxin type A, botulinum toxin type B, and abobotulinumtoxinA are required to add the new label. The REMS will include a medication guide and communication plan, which are given to patients when the medication is dispensed.
The FDA has required manufacturers of antiepileptic drugs (AEDs) or anticonvulsant drugs to update product labeling to include a warning about the increased risk of suicidal thoughts or actions, as well as develop a medication guide. The changes affect all approved AEDs except those that are indicated for short-term use only. All medication guides are expected to be available by the end of 2009. Patients currently taking or starting any AED should be monitored for behavioral changes.
Lower levels of 25-hydroxyvitamin D (25[OH]D) are associated with poorer cognitive function, according to a report in the May 21 online Journal of Neurology, Neurosurgery, and Psychiatry. A total of 3,369 men (ages 40 to 79) from eight centers in the European Male Ageing Study were assessed for cognitive function with use of three tests. Serum 25(OH)D levels were measured using radioimmunoassay, and associations were observed with locally weighted and linear regression models. “After adjusting for additional confounders, 25(OH)D levels were associated with the Digital Symbol Substitution Test only (beta per 10 nmol/L = 0.152),” investigators stated. “Locally weighted and spline regressions suggested the relationship between 25(OH)D and cognitive function was most pronounced at 25(OH)D concentrations below 35 nmol/L.”
Two years after beginning antidepressant therapy, patients have a higher risk of Parkinson’s disease, which suggests that depressive symptoms could be an early manifestation of the disease, according to a study in the June Journal of Neurology, Neurosurgery and Psychiatry. Cases of Parkinson’s disease (999) were selected from the General Practice Research Database cohort from 1995 to 2001 and matched with up to 10 controls (6,261) by age, sex, and practice. The rate ratio (RR) of Parkinson’s disease in initiators of antidepressant therapy compared with noninitiators was 1.85. “The association was stronger during the first two years after initiation of medication use (RR, 2.19) than later (RR, 1.23),” researchers stated. “Results were similar for selective serotonin reuptake inhibitors and tricyclic antidepressants separately.”
Vimpat (lacosamide), an antiepileptic drug (AED) approved by the FDA as add-on therapy in the treatment of partial-onset seizures in patients 17 and older, is now available in the United States. Vimpat is indicated for patients who have not yet achieved seizure control with their current therapy, as well as for those who have tried various other medications and are still having frequent seizures. No clinically significant pharmacokinetic drug interactions were observed with Vimpat when it was studied in combination with other AEDs. Vimpat is marketed by UCB.
Narcolepsy is associated with T-cell receptor alpha polymorphisms, according to a study in the May 3 online Nature Genetics. Following genome-wide association in Caucasians and replication in three other ethnic groups (1,830 cases, 2,164 controls), the highest significance was observed at rs1154155 (average allelic odds ratio [OR], 1.69; genotypic ORs, 1.94 and 2.55). “This is the first documented genetic involvement of the TRAα locus, encoding the major receptor for HLA-peptide presentation, in any disease,” researchers commented. How specific HLA alleles confer susceptibility to more than 100 HLA-associated disorders is still unclear. The investigators believe that narcolepsy might serve as a model for other HLA-associated disorders and provide new insight on how HLA-TCR interactions contribute to organ-specific autoimmune targeting.”
