Posts tagged drug

July 18, 2012

A new guideline released by the American Academy of Neurology recommends several treatments for people with Huntington’s disease who experience chorea—jerky, random, uncontrollable movements that can make everyday activities challenging. The guideline is published in the July 18, 2012, online issue of Neurology.

"Chorea can be disabling, worsen weight loss and increase the risk of falling," said guideline lead author Melissa Armstrong, MD, MSc, with the University of Maryland Department of Neurology and a member of the American Academy of Neurology.

Huntington’s disease is a complex disease with physical, cognitive and behavioral symptoms. The new guideline addresses only one aspect of the disease that may require treatment.

The guideline found that the drugs tetrabenazine (TBZ), riluzole and amantadine can be helpful and the drug nabilone may also be considered to treat chorea. The medications riluzole, amantadine and nabilone are not often prescribed for Huntington’s disease.

"People with Huntington’s disease who have chorea should discuss with their doctors whether treating chorea is a priority. Huntington’s disease is complex with a wide range of sometimes severe symptoms and treating other symptoms may be a higher priority than treating chorea," said Armstrong.

Armstrong adds that it is important for patients to understand that their doctors may try drugs not recommended in this guideline to treat chorea. More research is needed to know if drugs such as those used for psychosis are effective; however, doctors may prescribe them on the basis of past clinical experience.

Provided by American Academy of Neurology

Source: medicalxpress.com

ScienceDaily (July 17, 2012) — Scientists have discovered two genetic variants associated with the substantial, rapid weight gain occurring in nearly half the patients treated with antipsychotic medications, according to two studies involving the Centre for Addiction and Mental Health (CAMH).

These results could eventually be used to identify which patients have the variations, enabling clinicians to choose strategies to prevent this serious side-effect and offer more personalized treatment.

"Weight gain occurs in up to 40 per cent of patients taking medications called second-generation or atypical antipsychotics, which are used because they’re effective in controlling the major symptoms of schizophrenia," says CAMH Scientist Dr. James Kennedy, senior author on the most recent study published online in the Archives of General Psychiatry.

This weight gain can lead to obesity, type 2 diabetes, heart problems and a shortened life span. “Identifying genetic risks leading to these side-effects will help us prescribe more effectively,” says Dr. Kennedy, head of the new Tanenbaum Centre for Pharmacogenetics, which is part of CAMH’s Campbell Family Mental Health Research Institute. Currently, CAMH screens for two other genetic variations that affect patients’ responses to psychiatric medications.

Each study identified a different variation near the melanocortin-4 receptor (MC4R) gene, which is known to be linked to obesity.

In the Archives of General Psychiatry study, people carrying two copies of a variant gained about three times as much weight as those with one or no copies, after six to 12 weeks of treatment with atypical antipsychotics. (The difference was approximately 6 kg versus 2 kg.) The study had four patient groups: two from the U.S., one in Germany and one from a larger European study.

"The weight gain was associated with this genetic variation in all these groups, which included pediatric patients with severe behaviour or mood problems, and patients with schizophrenia experiencing a first episode or who did not respond to other antipsychotic treatments," says CAMH Scientist Dr. Daniel Müller. "The results from our genetic analysis combined with this diverse set of patients provide compelling evidence for the role of this MC4R variant. Our research group has discovered other gene variants associated with antipsychotic-induced weight gain in the past, but this one appears to be the most compelling finding thus far."

Three of the four groups had never previously taken atypical antipsychotics. Different groups were treated with drugs such as olanzapine, risperidone, aripiprazole or quetiapine, and compliance was monitored to ensure the treatment regime was followed. Weight and other metabolic-related measures were taken at the start and during treatment.

A genome-wide association study was conducted on pediatric patients by the study’s lead researcher, Dr. Anil Malhotra, at the Zucker Hillside Hospital in Glen Oaks, NY. In this type of study, variations are sought across a person’s entire set of genes to identify those associated with a particular trait. The result pointed to the MC4R gene.

This gene’s role in antipsychotic-induced weight gain had been identified in a CAMH study published earlier this year in The Pharmacogenomics Journal, involving Drs. Müller and Kennedy, and conducted by PhD student Nabilah Chowdhury. They found a different variation on MC4R that was linked to the side-effect.

For both studies, CAMH researchers did genotyping experiments to identify the single changes to the sequence of the MC4R gene — known as single nucleotide polymorphisms (SNPs) — related to the drug-induced weight gain side-effect.

The MC4R gene encodes a receptor involved in the brain pathways regulating weight, appetite and satiety. “We don’t know exactly how the atypical antipsychotics disrupt this pathway, or how this variation affects the receptor,” says Dr. Müller. “We need further studies to validate this result and eventually turn this into a clinical application.”

Source: Science Daily

ScienceDaily (July 17, 2012) — Researchers at the University of Colorado School of Medicine have found a drug that boosts memory function in those with Down syndrome, a major milestone in the treatment of this genetic disorder that could significantly improve quality of life.

"Before now there had never been any positive results in attempts to improve cognitive abilities in persons with Down syndrome through medication," said Alberto Costa, MD, Ph.D., who led the four- year study at the CU School of Medicine. "This is the first time we have been able to move the needle at all and that means improvement is possible."

The study was published July 17 in the journal Translational Psychiatry.

Costa, an associate professor of medicine, and his colleagues studied 38 adolescents and young adults with Down syndrome. Half took the drug memantine, used to treat Alzheimer’s disease, and the others took a placebo.

Costa’s research team hypothesized that memantine, which improved memory in mice with Down syndrome, could increase test scores of young adults with the disorder in the area of spatial and episodic memory, functions associated with the hippocampus region of the brain.

Participants underwent a 16-week course of either memantine or a placebo while scientists compared the adaptive and cognitive function of the two groups.

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Article Date: 16 Feb 2012 - 1:00 PST

Scientists at Emory University School of Medicine have identified a new group of compounds that may protect brain cells from inflammation linked to seizures and neurodegenerative diseases.

The compounds block signals from EP2, one of the four receptors for prostaglandin E2, which is a hormone involved in processes such as fever, childbirth, digestion and blood pressure regulation. Chemicals that could selectively block EP2 were not previously available. In animals, the EP2 blockers could markedly reduce the injury to the brain induced after a prolonged seizure, the researchers showed.

The results were published online this week in the Proceedings of the National Academy of Sciences Early Edition.

“EP2 is involved in many disease processes where inflammation is showing up in the nervous system, such as epilepsy, stroke and neurodegenerative diseases,” says senior author Ray Dingledine, PhD, chairman of Emory’s Department of Pharmacology. “Anywhere that inflammation is playing a role via EP2, this class of compounds could be useful. Outside the brain, EP2 blockers could find uses in other diseases with a prominent inflammatory component such as cancer and inflammatory bowel disease.”

Prostaglandins are the targets for non-steroid anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen. NSAIDSs inhibit enzymes known as cyclooxygenases, the starting point for generating prostaglandins in the body. Previous research indicates that drugs that inhibit cyclooxygenases can have harmful side effects. For example, sustained use of aspirin can weaken the stomach lining, coming from prostaglandins’ role in the stomach. Even drugs designed to inhibit only cyclooxygenases involved in pain and inflammation, such as Vioxx, have displayed cardiovascular side effects.

Dingledine’s team’s strategy was to bypass cyclooxygenase enzymes and go downstream, focusing on one set of molecules that relay signals from prostaglandins. Working with Yuhong Du in the Emory Chemical Biology Discovery Center, postdoctoral fellows Jianxiong Jiang, Thota Ganesh and colleagues sorted through a library of 262,000 compounds to find those that could block signals from the EP2 prostaglandin receptor but not related receptors. One of the compounds could prevent damage to neurons in mice after “status epilepticus,” a prolonged drug-induced seizure used to model the neurodegeneration linked to epilepsy. The team found that a family of related compounds had similar protective effects.

Dingledine says that the compounds could become valuable tools for exploring new ways to treat neurological diseases. However, given the many physiological processes prostaglandins regulate, more tests are needed, he says. Prostaglandin E2 is itself a drug used to induce labor in pregnant women, and female mice engineered to lack the EP2 receptor are infertile, so the compounds would need to be tested for effects on reproductive organs, for example.

View drug information on Vioxx.

Source: Medical News Today