Researchers may have discovered how West Nile virus enters the brain, according to a study in the December Nature Medicine. They found that a protein known as Toll-like receptor 3 induces an inflammatory response in mice that results in increased permeability of the blood-brain barrier, enabling the virus to enter the central nervous system. Results of the study could lead to the development of treatments for West Nile virus and may help researchers to understand how other viruses that affect the nervous system, such as Herpes simplex virus, invade the brain.

Women who are overweight or obese throughout life are more likely to have brain atrophy, according to a report in the November 23 Neurology. Researchers evaluated a group of 290 women for a period of 24 years and found that a body mass index (BMI) of 25 or higher was linked to temporal atrophy in 50% of the women studied. The risk of atrophy increased 13% to 16% per 1.0 kg/m² increase in BMI. The researchers said their findings indicate “that a high BMI is a risk factor for dementia in women.” They recommended the use of interventions for obesity to prevent diseases of advanced aging.

Biogen Idec and Elan Corporation, plc, announced that the FDA has approved natalizumab for the treatment of relapsing multiple sclerosis. The accelerated approval of the treatment was based on two randomized, placebo-controlled, double blind trials. In the first trial, patients were randomized to either a fixed 300-mg intravenous infusion dose of natalizumab or placebo every four weeks. Natalizumab reduced the rate of relapse by 66%. In the second trial, patients treated with interferon beta-1a who continued to experience disease activity were randomized to add either natalizumab or placebo to their treatment regimen. The addition of natalizumab reduced the rate of relapse by 54%, compared with interferon beta-1a alone. Natalizumab is thought to work by inhibiting adhesion molecules on the surface of immune cells.

Neurologic complications were associated with influenza A infection in children during the 2003-2004 influenza season in Houston, according to an article in the November Pediatrics. Researchers reviewed the medical and laboratory records of eight children ages 5 months to 9 years who were hospitalized with neurologic symptoms and influenza virus infection during October and November 2003. The investigators found that four patients presented with seizures, three with mental status changes, and one had become mute. Three patients had brain-imaging abnormalities. The researchers said, “Influenza should be considered in the differential diagnosis in patients with seizures and mental status changes, especially if they present with respiratory symptoms or during an influenza outbreak.”

High levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with an increased risk of ischemic stroke, according to research presented at the American Heart Association’s Scientific Sessions 2004. Investigators found that patients with higher levels of Lp-PLA2 had double the risk of suffering an ischemic stroke over a period of six years. This remained true even after risk factors such as systolic blood pressure, smoking status, and diabetes were accounted for. Researchers also found that patients with high levels of both Lp-PLA2 and C-reactive protein (CRP) had more than an 11-fold increased risk of stroke, compared with patients with low levels of both Lp-PLA2 and CRP. The investigators noted that “ongoing research is evaluating whether Lp-PLA2 is an important therapeutic target to reduce stroke.”

Antipsychotic drugs can protect brain cells against the JC virus, which causes progressive multifocal leukoencephalopathy in immunocompromised patients, according to a study in the November 19 Science. After discovering that the JC virus binds to 5HT_2A receptors—which usually bind with serotonin, a compound responsible for depression and anxiety—researchers decided to examine the effectiveness of the antipsychotic chlorprozamine in preventing infection in glial cells. Though chlorprozamine prevented infection, it was associated with serious side effects, such as lowered blood pressure, stiffness, and tremors. Therefore, the researchers tested similar antipsychotic drugs and found three that prevented infection without serious side effects. They suspect that other drugs—such as the antihistamine cyproheptadine—may have the same effect on the virus without the side effects of some antipsychotic drugs.

Skeletal muscle could be a source for stem cells that could be applied to the development of therapies aimed at repairing damaged muscle or nerve tissue, according to an article in the November 20 Lancet. Investigators obtained samples of skeletal muscle from 12 adult patients undergoing cardiovascular surgery. They found that the stem cells derived from the muscle tissue could differentiate into astrocytes and neurons, indicating that they were not only able to generate into cells of the same lineage but also into cells with neurogenic properties. The investigators concluded that skeletal muscle might be an alternative tissue source for stem cells for the development of cell-based therapies for myogenic and neurogenic diseases.

The drug indoprofen increases the production of a protein that is key to the survival of nerve cells affected by spinal muscular atrophy, according to a study in the November Chemistry and Biology. After screening 47,000 chemical compounds, investigators chose to test indoprofen’s ability to treat fibroblasts taken from patients with type I spinal muscular atrophy. They found that treatment with indoprofen resulted in a 13% increase in protein production in the fibroblast cells. “While this additional protection wouldn’t cure the disease, it could lessen the severity of the symptoms,” said the researchers. Because indoprofen was withdrawn from pharmacy shelves more than 20 years ago due to reports of serious gastrointestinal reactions, researchers are now looking into ways to modify the drug.

Thyroid hormone may help to reinsulate nerve fibers in the brain and spinal cord of patients with multiple sclerosis (MS), according to a report in the November 16 Proceedings of the National Academy of Sciences. In a rat model, researchers found that thyroid hormone helped oligodendrocyte precursor cells to form new myelin sheaths and protect nerve fibers from deteriorating. However, this effect was observed only if thyroid hormone was given during the acute phase of MS. The investigators said administration of thyroid hormone could be a noninvasive addition to other types of MS therapies.

Activated protein C (APC) seems to counter the harmful effects of tissue plasminogen activator (t-PA), and a combination of the two drugs may offer a new treatment for stroke patients, according to the December Nature Medicine. “t-PA is tremendous at opening up blood vessels, but problems with toxicity diminish the positive effects,” said researchers. t-PA can kill neurons and endothelial cells by accelerating apoptosis. The investigators found, however, that APC countered the harmful effects of t-PA. “Mice that received APC and t-PA had 85% less brain damage from stroke as mice that received t-PA but not APC.” APC also lowered the level of apoptotic cells to pre–t-PA levels. “Perhaps these drugs could be coadministered to give maximum beneficial effect to patients,” said the researchers.

Researchers have found six mutations of the LRRK2 (leucine-rich repeat kinase 2) gene that may be central to the pathogenesis of several neurodegenerative disorders associated with parkinsonism, according to a study in the November 18 Neuron. Among members of two families, six postmortem diagnoses revealed diverse pathologies—“these included abnormalities consistent with Lewy body Parkinson’s disease, diffuse Lewy body disease, nigral degeneration without distinctive histopathology, and progressive supranuclear palsy-like pathology.” The group also noted clinical diagnoses of parkinsonism with dementia or amyotrophy or both.

NR