A vaccine for dementia, new migraine treatment, medical benefit of a party drug, and more
It’s the first week of 2020, the beginning of a new year and a new decade. There’s a lot going on in the field of neurology to start them both, from new research on a possible vaccine for dementia (how great would that be?), to a newly FDA-approved drug for migraines, and a newfound link between hydration and cognitive function. Take a minute and read all about these and many other new findings in this week’s NeuroBrief.
Breaking through the blood—brain barrier? It was only 3 years ago that researchers discovered how to use ultrasound and microbubbles to safely open up the highly selective blood-brain barrier (BBB) in patients with Alzheimer disease. By directing ultrasound waves across focal points that generated microbubbles in the BBB, researchers found they could very precisely open up tiny gaps with very high precision, which then naturally seal themselves within 24 hours. This research is very exciting because it has the potential to help deliver therapies that could previously not reach the brain because of the BBB. There’s the potential with this research to develop ways to use targeted drug delivery to specific brain regions to treat numerous neurological diseases that involve cognitive benefits. A very big deal!
In the News
Stem cells for relapsing MS. The NIH recently announced that it has begun a new clinical trial to compare the use of an experimental stem cell treatment against the best available biologic therapies for severe forms of relapsing multiple sclerosis. Sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the trial will assess the safety, efficacy, and cost-effectiveness of these two approaches.
In many patients with relapsing multiple sclerosis, first- and second-line treatments cannot adequately control their disease. This study—BESt Available Therapy versus autologous hematopoietic stem cell transplant for Multiple Sclerosis (BEAT-MS)—is the first to assess the use of autologous hematopoietic stem cell transplant (AHSCT) in these patients who would otherwise go on to receive treatment with a third-line biologic. AHSCT, however, carries significant risks. Stay tuned for how the research pans out.
Which German neurologist mapped the cerebral cortex into 52 different areas according to histological characteristics?
Using Nissl staining—which shows the location of the cell body of a neuron—Korbinian Brodmann, MD, constructed a detailed map of the human brain by individually identifying neurons in 1909. The 52 areas are known as the Brodmann areas.
Blood screening for dementia? It’s a possibility! Researchers have found that a blood plasma associated with inflammation may be an early warning sign for certain dementias. The marker is plasma soluble CD14 (sCD14), and in two studies, researchers measured sCD14 in the blood of over 4,700 participants (mean ages: 69 and 72 years). In the first study, MRI and cognitive testing were done at years 1 and 7, and participants were screened for dementia over an average of 9 years. In the second, participants were assessed with MRI 3 or 4 years after enrollment and then at 5 years. Researchers discovered that higher sCD14 levels were associated with brain injury, aging, and cognitive decline. Inflammation is known to play a contributing role in many neurological diseases, and neuroinflammatory responses are thought to come into play in many different types of dementia. Still, researchers do not yet understand exactly how this occurs.
Could MRIs predict IQs? Researchers from the Skolkovo Institute of Science and Technology (Skoltech), Moscow, Russia, have found a correlation between the intelligence levels in children and the brain’s anatomy via a prediction model applied to MRIs. They developed this model in response to an international competition organized by the NIH. For the competition, the NIH made available—for the first time ever—data from the Adolescent Brain Cognitive Development study, which contains over 11,000 structural and functional MRI images of children aged 9-10 years. Researchers were tasked with building a predictive model based on these brain images.
Skoltech researchers built a network architecture that allowed for the application of several mathematical models to the data and focused on predicting the intelligence levels of children. When all was said and done, they found that their model was able to predict both the intelligence level and the target variable independent of age, gender, brain size, or MRI scanner used. Although more work needs to be done, wouldn’t it be amazing to think that imaging the brain’s anatomy could actually predict intelligence?
Vaccines don’t cause autism, but dad’s age might. Predicting the risk of autism spectrum disorders (ASD) in future children may be as easy as measuring sperm mutations in the father. Gene-damaging de novo mutation can play a role in at least 10% to 30% of cases of ASD, according to recent studies. This is bad news for older fathers in particular, because the number of mutations increases with age. And—in more bad news—male sperm has been shown to be an important source of such mutations, with the chance of mutations recurring within the same family estimated to be 1% to 3%.
Using deep, whole-genome sequencing, researchers analyzed the sperm of eight fathers of children with ASD for mosaicism—or the presence of multiple, genetically different cellular materials in the same person. They found variants in offspring matched only in the fathers’ sperm, with mutations present in up to 15% of the fathers’ sperm cells. In the future, if this research evolves and can be developed into a clinical test, fathers’ sperm could be key to assessing the risk of ASD recurrence in their future children, as well as in men who haven’t had children yet.
What can’t cannabis do? In a murine model, HU-308—an investigational agent and derivative of cannabis—demonstrated comparable efficacy to amantadine in mitigating the dyskinesias caused by long-term treatment for Parkinson disease. Researchers also found that combining HU-308 and amantadine was more effective than either drug used alone. HU-308 reduces inflammation in the brain and affects the immune cells, which are often involved in neurological disorders. Researchers are hopeful that HU-308 will lead them to new treatment options for Parkinson disease and other neurological disorders.
Molly in the spotlight. MDMA—a mind-altering party drug more commonly known as Ecstasy or Molly—has shown promise in treating mental health conditions that involve problems with empathy and sociability. MDMA is classified as a Schedule I drug, which means it’s illegal. But researchers of a mouse study found that MDMA may have positive effects on increasing sociability, with minimal risks of addiction and other side effects. In the dorsal raphe nucleus, which communicates with the nucleus accumbens, MDMA stimulates neurons to release serotonin, which regulates mood, sexual desire, and social behavior.
When given MDMA, mice were more social at doses of 7.5 mg/kg, a low dose, but not at a lower dose of 2 mg/kg. Compared with placebo-treated mice who “hung out” with their buddies for only 10 minutes, mice treated with this higher dose of MDMA did so for at least 30 minutes. More studies are needed, however, and researchers caution that MDMA should not be used habitually, as it has a slight propensity to cause addiction. Never thought you’d be happy to hear about the social lives of mice, right?
FDA approves new migraine drug of its kind. On Christmas Eve, the FDA approved ubrogepant (Ubrelvy, Allergan USA, Inc.) tablets for the acute treatment of migraine with or without aura. It’s not approved, however, for preventive treatment. Ubrogepant is the first oral calcitonin gene-related peptide receptor antagonist approved for migraine. Efficacy was demonstrated in two randomized, double-blind, placebo-controlled trial in 1,439 adult patients. The most common side effects were nausea, fatigue, and dry mouth, and it’s contraindicated with strong CYP3A4 inhibitors. Your migraine patients will thank you!
New in Patient Management
A vaccine for dementia? Believe it or not, researchers are working to develop an effective vaccine that could remove the brain plaque and tau protein aggregates that are associated with Alzheimer disease. They’ve had recent successes in biogenic mouse models, and hope to move to human clinical trials in the future. Researchers at the Institute for Molecular Medicine and University of California, Irvine, are studying a successful vaccine formulated on an adjuvant that was developed by Professor Nikolai Petrovsky, Flinders University, Adelaide, South Australia. Their latest research focuses on developing a new treatment that removes the accumulation of beta-amyloid plaques and neurofibrillary tangles composed of hyperphosphorylated tau, the combination of which causes neurodegeneration and cognitive decline in Alzheimer disease.
Water: Food for the brain? Being dehydrated—or overhydrated—could affect mental performance, especially in women. Researchers analyzed data from 2,506 participants enrolled in the Nutrition and Health Examination Survey and assessed hydration levels via measurement of serum levels of sodium, potassium, glucose, and urea nitrogen. They also subjected participants to a barrage of cognitive function tests. In the end, they found that when dehydrated and overhydrated, women had poorer cognitive performance.
Furthermore, they found that those who were over- or underhydrated performed the worst in measures of attention, processing speed, and working memory. This association is of particular significance in older individuals, who are not only at greater risk for cognitive problems but also at greater risk for dehydration. The bottom line is this: Proper hydration is good for the body and the mind.
Fragmented sleep? Beware a migraine. Individuals who suffer from fragmented sleep may be at higher risk of having a migraine episode 2 days later, according to a recent study. Although sleep and migraine have been linked for many years, and a lack of good sleep is a known trigger of migraine and tension headaches, researchers sought to study the association a little more deeply (pun intended). Sleep fragmentation is defined as a low sleep efficiency—which is really the amount of time you lay awake in bed trying to sleep. Researchers included 98 adults (mean age: 35 years) who underwent actigraphy measures of sleep (to record sleep patterns in real-time) and kept electronic sleep diaries. All had less than 15 migraine days per month. In the end, fragmented sleep was associated with a higher risk of migraine on the second day after having fragmented sleep—a 39% higher risk.
Should moms taking antiepileptics breastfeed? Infants whose mothers are being treated with antiepileptic drugs (AEDs) are notexposed to high drug levels via breastmilk, according to results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study. Researchers included 351 women with epilepsy and their 345 infants; of these infants, 64% were breastfed. Researchers also measured AED concentrations from blood samples from both mothers and infants at 5 to 20 weeks after birth. They found that AED serum concentrations in breastfed infants were significantly lower than those of the mothers, with about 49% of concentrations less than the lower limit of measurement. Researchers will follow these infants until they’re 6 years old to see what the long-term outcomes may be, but for now, these moms can rest assured that their babies’ exposure to any AEDs is low.
Immunotherapy for glioblastoma just go eaiser. A new approach to delivering immunotherapies to patients with glioblastomas may promote their efficacy. In patients with glioblastoma, such treatments are unusually ineffective, mainly because myeloid-derived suppressor cells (MDSCs) run interference, blocking any good effects. MDSCs can promote immunosuppression, tumor progression, and treatment resistance. Researchers have found that by targeting MDSCs and the chemokine receptors that enable them to infiltrate the areas around glioblastoma tumors, they can achieve better responses to immunotherapies in these patients. In mice without chemokine receptor 2 (CCR2) who developed glioblastomas, MDSCs couldn’t make their way to the tumors to block immunotherapy. In these mice, immune checkpoint inhibitor treatment brought about a strong anticancer immune response, prolonging survival. In mice with normal CCR2, blocking the CCRs brought about similar results.
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Upcoming Medical Meetings
46th Annual Meeting of the Southern Clinical Neurological Society (SCNS) CME, in Naples, FL, January 18-22, 2020
13th Annual Headache Cooperative of the Pacific (HCOP) Winter Conference CME, in Ojai, CA, January 24-25, 2020
12th Annual Symposium on Neurovascular Disease CME, in Santa Monica, CA, January 25, 2020
North American Neuromodulation Society (NANS) Annual Meeting CME, in Las Vegas, NV, January 23-26, 2020