UTSW Research: Mosquito saliva and malaria, brain tumors, and more
Studies look at link between pest’s internal clock and deadly disease, a promising glioblastoma treatment, and Alzheimer’s agitation
Female mosquito salivary glands could unlock key to malaria transmission
Malaria, responsible for hundreds of thousands of deaths each year worldwide, is caused by a parasite transmitted through the salivary glands of female Anopheles mosquitoes. Understanding the biology of these tissues is critical to developing new treatments for the disease, found mostly in tropical countries. Mosquitoes have an internal 24-hour clock that controls a variety of behaviors, including pheromone production, swarming, and mating. However, it has been unknown whether their salivary glands operate on a cyclic daily schedule.
To answer this question, researchers including Joseph Takahashi, Ph.D., Chair and Professor of Neuroscience at UT Southwestern Medical Center and an Investigator in the Peter O’Donnell Jr. Brain Institute, examined gene activity in Anopheles salivary glands. According to their findings, reported in Nature Microbiology, about half of the mosquitoes’ salivary gland genes had rhythmic expression, particularly those important for efficient feeding, such as genes that make anticlotting proteins. The researchers also found that the mosquitoes preferred to feed at night, with the blood volume they ingested varying cyclically throughout the day.
Additionally, genes of the parasites living in Anopheles salivary glands had cyclic differences in activity, especially those involved in parasite transmission. The authors suggest the internal clocks of the parasite, mosquito, and mammalian host play an important role in successful malaria infection.
Study senior author Filipa Rijo-Ferreira, Assistant Professor of Infectious Diseases and Vaccinology at the University of California, Berkeley, is a former postdoctoral researcher in the Takahashi Lab at UTSW.
Nanoparticles extend glioblastoma survival in phase one trial
Despite decades of research to develop effective treatments, the median survival for glioblastoma – the most common malignant primary brain tumor in adults – is just 15-18 months after diagnosis. One reason for this grim statistic is that these tumors invariably recur despite aggressive, multimodality treatments. Although traditional radiation treatments can delay recurrence and extend survival, they often damage healthy brain tissue, negatively affecting quality of life. Preclinical research has suggested radiation-emitting nanoparticles targeting tumor-containing regions through convection enhanced delivery (CED), bypassing the blood-brain barrier, could effectively treat these tumors.
In a phase one clinical trial reported in Nature Communications, two researchers from UT Southwestern and their colleagues showed this strategy was safe and effective. The team worked with 21 patients at medical centers, including UTSW, who had recurrent glioblastoma. They were divided into six groups, each of which received a different dose of radiation-emitting nanoparticles through CED. Patients who received the highest doses had tolerable side effects and lived an average of 17 more months after treatment, significantly longer than expected for patients with recurrent glioblastoma. The authors suggest this strategy shows promise for improving treatments for these patients.
UTSW researchers who contributed to this study are Toral Patel, M.D., Associate Professor of Neurological Surgery, and Michael Youssef, M.D., Assistant Professor of Neurology. Drs. Patel and Youssef are members of the O’Donnell Brain Institute and the Harold C. Simmons Comprehensive Cancer Center at UTSW.
Alternate antidepressant not effective for Alzheimer’s agitation
Up to 60% of people with Alzheimer’s disease experience agitation, a symptom that can be a significant burden for caregivers. Nondrug treatments are recommended as first-line interventions. Citalopram, a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for anxiety and depression, has shown promise for treating Alzheimer’s-induced agitation in patients whose symptoms don’t respond to other therapies. However, this drug has been linked to cardiac and cognitive risks. More specifically, citalopram consists of two compounds that are mirror images, R- and S-citalopram, and it is thought that the R-compound is linked to these risks.
Hoping to reap the same benefits without these risks, researchers in the U.S. and Canada evaluated the S-compound on its own, an available SSRI called escitalopram, in a phase three clinical trial. Results reported in Nature Medicine by Tarek Rajji, M.D., Chair and Professor of Psychiatry and in the O’Donnell Brain Institute at UT Southwestern, and colleagues showed that escitalopram was not effective in treating Alzheimer’s agitation. The drug also was associated with significant side effects including falls, diarrhea, and heart problems.
The authors suggest that citalopram should remain the preferred SSRI for treating Alzheimer’s-related agitation.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.