Breaking News
December 11, 2018 - Ezogabine treatment reduces motor neuron excitability in ALS patients, study shows
December 11, 2018 - One implant, two prices. It depends on who’s paying.
December 11, 2018 - Standardizing feeding practices improves growth trends for micro-preemies
December 11, 2018 - COPD Tied to Obesity in Male, Female Never-Smokers
December 11, 2018 - Flossing: Information for Caregivers
December 11, 2018 - Does breastfeeding hormone protect against type 2 diabetes?
December 11, 2018 - Krystal 2000 microplate design improves fluorescence and luminescence measurement
December 11, 2018 - FDA clears mobile medical app to help increase retention in recovery program for opioid use disorder
December 11, 2018 - Overcoming Challenges in High-Speed Centrifugation Experiments
December 11, 2018 - Study shows link between neighborhoods’ socioeconomic status and dietary choices
December 11, 2018 - Lower BMI before obesity surgery predicts greater post-operative weight loss, study finds
December 11, 2018 - Obesity May Be Driving Rise in Uterine Cancers
December 11, 2018 - Antioxidants may prevent cognitive impairment in diabetes
December 11, 2018 - Researchers identify potential diagnostic tool for Alzheimer’s disease
December 11, 2018 - Oral cancer prognostic signature identified
December 11, 2018 - How Can I Find Out What Caused My Miscarriage?
December 11, 2018 - Novel personalized medicine tool for assessing inherited colorectal cancer syndrome risk developed
December 11, 2018 - Study uncovers 11 new genes associated with epilepsy
December 11, 2018 - Filling research gaps could help develop more disability-inclusive workplaces
December 11, 2018 - Cartilage tissue engineering brings good news for patients with cartilage defects
December 11, 2018 - Novel 3D printing workflow helps predict leaky heart valves
December 11, 2018 - Imagination can help overcome fear and anxiety-related disorders, shows study
December 11, 2018 - Are caries linked to political regime?
December 11, 2018 - Leader in Diabetes Clinical Trials Wins Naomi Berrie Award
December 11, 2018 - Scientists discover cellular mechanism that triggers pneumonia in humans
December 11, 2018 - Increasing mental health problems related to drug use in over 55’s
December 11, 2018 - High-intensity interval exercise could help combat cognitive dysfunction in obese people
December 11, 2018 - Annual flu shot can save lives of heart failure patients
December 11, 2018 - Researchers compare health outcomes for VA and non-VA hospitals
December 11, 2018 - Recommendations Developed for Psoriatic Arthritis Treatment
December 11, 2018 - Genetic analysis links obesity with diabetes, coronary artery disease
December 11, 2018 - Study shows that having genetic information can affect how the body responds
December 11, 2018 - UNAIDS Report: 9 Million Are Likely HIV Positive And Don't Know It
December 11, 2018 - Lund University researchers succeed in obtaining dendritic cells by direct reprogramming
December 11, 2018 - Breast tumors recruit bone marrow cells to boost their growth, study reveals
December 11, 2018 - Updated breast cancer screening guideline highlights importance of shared decision-making
December 11, 2018 - EHR-related stress associated with physician burnout
December 11, 2018 - AHA: 12-Year-Old Heart Defect Survivor Inspires NFL Player’s Foundation
December 11, 2018 - Breast cancer patients who take heart drug with trastuzumab have less heart damage
December 11, 2018 - Providing aid to those humans – and animals – affected by the California fires
December 11, 2018 - Even without proof, CBD is finding a niche as a cure-all
December 11, 2018 - Drawing leads to better memory than writing
December 11, 2018 - Researchers report novel findings on plant hormone
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
December 10, 2018 - DDT in Alaskan fish shown to increase risk of cancer
December 10, 2018 - Laws to curb use of cell phones have greatly reduced fatalities for motorcyclists
December 10, 2018 - Argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia
December 10, 2018 - University of Maryland doctors treat first breast cancer patients with GammaPod radiotherapy
December 10, 2018 - The heartbeat seat: Demoing new well-being technologies in a car
December 10, 2018 - Leading Cancer Researcher to Direct Herbert Irving Comprehensive Cancer Center
December 10, 2018 - Researchers explore how glial cells develop in the brain from neural precursor cells
December 10, 2018 - Study compares pain-related diagnoses in First Nations and non-First Nations children, youth
December 10, 2018 - Experts address sleep disorders following traumatic brain injury
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Smart life-collar could save lives of young children
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Episodic memory tests help in predicting brain atrophy and Alzheimer’s disease
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
Fruit fly research leads to potential drug for debilitating diseases caused by parasitic worms

Fruit fly research leads to potential drug for debilitating diseases caused by parasitic worms

image_pdfDownload PDFimage_print

River blindness and elephantiasis are debilitating diseases caused by parasitic worms that infect as many as 150 million people worldwide. They are among the “neglected tropical diseases” for which better treatments are desperately needed. But they were far from the mind of cell biologist William Sullivan when he began studying the microbial parasite Wolbachia, best known for its extraordinary effects on the many insect species it infects.

Sullivan, a professor of molecular, cell, and developmental biology at UC Santa Cruz, has spent much of his career studying the basic biology of the cell cycle in the fruit fly Drosophila. To study the interactions of Wolbachia with its insect hosts, he created a stable cell line of Wolbachia-infected Drosophila cells which he could grow indefinitely in the laboratory. This cell line turned out to be an invaluable tool for researchers seeking new drugs to treat river blindness and related diseases.

That’s because the filarial nematodes that cause these diseases are actually dependent on Wolbachia living within their cells. Kill the Wolbachia, and the worms die.

“The insects would rather not have the Wolbachia infection–it manipulates their reproductive biology and does all these things to promote its own survival. But the worms can’t live without it,” Sullivan said.

Sullivan’s lab worked with the UC Santa Cruz Chemical Screening Center to develop an automated screening assay that could be used to test thousands of compounds for the ability to kill Wolbachia without harming the Drosophila host cells. Sullivan’s team screened nearly 5,000 compounds, of which 40 were active against Wolbachia, including several related to a compound (albendazole) already used to treat filarial nematode infections. Their findings, published in 2012, showed that albendazole and its metabolites target both the worms and the Wolbachia.

Albendazole and other existing treatments all have shortcomings, however, and Sullivan soon realized that he did not have the funding or the resources to pursue the search for better treatments any further. “At that point, we were stuck, because we didn’t have the resources for a full-scale drug discovery effort,” he said.

Then he found out about the California Institute for Biomedical Research (Calibr), a nonprofit organization dedicated to developing medicines for unmet medical needs. With funding from the Bill & Melinda Gates Foundation, Calibr works with external partners, including academic researchers, and provides drug discovery expertise and infrastructure.

Sullivan ended up giving a seminar on his Wolbachia work at Calibr’s facilities in La Jolla, which led to an ongoing collaboration. One of his graduate students, Pamela White, worked with Calibr scientists to train them on the screening assay. Ultimately, Calibr tested more than 300,000 compounds with an optimized version of the assay for high-throughput screening.

Sullivan’s lab also helped develop a secondary assay for assessing the effectiveness of promising compounds against Wolbachia in filarial nematodes. That was important because the Wolbachia species that infect Drosophila are significantly different from those that infect the worms. “The cell-based assay is not a perfect assay, but it gives you a starting point,” he said.

Using Sullivan’s assays, Calibr has identified a lead compound, improved its performance, and tested it in animals infected with filarial worms. The compound is currently in preclinical development, the stage at which scientists assess safety and tolerability in animal models. If all goes well, the next step will be phase I clinical trials in humans.

“It’s a good example of why we do basic research. You never know where it will lead,” Sullivan said.

He admits that transferring his assays to Calibr felt a little uncomfortable at first. “At the time, I thought of it as my thing. But now that I see what they’ve done with it, I’ve realized that our contribution was part of a much larger effort and this handoff happened at the perfect time,” Sullivan said.

A drug that targets Wolbachia has several advantages over one that targets the worms directly. Research over the past decade has shown that much of the harm caused by filarial nematode infections results from the immune system’s inflammatory response to Wolbachia released by the worms. Eliminating the Wolbachia before the worms die reduces that harmful immune response and leads to a slow death of the worms.

The antibiotic doxycycline has been tested in clinical trials and shown to be an effective treatment for elephantiasis (lymphatic filariasis) when given in daily doses for at least four weeks. But a more potent drug with a shorter course of treatment would be much more practical for use in the developing countries where these diseases are prevalent, Sullivan said.

Meanwhile, Sullivan has begun teaching a course on neglected tropical diseases at UC Santa Cruz. He said the students are amazed to learn how common these diseases are compared to how much research is done on them. “One in six people on this planet suffer from a disease that most people in this country have never heard of,” he said. “It’s been really eye-opening, for me and for the students.”

Sullivan’s lab has also continued to study Wolbachia infections in Drosophila, returning to the project for which the infected cell line was initially created. Using the same automated screening assay used in the drug discovery project, Sullivan’s team screened the Drosophila genome to find genes that either suppress or increase the proliferation of Wolbachia in host cells. The study, published in 2017, identified several key biological pathways that Wolbachia alters in host cells to maintain infections. The findings may explain why Wolbachia infection makes insects resistant to RNA viruses, a feature that is now being exploited in efforts to combat the spread of Zika, dengue, and other mosquito-transmitted diseases.

“There are so many amazing Wolbachia stories, and we still have a lot to learn about it,” Sullivan said.​

Source:

https://news.ucsc.edu/2018/07/river-blindness.html

Tagged with:

About author

Related Articles