Nav: Home

New platform for roundworms could speed up drug delivery

October 11, 2016

Researchers in the Cockrell School of Engineering at The University of Texas at Austin have developed the first large-scale in vivo drug discovery platform using a whole animal model that could speed up scientific research and more accurately assess the effectiveness of new drugs in the treatment of neurodegenerative diseases.

Professor Adela Ben-Yakar and her team of postdocs and graduate students -- Sudip Mondal, Evan Hegarty, Christopher Martin, Sertan Kutal Gökçe and Navid Ghorashian -- describe their new platform in a study published in the journal Nature Communications on Oct. 11.

The team believes their platform will allow researchers and pharmaceutical companies to undertake image-based analysis of thousands of live, 1-millimeter-long roundworms, called Caenorhabditis elegans (C. elegans), simultaneously and at the speed and cost of in vitro cell-based platforms.

Ben-Yakar, a researcher in the Departments of Mechanical and Biomedical Engineering, led the design of the new platform, which takes the form of a cellphone-size chip that can immobilize and analyze small animal models using a high-powered microscope. The platform is similar to screening platforms for cells, but it can screen a whole organism made of multiple cells by immobilizing thousands of them inside micro-traps to prevent their natural movement. In addition, the platform can automatically understand data using image analysis software, which was also developed by the researchers. This information can help determine whether a drug is effectively treating a disease in the roundworms.

The researchers' microfluidic device is designed to simultaneously image approximately 3,600 roundworms at high resolutions and high speeds, ranging from 12 to 16 minutes. Today's conventional platforms can image only a few animals within such a short time. The device also has the ability to assess the efficacy of many different drug compounds at once. Whereas other microfluidic platforms used today are capable of analyzing only one drug compound at a time, the researchers' new platform can assess 96.

The roundworms, which are desirable in the study of neurodegenerative diseases because they have full nervous systems and a diverse group of neurons, are also the first multicellular organism to have a completely sequenced genome. Approximately one-third of C. elegans' genes are the same as disease-causing genes in humans.

"The C. elegans are thousands of times bigger than cells, so now that we have developed a way to capture and immobilize so many of them so quickly, we can determine much more information about the efficacy of drugs in a whole organism rather than the limited information that is derived when we used isolated individual cells," Ben-Yakar said.

What sets the chip apart from existing platforms is that it is capable of high-throughput screening, the study of thousands to hundreds of thousands of compounds in a rapid and very high-resolution manner, and high-content fluorescence screening, which allows for a faster yet more in-depth analysis of the animals' phenotype.

Made of a flexible polymer, the microfluidic chip contains 96 wells for receiving drug-treated animals. Underneath each well are special microchannels that can trap 40 roundworms. A tapered design squeezes the C. elegans into microchannels in a flat orientation that can be more easily imaged. The microfluidic chip then relies on a gasket system that applies pressure to the chambers to immobilize the roundworms.

"This proof-of-principle study opens the door to using this technology to identify and develop treatments for some of the most intractable human diseases," said Anne Hart, a professor of neuroscience at Brown University who has followed the development of the chip.

To demonstrate the efficiency of their patent-pending device, the team analyzed approximately 1,000 drugs approved by the Food and Drug Administration aimed at treating the protein aggregation found in various neurodegenerative diseases, including Huntington's disease. In doing so, they were surprised to find a potential drug that is particularly effective at treating Huntington's.

"Four of the drugs we tested were effective at treating a protein aggregation model that is directly related to Huntington's, and one of these drugs became even more effective at increased doses without causing toxicity," Ben-Yakar said.

Although the microfluidic device is a prototype, Ben-Yakar's startup company, Newormics, is working to develop a design for a commercial product that could be cheaply and easily manufactured.
-end-
This work received funding from the National Institutes of Health (NIH) Director's Transformative Award, National Institute on Aging (NIH/NIA R01).

University of Texas at Austin

Related Neurodegenerative Diseases Articles:

Researchers identify link between birth defect and neurodegenerative diseases
A new study has found a link between neurological birth defects in infants commonly found in pregnant women with diabetes and several neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases.
High school football players, 1956-1970, did not have increase of neurodegenerative diseases
A Mayo Clinic study published online today in Mayo Clinic Proceedings found that varsity football players from 1956 to 1970 did not have an increased risk of degenerative brain diseases compared with athletes in other varsity sports.
Researchers reveal how neurodegenerative diseases spread through the brain
Synapses, the place where brain cells contact one another, play a pivotal role in the transmission of toxic proteins.
Untangling a cause of memory loss in neurodegenerative diseases
In mice genetically engineered to mimic aspects of human tauopathy disorders, the researchers restored some of the learning and memory deficits by blocking caspase-2 activity, which suggests that some of the cognitive loss seen in tauopathies might be reversible.
New impetus for treatment neurodegenerative diseases
Twenty years ago, tumor necrosis factor (TNF) seemed a promising target in the treatment of brain diseases like multiple sclerosis or Alzheimer's Disease.
More Neurodegenerative Diseases News and Neurodegenerative Diseases Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...