Li Gan, PhD, wants to find treatments to help patients with Alzheimer’s disease. Like most researchers, she’s hit a few major roadblocks.
When researchers like Gan find potential new drugs, it’s useful to test them on human cells to increase the chances that they will benefit patients. Historically, these tests have been conducted in cancer cells, which often don’t match the biology of human brain cells.
“The problem is that brain cells from actual people don’t survive well in a dish, so we need to engineer human cells in the lab,” explained Gan, senior investigator at the Gladstone Institutes. “But, that’s not as simple as it may sound.”
Many scientists use induced pluripotent stem cells (iPSCs) to address this issue. IPSCs are made by reprogramming skin cells or blood cells to become stem cells, which can then be transformed into any type of cell in the body. Gan uses iPSCs to produce brain cells, such as neurons or glial cells, because they are relevant to neurodegenerative disease.
Human brain cells derived from iPSCs offer great potential for drug screening. Yet, the process for producing them can be complicated, expensive, and highly variable. Many of the current methods produce cells that are heterogeneous, or different from one another, and this can lead to inconsistent results in drug screening. In addition, producing a large number of cells is very costly, so it’s difficult to scale up for big experiments.
A new platform developed in Gan’s lab will now allow scientists to overcome these constraints
A New Technique Is Born
“I came across a new method to produce iPSCs that was developed at Stanford,” said Michael Ward, MD, PhD, a former staff scientist in Gan’s lab who is now an investigator at the National Institutes of Health. “I thought that if our team could find a way to simplify and better control that approach, we might be able to improve the way we engineer human brain cells in the lab.”
Ward and his colleague Chao Wang, PhD, discovered a way to manipulate the genetic makeup of cells to produce thousands of neurons from a single iPSC. This meant that every engineered brain cell was now identical.
“I was truly motivated by our initial results,” said Gan, who is also a professor of neurology at UC San Francisco. “I had observed too much variability using the traditional methods, which made reproducing experiments quite problematic. So, the ability to produce homogeneous human brain cells was very exciting.”
The team further improved the technique to create a simplified, two-step process. This allows scientists to precisely control how many brain cells they produce and makes it easier to replicate their results from one experiment to the next.
Their technique also greatly accelerates the process. While it would normally take several months to produce brain cells, Gan and her team can now engineer large quantities of them within 1 or 2 weeks, and have functionally active neurons within 1 month.
The researchers realized this new approach had tremendous potential to screen drugs and to study disease mechanisms. To prove it, they tested it in their own research.
They applied their technique to produce human neurons by using iPSCs. Then, they developed a drug discovery platform and screened 1,280 compounds. Their goal is to identify the compounds that could lower levels of the protein tau in the brain, which is considered one of the most promising approaches in Alzheimer’s research and could potentially lead to new drugs to treat the disease.
“We showed that we can engineer large quantities of human brain cells that are all the same, while also significantly reducing the costs,” said Wang, Gladstone postdoctoral scholar. “This means our technology can easily be scaled up and can essentially be used to screen millions of compounds.”
A Powerful Tool for the Entire Scientific Community
“We have developed a cost-effective technology to produce large quantities of human brain cells in two simple steps,” summarized Gan. “By surmounting major challenges in human neuron-based drug discovery, we believe this technique will be adopted widely in both basic science and industry.”
Word of this useful new technology has already spread, and people from different scientific sectors have come knocking on Gan’s door to learn about it. Her team has shared the new method with scores of academic colleagues, some of whom had no experience with cell culture. So far, they all successfully repeated the two-step process to produce their own cells and facilitate scientific discoveries.
Details of this new technique were published on October 10, 2017, in the scientific journal Stem Cell Reports.
With some of the roadblocks out of the way, Gan hopes more discoveries will soon help the millions who suffer from Alzheimer’s disease and related conditions.
Learn more: Growing Human Brain Cells in the Lab
The Latest on: Drug discovery
- BridGene Biosciences Announces Presentations at Hippo Pathway Targeted Drug Development Summiton May 19, 2022 at 5:33 am
BridGene is a biotechnology company focused on discovering and developing innovative small molecules that drug traditionally undruggable targets, providing new paths to treat diseases. By using its ...
- Drug Discovery Services Market Industry Key Players, Trends, Sales, Supply, Demand, Analysis and Forecast to 2025on May 18, 2022 at 10:44 pm
Snapshot The global drug discovery services market is thriving on account of the rising impetus given to research ...
- UTMB drug discovery partnership awarded $56 million granton May 18, 2022 at 3:47 pm
A $56 million grant from the National Institute of Allergy and Infectious Diseases will establish an Antiviral Drug Discovery (AViDD) Center for Pathogens of Pandemic Concern at the University of ...
- PostEra spearheads AI-driven drug discovery collaboration to develop antiviral therapeutics with initial $68M in NIH fundingon May 18, 2022 at 1:50 pm
BOSTON, May 18, 2022 /PRNewswire/ -- PostEra, a biotechnology company specializing in machine learning for preclinical drug discovery, today announced a multi-year collaboration with the National ...
- Artificial intelligence makes a splash in small-molecule drug discoveryon May 17, 2022 at 5:34 am
Companies applying artificial intelligence tools in small-molecule drug discovery have recently attracted substantial financing and a multitude of large pharma partners.
- BenevolentAI achieves third milestone in its AI-enabled drug discovery collaboration with AstraZenecaon May 16, 2022 at 10:00 pm
Second novel target for idiopathic pulmonary fibrosis was discovered using BenevolentAI's drug discovery platform and selected for AstraZeneca's drug development portfolioA total of three targets have ...
- Fujitsu and RIKEN start joint research on next-generation IT drug discovery technology using the supercomputer Fugaku and simulation integrated AIon May 16, 2022 at 7:58 pm
Fujitsu Limited and RIKEN today launched a joint research project on next-generation IT drug discovery technology utilizing the supercomputer Fugaku(1), aiming to accelerate DX (digital transformation ...
- Sosei Heptares and Kallyope Enter Collaboration to Identify and Validate Novel Gastrointestinal GPCR Targets for Drug Discoveryon May 16, 2022 at 6:30 pm
Collaboration is part of Sosei Heptares’ Target Identification and Validation (TIV) strategy to leverage multiple sophisticated technologies that drive creation of new drug discovery programs in key ...
- Drug-discovery pioneer Verseon delivers breakthrough once predicted by Steve Jobson May 16, 2022 at 7:56 am
Apple's visionary founder Steve Jobs once said, "The biggest innovations of the 21st century will be at the intersection of biology and technology." Silicon Valley-based Verseon now sees itself at ...
- Insights into malaria parasites strengthen drug discovery pipelineon May 16, 2022 at 6:57 am
Revolutionary 3D images have enabled researchers to understand how new anti-malaria compounds kill malaria parasites, paving the way for the next generation anti-malarial treatments. Malaria ...
via Google News and Bing News