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
- K9 makes drug discovery at Philadelphia Int'l Airporton January 10, 2020 at 3:29 pm
PHILADELPHIA (WPVI) -- Nearly 500 grams of marijuana was detected by a U.S. Customs and Border Protection dog team at Philadelphia International airport.. Officials say K9 Dasha caught the marijuana ...
- 23andMe has sold the rights to develop a drug based on its users’ DNAon January 10, 2020 at 10:30 am
The deal for the drug, which is being investigated as a potential treatment for inflammatory diseases, is with Spanish pharmaceutical company Almirall. “This is a seminal moment for 23andMe,” Emily ...
- In silico analysis of alternative splicing on drug-target gene interactionson January 10, 2020 at 2:25 am
Identifying and evaluating the right target are the most important factors in early drug discovery phase. Most studies focus on one protein ignoring the multiple splice-variant or protein-isoforms, ...
- Drug Discovery Market 2020: Major Manufacturers Production and Sales Market Comparison Analysis and Forecast By 2025on January 9, 2020 at 10:11 pm
Drug Discovery Market report provides a comprehensive landscape of the business, correct market estimates and forecast split by product, application, technology, region and end-use. with growth trends ...
- Lilly launches new robotic drug discovery laboratoryon January 9, 2020 at 1:18 pm
Eli Lilly (LLY +1.7%), in collaboration with lab automation developer Strateos, announces a new San Diego-based robotic laboratory, called the Lilly Life Sciences Studio Lab, designed to accelerate ...
- Bayer and Exscientia partner to leverage AI-powered drug discoveryon January 9, 2020 at 7:11 am
The partnership will see AI-powered drug discovery specialists Exscientia become the first UK company to partner with Bayer for this purpose. The two parties have agreed on targets for three upcoming ...
- Evotec and Bayer Announce New Alliance Focusing on Drug Discovery for Polycystic Ovary Syndrome With Novel Targets From Celmatixon January 9, 2020 at 6:16 am
In this research collaboration, Evotec is responsible for medicinal chemistry, in vitro and in vivo pharmacology, in addition to its broad development capabilities and expertise, while Celmatix ...
- Drug Discovery Informatics Market 2020 Overview, Latest Analysis and Future Forecast By 2025 – Market Research Engineon January 9, 2020 at 3:51 am
New York, January 09, 2020: The report covers detailed competitive outlook including the market share and company profiles of the key participants operating in the global market. Key players profiled ...
- Global Drug Discovery Market 2019-2027 - Rising Demand for Specialty Medicineson January 9, 2020 at 1:43 am
Dublin, Jan. 09, 2020 (GLOBE NEWSWIRE) -- The "Global Drug Discovery Market 2019-2027" report has been added to ResearchAndMarkets.com's offering. The global drug discovery market is estimated to grow ...
- Deep Genomics Gathers $40 Million for AI-Based Drug Discoveryon January 7, 2020 at 7:29 pm
Deep Genomics has raised $40 million in venture capital to put treatments discovered through its artificial intelligence-based drug-discovery platform to the test in human studies.
via Google News and Bing News