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
- CETSA HT in early drug discovery through screening against B-Raf and PARP1 on December 13, 2018 at 5:04 pm
We allow third-party companies to serve ads and/or collect anonymous information. These companies may use non-personally identifiable information (browser type, time and date) in order to provide adve... […]
- Drug Discovery Informatics Market - Technology, Trends, Development, Key Manufacturers Analysis and Forecast to 2025 on December 13, 2018 at 12:44 pm
Some of the key players influencing the market are PerkinElmer, Inc., Schrödinger, LLC, Certara, L.P., Infosys Limited, IBM, Collaborative Drug Discovery, Inc., Jubilant Life Sciences Ltd ... […]
- X-Chem, Almirall forge dermatology-focused drug discovery alliance on December 13, 2018 at 3:08 am
Under the terms of the agreement, X-Chem will utilize its industry-leading DNA-encoded library (DEX) screening platform and proprietary informatics tools to search for novel hits for Almirall targets. ... […]
- Killing the liver-stage malaria parasite with baculovirus: a drug discovery approach on December 12, 2018 at 7:45 am
A proportion of P. vivax sporozoites differentiate to a hypnozoite form that ultimately reactivates and proliferates leading to a blood-stage relapse. The hypnozoites are not eradicated by ... […]
- Almirall and X-Chem Announce Dermatology-Focused Drug Discovery Collaboration on December 12, 2018 at 4:15 am
X-Chem, Inc. (X-Chem), a privately held biotechnology company applying its innovative drug discovery platform to the generation of novel small molecule therapeutics, announced today a drug discovery p... […]
- Schrödinger, TB Alliance collaborate to advance tuberculosis drug discovery on December 12, 2018 at 3:45 am
Schrödinger and TB Alliance have entered into a three-year research collaboration to enhance the development of next-generation tuberculosis (TB) treatments by leveraging Schrödinger’s advanced comput... […]
- Schrödinger and TB Alliance Announce Collaboration to Accelerate Tuberculosis Drug Discovery on December 11, 2018 at 3:01 am
NEW YORK--(BUSINESS WIRE)--Dec 11, 2018--Schrödinger and TB Alliance today announced a three-year research collaboration to speed the development of next-generation tuberculosis (TB) treatments by lev... […]
- HitGen and Mitsubishi Tanabe Pharma Enter DNA-Encoded Library Based Innovative Drug Discovery Research Collaboration on December 10, 2018 at 4:59 pm
HitGen Ltd announced that the company has entered into a drug discovery research collaboration with Mitsubishi Tanabe Pharma Corporation (president and ceo:Masayuki Mitsuka)(headquarters:Osaka)(headqu... […]
- Insilico Medicine to showcase its AI Engine for Future Drug Discovery at the 2018 Future Tech Forum on December 10, 2018 at 9:52 am
IMAGE: Artur Kadurin, Chief AI Officer and CEO of Insilico Taiwan presents "AI in Drug Discovery Creates the Best Era of Precision Medicine " at the 2018 Future Tech Forum. view more Monday, December ... […]
- Reinventing Drug Discovery and Development for Military Needs on December 10, 2018 at 6:00 am
Flying at 50,000 feet, diving deep in the ocean, or hiking for miles with gear through extreme climates, military service members face conditions that place unique burdens on their individual physiolo... […]
via Google News and Bing News