Oct 162017
 

via Medical Xpress

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
  • Seminar on drug discovery, design and delivery
    on February 21, 2018 at 9:59 am

    The Department of Biosciences, Mangalore University, which is currently under the Government of India UGC's Special Assistance Program (SAP) and under the DST-Fund for Improvement of Science and Technology Infrastructure (FIST), will organise a two-day ... […]

  • Stanford Drug Discovery Conference set for April 23-24
    on February 21, 2018 at 7:43 am

    The two-day conference at Stanford will bring together experts from academia, industry and government to discuss drug policy, research and business opportunities. Registration is open for the 2018 Stanford Drug Discovery Conference, which will take place ... […]

  • Organs on a chip speeding drug discovery, development
    on February 21, 2018 at 1:21 am

    AUSTIN, Texas – Organs on a chip that recreate living human biology are poised to move into mainstream drug discovery and development, complementing, and eventually superseding, cell culture and animal models in preclinical safety and efficacy studies. […]

  • Collaborative Systems for Drug Discovery, with Peter Harris
    on February 17, 2018 at 8:49 pm

    In this episode, Abate interviews Peter Harris from HighRes Biosolutions about automation in the field of drug discovery. At HighRes Biosolutions they are developing modular robotic systems that work alongside scientists to automate laboratory tasks. […]

  • HemaCare and Charles River Laboratories Announce Strategic Partnership to Accelerate Drug Discovery and Development
    on February 15, 2018 at 9:00 pm

    (Los Angeles, CA – February 6, 2018) HemaCare Corporation (OTCBB: HEMA), a global leader in the customization of human-derived biological products and services for biomedical research and cell therapy, and Charles River Laboratories International, Inc ... […]

  • OWKIN secures $11m to scale AI-driven drug discovery platform
    on February 15, 2018 at 4:36 am

    OWKIN recently completed an $11 million Series A funding round, bringing its total funds raised to $13.1m in the last year. The company’s goal is to enable researchers to use artificial intelligence (AI) to answer questions and increase their knowledge ... […]

  • Certara Launches Version 10 of D360, Its Industry-leading Drug Discovery Informatics Platform
    on February 14, 2018 at 3:53 pm

    Certara®, the global leader in model-informed drug development and regulatory science, today announced the launch of version 10 of D360™, its data informatics platform for discovery scientists. D360 is a self-service data access, integration and ... […]

  • Drug Discovery Technology Market to Reach $85.8B in 2022
    on February 13, 2018 at 12:11 pm

    WELLESLEY, Mass., Feb. 13, 2018 (GLOBE NEWSWIRE) — In recent years, the drug discovery market has seen rapid progress with the potential to reach $85.8 billion in 2022, growing at a compound annual growth rate of 9.4% from 2017-2022. The BCC Research ... […]

  • New type of antibiotic discovered in soil in breakthrough for fight against drug-resistant superbugs
    on February 13, 2018 at 2:18 am

    Dr Alderwick, who is director of the Birmingham Drug Discovery Facility as well as a lecturer at Birmingham University, said work by university teams, like the Rockefeller group and his own team, will play a larger role in future antibiotic discovery ... […]

via Google News and Bing News

Other Interesting Posts

Leave a Reply

%d bloggers like this: