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
[google_news title=”” keyword=”drug discovery” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]- Two-punch treatment delivers blood cancer knockout: Study shows drug combo eradicates cancer cells in lab-based testson May 1, 2024 at 6:47 am
The WEHI research team paired venetoclax, a current standard-of-care anti-cancer drug for AML, with a STING agonist, an emerging class of immunotherapy drugs. Venetoclax was based on a landmark ...
- Bloodsucking fly behind ‘new drug discovery’on May 1, 2024 at 12:11 am
Researchers at the University of Sydney have discovered a potentially “game-changing” new drug capable of preventing blood clots and fatal bleeding during surgery – thanks to the bloodsucking African ...
- NYC-based AI drug discovery company moves HQ to Cambridgeon April 30, 2024 at 6:57 am
If you are not in Boston, you are not in biotech, in my opinion,” said the founder of Insilico, a 10-year-old AI drug discovery company that's moving its headquarters from New York to Massachusetts.
- Xaira Launches with $1 Billion to Pioneer AI-Driven Drug Discoveryon April 28, 2024 at 11:36 pm
Xaira Therapeutics, an AI drug discovery startup, recently launched with a remarkable $1 billion funding, backed by prominent investors like ARCH Venture Partners and Foresite Labs. The company, led ...
- A Pharmaceutical Company is Working to Speed Up the Drug Development Process with AIon April 28, 2024 at 9:50 pm
Algorae Pharmaceuticals is finding ways to revamp its process of drug development from cost saving and speed to timeline of drug research and delivery by ...
- Drug Discovery Services Market To Reach USD 75.3 Billion By 2032, Says DataHorizzon Researchon April 27, 2024 at 6:31 am
The drug discovery services market size was valued at USD 20.8 Billion in 2023 and is expected to reach a market size of USD 75.3 Billion by 2032 at a CAGR of 15.4%.Fort Collins, Colorado, April 27, ...
- This Biotech Startup Aims To Speed Up Drug Testing On Animalson April 26, 2024 at 3:29 am
Gordian Biotechnology’s platform allows for potentially hundreds of gene therapies to be tested in an animal at the same time — without harming it.
- Using Explainable AI To Ensure Drug Discovery Safetyon April 25, 2024 at 5:00 pm
Can you discuss the significance of this for drug discovery/ development? SW: Safety is a huge cause of failure, 56% of projects are failing from preclinical trials onwards due to safety. Yet, when we ...
- A shortcut for drug discovery: Novel method predicts on a large scale how small molecules interact with proteinson April 25, 2024 at 11:00 am
For most human proteins, there are no small molecules known to bind them chemically (so-called "ligands"). Ligands frequently represent important starting points for drug development but this ...
- The Difference Is the Data: Drug Discovery’s AI Revolutionon April 25, 2024 at 4:00 am
New data-intensive platforms continue to leverage artificial intelligence tools for improved speed and failure rate reductions for drug discovery.
via Google News and Bing News