A simple drug cocktail that converts cells neighboring damaged neurons into functional new neurons could potentially be used to treat stroke, Alzheimer’s disease, and brain injuries.
A team of researchers at Penn State identified a set of four, or even three, molecules that could convert glial cells—which normally provide support and insulation for neurons—into new neurons. A paper describing the approach appears online in the journal Stem Cell Reports on February 7, 2019.
“The biggest problem for brain repair is that neurons don’t regenerate after brain damage, because they don’t divide,” said Gong Chen, professor of biology and Verne M. Willaman Chair in Life Sciences at Penn State and leader of the research team. “In contrast, glial cells, which gather around damaged brain tissue, can proliferate after brain injury. I believe turning glial cells that are the neighbors of dead neurons into new neurons is the best way to restore lost neuronal functions.”
Chen’s team previously published research describing a sequence of nine small molecules that could directly convert human glial cells into neurons, but the large number of molecules and the specific sequence required for reprogramming the glial cells complicated the transition to a clinical treatment. In the current study, the team tested various numbers and combinations of molecules to identify a streamlined approach to the reprogramming of astrocytes, a type of glial cells, into neurons.
“We identified the most efficient chemical formula among the hundreds of drug combinations that we tested,” said Jiu-Chao Yin, a graduate student in biology at Pen State who identified the ideal combination of small molecules. “By using four molecules that modulate four critical signaling pathways in human astrocytes, we can efficiently turn human astrocytes—as many as 70 percent—into functional neurons.”
The resulting chemically converted neurons can survive more than seven months in a culture dish in the lab. They form robust neural networks and send chemical and electrical signals to each other, as normal neurons do inside the brain.
Using three of the small molecules instead of four also results in the conversion of astrocytes into neurons, but the conversion rate drops by about 20 percent. The team also tried using only one of the molecules, but this approach did not induce conversion.
Chen and his team had previously developed a gene therapy technology to convert astrocytes into functional neurons, but due to the excessive cost of gene therapy—which can cost a patient half a million dollars or more—the team has been pursuing more economical approaches to convert glial cells into neurons. The delivery system for gene therapies is also more complex, requiring the injection of viral particles into the human body, whereas the small molecules in the new method can be chemically synthesized and packaged into a pill.
“The most significant advantage of the new approach is that a pill containing small molecules could be distributed widely in the world, even reaching rural areas without advanced hospital systems,” said Chen. “My ultimate dream is to develop a simple drug delivery system, like a pill, that can help stroke and Alzheimer’s patients around the world to regenerate new neurons and restore their lost learning and memory capabilities.”
The researchers acknowledge that many technical issues still need to be resolved before a drug using small molecules could be created, including the specifics of drug packaging and delivery. They also plan to investigate potential side effects of this approach in future studies in order to develop the safest drug pills. Nonetheless, the research team is confident that this combination of molecules has promising implications for future drug therapies to treat individuals with neurological disorders.
“Our years of effort in discovering this simplified drug formula take us one step closer to reaching our dream,” said Chen.
The Latest on: Small molecules
via Google News
The Latest on: Small molecules
- Sugar alters compounds that impact brain health in fruit flieson September 6, 2019 at 2:38 pm
When our bodies metabolize food, that food is broken down into metabolites -- small molecules that perform many functions in the body, including providing fuel to cells and activating or inhibiting ...
- Insilico Medicine Brings GENTRL AI System to Open Source for Drug Discoveryon September 6, 2019 at 8:20 am
The traditional drug discovery starts with the testing of thousands of small molecules in order to get to just a few lead-like molecules and only about one in ten of these molecules pass clinical ...
- Researchers develop new DNA microscopy techniqueon September 6, 2019 at 6:39 am
The process involves researchers mixing up cell or tissue samples with sequences of single-stranded DNA, selected to attach to the specific molecules to be studied. For example, if it involves a ...
- Scientists develop a deep learning method to solve a fundamental problem in statistical physicson September 6, 2019 at 5:08 am
But this is impossible because the number of possible structures is astronomically large even for small molecules. Therefore, the usual approach is to simulate the dynamical motion and ...
- Resolution of ångström-scale protein conformational changes by analyzing fluorescence anisotropyon September 6, 2019 at 4:54 am
Conformational changes within typical protein molecules are rapid and small, making their quantitative resolution challenging. These changes generally involve rotational motions and may thus be ...
- New method for imaging biological moleculeson September 6, 2019 at 4:44 am
selected to attach to the specific molecules that are going to be studied. If it for example involves a specific protein that is going to be investigated, small DNA snippets are used that bind to ...
- Novel Molecules Designed by Artificial Intelligence in 21 Days Are Validated in Miceon September 3, 2019 at 11:24 am
One lead candidate was tested and demonstrated favorable pharmacokinetics in mice. The traditional drug discovery starts with the testing of thousands of small molecules in order to get to just a few ...
- Downstream Processing of Complex Molecules, Pure and Simpleon September 3, 2019 at 4:44 am
The company’s custom resins, which adsorb and permit the subsequent recovery of desired molecules, have been used for many applications ... and it can be used to run about 10 small-scale experiments. ...
- The scientist who makes smart devices from mere moleculeson August 27, 2019 at 11:35 pm
They use sophisticated machines, some custom-made, to work with and observe the behavior of molecules too minuscule to see or manipulate. “A molecule is very, very small. I cannot handle it. I started ...
- Seeking Small Molecule Drugs to Control mRNA Translationon August 27, 2019 at 9:42 am
Well that’s exactly what Anima Biotech is aiming to do. “We are going after mRNA translation to specifically target protein production using small molecules,” Yochi Slonim, co-founder and CEO of Anima ...
via Bing News