The World Economic Forum (WEF) has asked a group of international technology experts to identify this year's top 10 emerging technologies. After collecting nominations from other experts around the world, the group evaluated dozens of proposals according to a set of criteria. Do the technologies proposed have potential benefits for societies and economies? Can you change the established procedures? Will they be expected to make significant progress in the next few years? "The emerging technologies today will shape the world soon and far into the future tomorrow – impacting the economy and society as a whole," said Mariette DiChristina, editor-in-chief of Scientific American and chair of the Emerging Technologies Board of Directors. Looking for sources of innovation, IO will showcase the top 10 emerging WEF technologies in a 10-part series. Today: Unordered proteins as medicine
After the release of Part 10, you will find the entire series here.
Scientists have identified a particular class of proteins that cause diseases such as cancer or neurodegenerative diseases. These "inherently disordered proteins" (IDPs) looked different from proteins with more stable structures that were better known in cells. IDPs are designers that become visible in the interaction of individual components that are constantly changing in configuration. This loose structure allows IDPs to gather different molecules of critical moments, such as during a cell's response to stress. Less flexible proteins usually have a limited number of binding partners. Failure to work properly by these displaced persons can lead to illness.
It cannot be treated
Medical researchers have not been able to develop treatments to remove or regulate defective IDPs. Many have even called it "incurable," according to WEF researchers. Because most drugs currently used need stable structures to detect them, and IDPs do not remain stable enough. Known messy proteins that can promote cancer – including c-myc, p53 and K-RAS – have proven elusive. However, that picture is starting to change, according to WEF researchers.
Scientists use radical combinations of biophysics, computational power and a better understanding of how IDPs work to identify compounds that can inhibit these proteins. Some have proven to be promising drug candidates. In 2017, researchers in France and Spain demonstrated that it is possible to target and actually address the variable “blurred” interface of IDPs. They showed that a drug approved by the Food and Drug Administration called trifluoperazine (used to treat psychotic disorders and anxiety) inhibits NUPR1, a messy protein involved in some form of pancreatic cancer. Extensive screening tests to screen thousands of drug candidates for their therapeutic potential are beginning to yield results. Other molecules have been identified that act on internally displaced sites, e.g., beta-amyloid involved in diseases such as Alzheimer's disease.
This list will continue to grow, especially as the role of IRLs in key cellular components, the so-called membrane-free organelles, becomes increasingly clear. These organelles, often referred to as droplets or condensates, are vital cell molecules – such as proteins and RNA – occasionally approach each other, but separate each other. Proximity allows certain reactions to take place more easily; separation prevents different reactions. Scientists have developed powerful new tools for molecular manipulation, such as Corelets and CasDrop, that allow researchers to control how these droplets form. Using these and other tools, researchers have found that IDPs can help control the assembly, operation and disassembly of droplets.
This finding is important because IDPs interact with different partners during droplet formation, sometimes even for a few moments taking on new forms. It may be easier to find drugs that in other forms can affect IDPs. Researchers around the world are working to uncover this fall-related mechanics.
Treatment of incurable diseases
The industry also relies on the therapeutic potential of IDPs. Biotechnology company IDP Pharma is developing a type of protein inhibitor for the treatment of multiple myeloma and small cell lung cancer. Graffinity Pharmaceuticals, now part of NovAliX, has identified small molecules in the fight against unmodified tau protein, which is involved in Alzheimer's disease. Cantabio Pharmaceuticals is looking for small molecules to stabilize IDPs involved in neurodegeneration. And a new company, Dewpoint Therapeutics, is exploring the idea that droplets and their messy components can serve as targets for drugs by joining molecules for enhanced reactions. It is increasingly likely that these once "uncommon" proteins will cross pharmaceutical development over the next three to five years.
(Most of this article is from a report on the Top 10 New Technologies in 2019).