The World Economic Forum (WEF) has asked a group of international technology experts to identify the top 10 emerging technologies this year. After gathering nominations from other experts from around the world, the group evaluated dozens of proposals against a set of criteria. Do the proposed technologies have the potential to bring great benefits to societies and economies? Could you change the established procedures? Are there any expectations that they will make significant progress over the next few years? "Emerging technologies today will shape the world soon and tomorrow in the future, thus affecting the economy and society as a whole," said Mariette DiChristina, Scientific American's editor-in-chief and president. Emerging Technologies Steering Committee. In search of the origins of innovation, IO will present the top 10 emerging WEF technologies in a series of 10 articles. Today: disordered proteins as a medicine
After the publication of Part 10, you will find the complete series here.
Scientists have identified a specific class of proteins responsible for diseases such as cancer or neurodegenerative diseases. These "inherently disordered proteins" (IDPs) were different from more stable and well-known proteins in cells. PDIs are form changes that become visible in the interaction of individual components, which constantly change in configuration. This loosely structured structure allows displaced people to group together various molecules of critical moments, for example. during the reaction of a cell to stress. The less flexible proteins usually have a smaller number of binding partners. If these displaced people do not function properly, an illness can occur.
Medical researchers have not been able to develop treatments to eliminate or regulate defective PDIs. Many have even been described as "untreatable," according to WEF researchers. Because most drugs currently used need stable structures to detect them, and IDPs do not remain stable for long enough. Known disordered proteins that can promote cancer – including c-myc, p53 and K-RAS – have proven elusive. However, this picture is beginning to change, according to WEF researchers.
Scientists are using radical combinations of biophysics, computational power, and better understanding how PDIs work to identify compounds that can inhibit these proteins. Some have proven to be promising drug candidates. In 2017, researchers in France and Spain showed that it was possible to actually target and address the variable "fuzzy interface" of a PDI. They have shown that a drug approved by the Food and Drug Administration called trifluoperazine (used to treat psychotic disorders and anxiety) inhibits NUPR1, a disordered protein involved in some forms of pancreatic cancer. Large-scale screening tests to evaluate the therapeutic potential of thousands of drug candidates are beginning to bear fruit. Other molecules acting on IDPs have been identified, for example: beta-amyloid involved in diseases such as Alzheimer's disease.
This list will continue to grow, especially as the role of displaced people in key cell components, called membrane-free organelles, is becoming clearer. These organelles, often called drops or condensates, sometimes bring together vital cell molecules, such as proteins and RNA, but separate the others. Proximity allows some reactions to occur more easily; the separation prevents different reactions. Scientists have developed powerful new tools for molecular manipulation, such as Corelets and CasDrop, which allow researchers to control the formation of these droplets. Through these tools and others, researchers have discovered that IDPs can help control the assembly, operation and disassembly of droplets.
This discovery is important because PDIs interact with different partners during the formation of droplets, sometimes even taking new forms for a few moments. It may be easier to find drugs that could affect IDPs in their other forms. Researchers all over the world are trying to discover this mechanism linked to drops.
Treatment of incurable diseases
The industry also supports the therapeutic potential of displaced people. The biotechnology company IDP Pharma is developing a type of protein inhibitor for the treatment of multiple myeloma and small cell lung cancer. Graffinity Pharmaceuticals, which is now part of NovAliX, has identified small molecules to fight against unmodified tau protein, implicated 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 disordered components can serve as targets for drugs by bringing together molecules for improved reactions. It is increasingly likely that these proteins, which were once "unusual", will be in the crosshairs of pharmaceutical development over the next three to five years.
(Most of this article comes from the report on the top 10 emerging technologies published in 2019).