August 15, 2023
Barry Bunin, PhD Founder & CEO
Collaborative Drug Discovery
"Nanotubes Shred Tumors in Mice." That’s the headline from a Drug Discovery News report on an interdisciplinary team of scientists from the University of Toronto and the Hospital for Sick Children in Toronto which reported an “outside-the-box” treatment for glioblastoma. The article notes that a glioblastoma diagnosis is tantamount to a death sentence, with most patients surviving just over one year with this aggressive brain cancer. Treatment options are limited, and mortality rates have not improved for decades. Their work, described in Science Advances, used what the scientists call “mechanical nanosurgery” to overcome glioblastoma’s drug resistance. They stuffed carbon nanotubes, or CNTs, with magnetic iron nanoparticles. They also labeled the CNTs with an antibody that targets the protein CD44, which is highly expressed in many glioblastoma tumors. To treat the mice, the researchers injected the magnetic CNTs into the brain region that contained drug-resistant glioblastoma tumors derived from human cell lines. The CNTs either entered or adhered to the surface of the cells in that region. The scientists then applied a magnetic field engineered to cause only the CNTs within the tumor region to spin. This disrupted cellular structures both inside and outside cells. “It’s a blunt force,” said Xi Huang a biologist at the University of Toronto and the Hospital for Sick Children, and coauthor of the study. “It’s really causing mayhem in many different places.” That mayhem killed tumor cells and increased the overall survival of treated mice compared with untreated mice.
* * *
Hallucinating New Proteins May Open New Worlds. That’s the basic message that Derek Lowe provides in his recent blog for Science, titled “Protein Design the AI Way.” He points to a report on some of the latest work being done in de novo protein design, and an overview on using a process dubbed “hallucination” that takes a more or less random string of amino acids refined by ML tools into something that should fold into a specific desired three-dimensional structure. The work impressed Lowe, who wrote: “This ability to just come up with new proteins on demand is of course going to permanently alter protein science, to the point that it’s eventually going to be hard to explain to the young ‘uns what it used to be like without it. The possibilities for chemical biology, model systems, and eventually outright therapeutics are so numerous that it’s hard to even know where to start. But to get these to work, we’ll need to know more than a shape we’re trying to mimic: toxicity, immunogenicity, and binding to other proteins that we haven’t even studied are all factors that will have to be explored experimentally. All that knowledge (and what we know about these topics already) will surely get fed back into more advanced versions of protein-design software.”
* * *
FDA Praise for Base Editing, the “Spell-Check for Genes.” A FIERCE Biotech interview with Peter Marks, M.D., Ph.D., and head of the FDA’s Center for Biologics Evaluation and Research, shows a commitment to facilitating faster approvals of gene editing breakthroughs. Marks has voiced his concerns that the agency is simply not approving enough gene therapies, saying earlier this year that it would be a failure if the FDA only approved two to three a year moving forward. To try to ease the backlog, the FDA has so far revamped the Office of Therapeutic Products with more specialized offices and hired more reviewers to match. The article notes Marks is especially interested in base editing, which has been described as “spell- check for genes,” a mechanism by which individual letters on a base pair in the genome can be changed to fix disease-causing mutations. It's one of the latest gene editing features to spawn from the Nobel Prize-winning CRISPR/Cas9 technology. “I think the possibility of genome editing, and particularly the concept of base editors … could be an incredible game changer, not just for rare diseases but more common disease,” Marks said. He couched the comment by saying the agency will need to keep a close eye on off-target effects saying “there’ll be a lot to be learned here.”
* * *
Wall Street Investors Attracted to AI in Drug Discovery and Health Care—Including Small Companies. That’s the basic message from a recent Wall Street Journal article on investor interest in how AI could speed drug discovery. The article reads, in part: “The U.S. spends about $4.3 trillion annually on healthcare, according to data from the Centers for Medicare and Medicaid Services. Some industry executives and investors believe that AI, if used to discover new drugs more efficiently or identify at-risk patients more quickly, could reduce that tab and make new companies at the forefront of the technology more valuable.” The article concludes: “Some on Wall Street think more AI-related gains could be in store. The rally is “something that investors should take pretty seriously on a near-term basis,” said Will Sevush, healthcare equity strategist at Jefferies, because small-cap stocks can post dramatic gains when
investors flock to a popular theme.”
Barry A. Bunin, PhD, is the Founder & CEO of Collaborative Drug Discovery, which provides a modern approach to drug discovery research informatics trusted globally by thousands of leading researchers. CDD Vault® is a hosted biological and chemical database that securely manages your private and external data.