- by I enjoyed this feature at Nature Medicine on the clinical trials that people are looking forward to seeing the readouts from in 2025. It includes several efforts that I hadn't been paying attention to at all, so it was definitely worth a look. In that latter category are things like ION-717, an antisense therapy that is attempting to lower the levels of prion protein expression in diseases like Creutzfeld-Jacob. The first results are going to be mostly pharmacokinetics and safety, […]
- by Some years ago, I was part of a team looking at various therapeutic options in the sickle cell disease area. At the time, there was a small biotech company called GBT (Global Blood Therapeutics) that had an unusual approach. As most people know, the underlying cause of sickle cell disease is a mutation in the crucial oxygen-carrying hemoglobin protein, one that makes it more likely to aggregate and polymerize. This process is what bends the erythrocyte cells into the shape […]
- by Chimeric antigen-receptor T cell (CAR-T) therapy has been an amazing story overall. People had been trying to turn T cells against various sorts of tumors for a long time, because they're pretty fearsome when they're engaged, but attempts kept coming up short. That was due to lack of knowledge about the (extremely complex) landscape of T-cell activation and function, but that gap finally closed in 2011 with the dramatic recovery of a patient who was weeks from death from leukemia. […]
- by This is a fascinating article from Jeffrey Flier of Harvard about research done in the late 1980s and early 1990s on the now-famous GLP-1 therapies. He was involved in a startup company that had a development deal with Pfizer in this area, and the article is a detailed look at how the company went under as Pfizer dismissed the idea of GLP-1 injectables for diabetes (let alone any ideas about weight loss in a nondiabetic patient population). The team had […]
- by There's been some interesting news on the pharmacological-interventions-in-aging area. This new paper reports a trial of metformin in aging male cynomolgous monkeys (13 to 16 years, roughly 40-50 year old by human standards). A treatment group got 20 mg/kg metformin for over three years (roughly ten years of human lifespan) and these were compared to matched control animals of the same age (and to both much younger and to middle-aged cynos as well). The results seem to have been pretty […]
- by Well, since I was talking about CAR-T therapies here the other day, I wanted to highlight this new paper in Cell. Unlike that other post, though, this one has nothing to do with oncology but rather with the rapidly expanding field of using these modified T cells for severe autoimmune diseases. Earlier reports showed remarkable results in patients with refractory lupus, and that same team published follow-up studies earlier this year in these patients along with others who suffered from […]
- by I wish that I shared Alex Tabarrok's optimism here. He says that "AIs with access to vast databases of genes, proteins, networks and so forth will enable new simulations and learning as has already happened with protein folding", and I can see where that might be an attractive prospect. But there are some major problems with it, in my view. I've made some of these arguments sporadically in other places, but I'll try to put them all together here, with […]
- by Here's a new paper with interesting data on the hits that come out of large computational docking efforts, and in particular, the hits that aren't actually hits. The authors (the Shoichet group from UCSF) have a lot of experience in this sort of work, and they – like others in the field – have noticed that there's more than one type of wrong answer that turns up in virtual screening in addition to the hits that turn out to be […]
- by I've been meaning to write about this case – you see this sort of thing once in a while, but overall it's rare that it gets to the point of filing civil action paperwork. AbbVie is accusing the Chinese company Beigene of stealing their intellectual property for a BTK protein degrader molecule. And the lawsuit says that former AbbVie scientist Huaqing Liu was working on their BTK degrader program until his retirement (the lawsuit puts that in quotation marks!) in […]
- by I enjoyed this recent paper here in Science, because (like many organic chemists) I've always enjoyed cycloaddition reactions. I honestly don't know when the last time I ran a straight-up Diels-Alder reaction was, though. That's the prototype 4+2 cycloaddition to form six-membered rings, but it doesn't come up very often in the synthesis of drug compounds. 3+2 dipolar ones to form five-membered heterocycles, now that's another matter, but I think that one reason we don't see so many classic Diels-Alders […]
- by Here's a lesson that's not very fun to learn: in drug discovery, you can go after ambitious targets, be a pioneer, make your clinical trial endpoints, get FDA approval, launch products that treat patients who have never been treated before. . .and still fail. That looks very much like what's happening to Bluebird Bio, one of the big forces in modern gene therapy research. Back in 2019 and early 2020, their stock was between $40 and $50 a share, and […]
- by Charles Piller and the team here at Science dropped a big story yesterday morning, and if you haven't read it yet, you should. It's about Eliezer Masliah, who since 2016 has been the head of the Division of Neuroscience in the National Institute on Aging (NIA), and whose scientific publication record over at least the past 25 years shows multiple, widespread, blatant instances of fraud. There it is in about as few words as possible. As is so often the […]
- by The BIOSECURE Act (which I last wrote about here) seems to have just passed a House of Representatives vote yesterday, even after a brief news flurry about one or more members who had decided to vote against it. The vote was 306 to 81, which is pretty decisive, especially under current conditions in the House (although to be sure, almost all the No votes were from Democrats). (Update: I see from Steve Usdin's article in BioCentury that two of those […]
- by The FDA recently approved a new drug for schizophrenia treatment, but that statement needs a few qualifiers. The pill is actually a mixture of two drugs (we'll get to that in a minute) and the main ingredient is not exactly new, having been discovered over thirty years ago. And we'll get to that right now, after a bit on schizophrenia itself. This is a hard, hard disease to treat. And that's not least because it's not a very well-defined one. […]
- by Just about a year ago, I wrote here about Cassava Biosciences. It's a pretty tangled story, and I won't try to recapitulate it all in this post. But it's about their drug candidate simufilam, and whether it's a viable Alzheimer's therapy or not. The problem is that the research behind the drug, and the idea of targeting a brain protein called filamin in general, is based on a series of papers from a group at CUNY and other associated researchers […]
- by Y'know, the topic of fraudulent research has been coming up a lot here recently, so I wanted to bring up one more aspect of the problem while it's on my mind. So many of these cases have turned on faked graphical representations of data – Western blots that have been cut-'n-pasted to say just what you want them to say without any of that inconvenient Other Stuff, photomicrographs of cells and tissue slices that illustrate Great Things Happening where they […]
- by This is a nice overview in Cell on vaccine history and new areas that are being explored. For sheer public health benefit, once you establish a clean water supply it's very hard to beat effective vaccines. We have wiped out smallpox as a disease, one that had been dreaded all the way back to prehistory. We are tantilizingly close to doing the same with polio. Other diseases that used to be a common feature of life (especially for children) are […]
- by The 2024 Nobel Prize in Medicine/Physiology has gone to Victor Ambros (of the UMass Medical School) and Gary Ruvkun (of Harvard) for the discovery of micro-RNAs. This is a solid award indeed, and highlights the way that RNA has been sort of taking over the world in recent decades. As I've mentioned here before, back in the ancient days when I was first learning biology, we all knew about messenger RNA, transfer RNA, and ribosomal RNA (although we didn't think […]
- by I think that this paper represents a first, although the overall technique calls back to an earlier era. Back In The Day, meaning "before molecular biology", microscopy (optical and electron) was one of the primary ways that you identified a particular infectious organism (bacterial in the former case, viral in the latter). But here's a modern example. It comes from the farmed mealworm industry (in this case, the closely related "superworm", larval stage of the beetle Zophobas morio. These are […]
- by The 2024 Nobel Prize in Chemistry has gone to David Baker (of the University of Washington) and to Demis Hassabis and John M. Jumper of Google/DeepMind for computational prediction of protein structures. This is one of those awards that is not really a surprise – as the abilities of these methods have become clear, the phrase "protein folding problem" has begun to disappear from the language as a reference to some huge, intractable feat. As always, I can recommend the […]
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