Category: Drug Development

Small Molecules that Plays an Antibody on TV

So, Warp Drive was just acquired by Revolution Medicines. It was unfortunately not an acquisition based on strength, but both of the companies are Third Rock companies, and I have high regard for Third Rock, so hopefully the Warp Technology will survive. Warp was also co-founded by George Church, who trained me, Continue reading “Small Molecules that Plays an Antibody on TV”

Beyond Drugs

Other than surgery, drugs are mainstays of disease therapy. We take chemicals to treat ourselves, but why is that? Why chemical, as opposed to light, ultrasound, electricity, odors, or some other type of intervention? The reason is that plants, from which most of our drugs come, have spent millions of years engaged in medicinal chemistry, and have created some of the most potent biological molecules.

But there are exceptions. For example, one group at Harvard recently published that exposing mice to flashing lights cleared beta amyloid plaque in the brain. This was likely because the flashing light drove gamma oscillations in the brain. Continue reading “Beyond Drugs”

Someone Who Really Understands Drug Development

Today, I ran across someone on LinkedIn who has the best grasp of declining R&D productivity from a macro level that I’ve ever seen. Kelvin Scott has a series of very insightful articles such as the ones below and a fantastic presentation.

I highly recommend you take a look though he’s more pessimistic than is warranted (he thinks that the industry is doomed). Many of his observations are on the mark, in that things cannot continue on the same trajectory. In my view, that means that they won’t–I think there will be structural changes in pharmaceutical R&D that will reverse the trends, because no one is going to be able to run companies forever with a negative return on investment.

For example, he discusses how there are too many companies chasing the same target that drives ROI down for everyone. That is probably true, and of course that means that eventually some of the companies will go out of business. When that happens, returns will rebound.

Continue reading “Someone Who Really Understands Drug Development”

RNA as a Target? Heck Yeah.

There was recent article in Nature Reviews Drug Discovery entitled “Small molecules against RNA targets attract big backers.” The article described several molecules that came out phenotypic screeening programs at Novartis, Merck, and Pfizer. These molecules target RNA instead of protein. “This was a huge surprise to us,” says RAjeev Sivasankaranm head of neurosciences group at Novartis. The group had been trying for years to figure out how a small molecule LMI070 works.

It should have been no surprise. RNA is turning out to be far more important than protein in cellular biology. I suspect that many of the molecules we currently think work through proteins will turn out to actually work through RNA. And many of the molecules where we have been unable to explain the mechanism of action (and there are many, including gold), will turn out to work via RNA.

Since we used to think protein was the most important class of target for drugs, we forced most of the molecules into that paradigm. Now that it’s becoming clear that this is not the case, our understanding of the drugs’ mechanism of action are being transformed.

To Sleep, Perchance to Dream… Or Not

You know those people who only need 4 hours of sleep a night, yet who are energetic to the point of making you feel exhausted just by seeing what they do in a day? Well, there’s an app for that. OK, not really, but there is a gene for that. It’s called DEC2 (also called BHLHE41), and the evidence for it is pretty convincing. The group that originally identified this gene even made mice with a mutation in the gene and the mice also became short sleepers, and at least one other group has identified mutations subsequently in the same gene in other families with short sleep phenomenon.

What does this gene do, can I have a copy of that mutation, you are asking yourself. Continue reading “To Sleep, Perchance to Dream… Or Not”

Colon Cancer and Bacteria

The bacteria called Fusobacterium nucleatum plays an important role in causing gingivitis and periodontal disease. It is also found in the placenta. Gingivitis is an interesting disease, because people who have gingivitis also tend to have higher risk of a number of other problems, such as diabetes and heart disease. It has been a long-running debate whether gingivitis causes these other diseases or whether it’s just a non-causal correlation.

Into that debate drops this bombshell: a paper recently published in Nature just reported that Fusobacterium, which was previously reported to be found in many patients with colon cancer and to induce tumors (in this paper, they show the bacteria recruit immune cells to the tumor, which is very very bad Continue reading “Colon Cancer and Bacteria”

Being Sleepy and Tired

There is a fantastic post by luysii on his Chemiotics II blog. In it, he discusses his theory that senescent cell may be producing mediators that cause chronic fatigue syndrome (CFS). I think it’s a fascinating idea.

CFS is a terrible disease, made worse by the fact that some physicians don’t believe that it exists. Trust me, it does.

An interesting things about the disease is that it tend to occur in high income countries, and almost never in developing countries, and that in my experience, it tends to occur in women from mid to higher socioeconomic strata. This is in contrast to fibromyalgia, which Continue reading “Being Sleepy and Tired”

Will We Cure Diabetes, Heart Disease, and Alzheimer’s Disease One Day?

FDA, in 2008, did something that many people thought was preposterous. They began requiring companies to prove that diabetes drugs they developed did not kill people. Actually, to be more specific, they required the companies to prove that the risk of dying on the drug was not more than 1.8X higher than not being on the drug.

This caused an uproar. To prove such a ridiculous thing, some companies howled, would Continue reading “Will We Cure Diabetes, Heart Disease, and Alzheimer’s Disease One Day?”

Rosacea and Tiny Mites

Mites scare me.

When I was an undergrad, working on fruit flies (I would sit in a coldroom, which was essentially a big refrigerator, injecting fruit fly eggs with a tiny glass needle I blew myself, making some of the very early transgenic fruit flies), mite infestations would occasionally sweep through the lab, killing hundreds of thousands of fruit flies. Some of the flies represented years of work by students and postdocs.

Which brings us to rosacea. Continue reading “Rosacea and Tiny Mites”

It’s a Shame that Scientists Develop Drugs, Instead of Engineers

Museum of Natural History. That’s a funny name, isn’t it? The whole building is full of scientific and biological items like skeletons and fossils. Where’s the history part?  Shouldn’t it be called Museum of Science? Most people would put science and history on the opposite end of the spectrum.

When you hear a name like that, it almost feels like someone’s trying to obfuscate, trying to Continue reading “It’s a Shame that Scientists Develop Drugs, Instead of Engineers”