Month: January 2018

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.

Can You Taste with Your Kidneys? Can You See with Your Blood Vessels?

I’ve only seen scurvy once. I was in training at Barnes Hospital in St. Louis, and a homeless man was admitted with weakness, muscle and bone pain, bleeding gums, and shortness of breath. It turned out that his diet consisted solely of hotdogs (no condiments) and Coke. It’s a good thing he came to tertiary care hospital, because scurvy is so rare now that many physicians wouldn’t even consider it in their diagnosis.

I will admit, though, that I’ve been watching a friend of my son for years, expecting to see my second case of scurvy. This friend only eats white rice. Well, he also eats white bread, and a few other things, but only bland things. I thought he would grow out of it but he still hasn’t, and he’s teenager.

I’ve been puzzled about his dietary habits, but I just read something that might explain this.

In The Medical Detective, Roueché describes a baker who suddenly developed a similar problem. The baker, named Rudy, had a perfectly normal sense of smell and taste until one day, he came down with a cold. Then suddenly, his smell and taste perception changed (and persisted). He couldn’t handle the smell in his pizza bakery any more. The ripe tomatoes smelled rotten. The entire kitchen smelled like burnt plastic. Continue reading “Can You Taste with Your Kidneys? Can You See with Your Blood Vessels?”

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”

Diabetes Drugs for Alzheimer’s Disease?

A recently published paper reported that combination of three diabetes drugs (GLP-1, GIP, and glucagon) improved memory in a mouse model of Alzheimer’s. This is quite remarkable, but not shocking.

There are several competing theories of Alzheimer’s disease. There is the all-but-discredited theory of beta amyloid. I would like to still believe in this theory, having been a proponent of this theory for several years at Elan. It is a compelling theory for several reasons. First, the familial forms of Alzheimer’s disease have mutations that increase beta amyloid. Second, you can cause Alzheimer’s by injecting beta amyloid into the brain. Third, transgenic mouse models targeting beta amyloid can reproduce some of the symptoms of the disease. But unfortunately, data from multiple studies have shown that the theory is incorrect. It is difficult to admit that so much beautiful science (much of it done at Elan) can be so wrong but I think it may be. Continue reading “Diabetes Drugs for Alzheimer’s Disease?”

Gout and Cardiovascular Disease

My best friend was diagnosed with gout recently. I told him to stop ingesting fructose immediately.

Only twenty five years ago, when I was in training, gout looked like it was like a disease on its way to extinction, sort of like tuberculosis. We were taught it used to be common hundreds of years ago but that it was pretty rare. Sure, I had a few patients with gout in my clinic with gout but I would see a case once every couple of months at most.

Now, it’s exploded in frequency.

Gout is very, very bad. Not only because it is excruciatingly painful. (In some patients, you can’t even let a gouty big toe brush against tissue paper without unbearable pain. It’s one of the few things that may rival childbirth in the intensity of pain.) And not only because it is a major risk factor for heart disease. Not only because it causes heart disease. No, it’s very bad because your risk of dying goes up by 25% if you have gout. Continue reading “Gout and Cardiovascular Disease”