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Monday, March 07, 2011

An Old Idea

The company is called NeuroPhage. The idea is one that I have personally worked on at several different companies. Bind something to amyloid beta (antibody, phage, peptide) and amyloid plaques will not form. The population of potential customers and their end of life spiral makes this disease indication enormously popular among biotechnology companies. You might call this one the holy grail of biotech.

The concept makes several assumptions. It is assumed that binding to amyloid beta in the laboratory will scale to binding amyloid beta inside the human brain. Scaling from a cell line in a petri dish, to an animal model, to a human being, is not something that bio-scientists can rely on.

It is assumed that preventing the formation of amyloid plaques will result a significant reduction in the symptoms of Alzheimers Disease.

It is assumed that phage will be more efficacious than using antibodies or small molecule approaches.

Having done this research I take great interest in the amyloid beta story. I watched others attempt to cure or treat this disease in Cargo Cult amazement. At the highest levels the amount of thought that seemed to go into the "research" was to hire people to find the binder. The executive view (and their investors) was to name the molecule and send in the lower ranking people to finish up the details... of curing Alzheimer's!

On NeuroPhages' website they offer up some evidence. They begin with the perfect world graphic arts version of the disease and how the drug will work. They then show two pictures. In one you see the plaques in a "vehicle control", which appears to be a brain slice. In the other picture there appears to be far less plaques. That is the drug working.

This is a red flag. Science is not done by selective photography. I've seen this trick used in many fields, especially RNAi. You show a knock-down by simply finding the highs and lows of a non-homogeneous system. In this case the system is a brain slice. As far as we know the pictures offered up could be from the same brain slice. We are left to trust the authors that they are not interested in pulling the wool over our eyes.

We're off to a bad start. Now comes the worst part. How do they propose the drug get into a humans brain? How do you measure phage floating around in a brain, breaking up plaques. The Alzheimer's patient is not officially diagnosed with the disease until after an autopsy. Where is the graphic art depiction of drug administration and finding of the target? There is an entire field of science that is not being addressed by the Cargo Cult here. It's called ADME. Tracking the phage on its journey into the body, to the plaques, breaking up the plaques and being cleared is not something that can be done. That frees up management to worry about other things like financing and perhaps adding information to one of the sparsest websites in the biz.

It won't work. I've seen it not work over and over. It's an idea that is taken to the point of, "what do we do next?" and left off to lower paid worker bees. In real science, this is the starting point. Did this really work? How did it work? Does it work every time? Will it work in a human being? The questions are instead left up to the white lab coat people who have only one option in reporting their findings, tell management it works and don't bother with the details that weren't ask for. Keep the story just as it is on the website. There is no turning back now. Look to the skies and wait for the delivery of the Cargo Airplane that carries the cure for Alzheimer's. Once it lands get your sales people together and get ready to make some money.

1 comment:

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