January 02, 2013
Alzheimer's Drug Works In Mice
Mice are lucky they aren't protected by regulatory agencies. If this is a cure in humans will we get it in 7, 8, 9, 10 years?
A new ray of hope has broken through the clouded outcomes associated with Alzheimer's disease. A new research report published in January 2013 print issue of the FASEB Journal by scientists from the National Institutes of Health shows that when a molecule called TFP5 is injected into mice with disease that is the equivalent of human Alzheimer's, symptoms are reversed and memory is restored—without obvious toxic side effects.
If I had Alzheimer's, had access to this drug, and still had enough brain left to understand the above paragraph I'd inject myself with TFP5 immediately. No way would I wait for the drug regulatory process. I might start low and take successively higher doses each day. But I'd certainly not think it made sense to wait for years for clinical trials to be organized. If TFP5 does damage to humans better to run the risk of dying from it in the short term than the slow death of one's mind over several years.
Clinical trials: sure but when? The regulatory apparatus around killer diseases does not let desperate people (who have little to lose after all) to try desperate measures. I'd rather run the risk and if an experimental treatment is going to kill me at least rapidly let the medical researchers know that the treatment is a failure. Go down fighting.
"We hope that clinical trial studies in AD patients should yield an extended and a better quality of life as observed in mice upon TFP5 treatment," said Harish C. Pant, Ph.D., a senior researcher involved in the work from the Laboratory of Neurochemistry at the National Institute of Neurological Disorders at Stroke at the National Institutes of Health in Bethesda, MD. "Therefore, we suggest that TFP5 should be an effective therapeutic compound."
We need faster progress in treating the degenerative diseases of old age like heart disease, Parkinson's, Alzheimer's, and assorted organs failures.
Randall Parker, 2013 January 02 09:11 PM
If I had Alzheimer's, had access to this drug
It's just a peptide, nothing very complex. Hundreds of companies will synthesize and purify custom peptides. It's not cheap but quite straightforward. Problem is, they use a lot of it. 40 mg/kg in mice of a 35 amino acid residue-long peptide (longish). If this translates to humans, 4 grams per day. Very expensive and huge injection volumes (at least 100 ml, probably more).
The mice would already be bankrupt from spending all of their money on medivation/bapineuzumab etc… let alone every drug that’s ever looked good in an animal trial.
Actually I agree with you that the FDA is too conservative (although you may be underestimating some of the early/experimental access options that are already exist) but the far bigger problem is developing drugs is hard.
No word on how long to take it.
I'd go with a permanent IV needle, if that's what it took.
Wonder if this would work if the chemical was dumped into the abdominal cavity? That would help with the volume, ifso.
When Barry Marshall did the work that would ultimately win him the Nobel it was by drinking a petri dish of H. pylori bacterium.
That's how you do it, folks. Too much focus on the minimisation of risk creates illusory benefits and invisible costs. Where possible skip the hurdles and get straight to the results.
"40 mg/kg in mice of a 35 amino acid residue-long peptide (longish). If this translates to humans, 4 grams per day. Very expensive and huge injection volumes (at least 100 ml, probably more)."
Drug dosages usually do not scale with mass, as larger organisms have slower metabolisms. A human with the metabolic rate of a mouse would catch fire, not enough surface area to get ride of the heat. In fact, drug dosages usually scale about with surface area.
So, a mouse, 20 grams, a human, 100,000 grams. 5000 times the mass implies maybe 300 times the dose. 300 * 40 * 0.02 = 240mg. Not 4000mg.
But that is, of course, a very rough approximation indeed, as humans aren't just big mice.
In fact, drug dosages usually scale about with surface area.
Yes, that's the theory always taught but it contradicts reality really badly. For every compound/drug that I bothered to look at LD50 values for mice and humans, they are always of the same order of magnitude per body mass. E.g. (mouse/human) - aspirin: 250/150-350 mg/kg; ethanol: 3.5/5-6 g/kg. And vets *always* scale drugs by dog body weight.
I think that's because LD/50 is often based on acute effects caused by the peak concentration in tissue after a single dose, which is obviously going to scale linearly with mass, it's simple dilution. While therapeutic doses for long term effects are based on clearance rates, which are usually a result of metabolism for anything your kidneys are not going to kick right back out of your body.
"And vets *always* scale drugs by dog body weight."
A linear approximation of an exponential; Dogs don't vary in weight enough to justify doing the math right, nor do people, while humans are 2-6000 times more massive than mice, so no linear approximation is going to be valid. Mind, no simple approximation is valid between species, all you can manage is a first guess.
Went through chemo several years ago, where they're getting close enough to killing you that they have to get the doses precisely right, and they use the surface area rule for some of that, mass proportionate for others, depending on clearance mechanisms.
More problematic is the fact every doctor I've met prescribes the same dose of antibiotics for me, and for my wife, when I'm three times her mass. (Which is probably why she complains antibiotics make her queasy, while I shrug them off.) Don't even bother with mg/kg style doses. I find it more than a little troubling how primitive modern medicine is where the rubber hits the road, they don't even bother applying some of the most basic principles right.
There are a number of neurodegenerative diseases that have effective treatments that are being withheld from people who are in their terminal stages and are suffering the torments of hell.
The failure to sort proponents of social theories into governments that test them not only kills -- it tortures -- particularly when people can't escape monstrosities like the FDA/DEA born of maternalistic social theories.