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Biotech / Medical : AMLN (DIABETES DRUGS) -- Ignore unavailable to you. Want to Upgrade?

To: D.Right who wrote (932)	11/9/1997 12:29:00 AM
From: Henry Niman	Respond to of 2173

Type II diabetics develop insulin resistance which is overcome by activating two hormone receptors, PPAR gamma and RXR alpha. The insulin resistance is due to a deficiency in the genes controled by these two hormone receptors, both of which are activated by natural hormones. Rezulin and Targretin restore this difficiency. They are not "add ons", whatever that means.

To: D.Right who wrote (932)	11/9/1997 12:34:00 AM
From: Henry Niman	Respond to of 2173

Here's on of my posts from the LGND thread about an article in the Financial Times: More recently (Aug 14, 1997) FT came out with another large article by the same author called "Hormonal make-over" with a subtitle "...on the emergence of an important new class of drug." It begins: "Hormones are often blamed for everything from bad behavior among adolescents to bad marriages. Yet the public image of these substances, which are released in the body to regulate different funstions, may soon receive a makeover. Researchers believe hormones might soon emergr as an important new drug class for treating a wide range of illnesses, from obesity to cancer. The first example of this new generation of drugs are poised to be launched over the next few years. Ligand, a small pharmaceutical group, is pinning its hopes for a new way to control diabetes on a synthetic hormone called Targretin, which has just entered clinical trials. The company is also working on hormonal treatment for various cancers and heart disease. Eli Lilly, the pharmaceutical group, hopes to have a drug for osteoporosis, the bone disease, on the market soon. The drug, Raloxifene, is based on Lilly's synthetic version of the hormone, oestrogen, and is in Phase III clinical trails, the last step before submission for approval to the US Food and Drug Administration. The company is also studying oestrogen's impact on Alzheimer's disease. Most scientists believe hormones represent an enormous and relatively untapped source of pharmaceuticals. 'There are probably dozens, if not hundreds of hormones out there that have not even been discovered yet,' says David Mangelsdorf, a researcher at the Howard Hughes Medical Center in Texas. The article goes on to describe hormones in general as well as a search for more specificity (as with SERMs). Another large section related to Ligand is: "Hormones seem to have the largest impact on age-related diseases - heart disease, cancer, diabetes, obesity, Alzheimer's, and osteoporosis are all illnesses that disproportionately affect the elderly. The significance of this relationship is still unclear, but scientists are putting together some theories. 'People seem to be born with a pre-set ability to produce a certain number of hormones,' says Ron Evans, chairman of the California based Salk Institute and a leading hormone expert. 'As we age, we make fewer hormones.' Fewer hormones in turn means lower numbers of certain enzymes, whose absence makes it easy for disease to take hold. Ligand, for instance, believes that retinoidal hormones are responsible for the production of insulin. As the number of retinoids in the body decreases, diabetes occurs. By replacing retinoidal hormones in the body, Ligand theorizes, Targretin can constitute a prevention device. While it is tempting to see hormones as a potential pharmaceitical fountain of youth, scientists caution that very little is known about their precise impact on the body. 'While aging is probably hormone related, it's unlikely that people will be able to pop a pill that cures all of the ill effects of getting older,' says Mangelsdorf. 'But we may be able to selectively target age related diseases.' The belief that there are large numbers of undiscovered hormones, as well as the wide variety of responses each hormone elicits, has created hope that hormones can be used for intervention in many ailments. Synthetic hormone drugs would be patentable, available in oral form, and likely to be taken for a lifetime."

To: D.Right who wrote (932)	11/9/1997 12:29:00 PM
From: Henry Niman	Read Replies (2) \| Respond to of 2173

I think there is a fundamental misunderstanding of non-polypetide hormones in general and Rezulin in particular, so it might be useful to review a few basic concepts on hormones and analogs. Polypeptide hormones are the target of Biotechs. These gene products are injected, find an appropiate receptor on the surface of the cell and cause the receptor to change shape which then transmits the signal inside the cell and eventually affects which genes are expressed in the cell. Non-polypeptide hormones are much smaller, so the can be cheaply synthesized in the lab, they are taken orally, and they diffuse into cells and find appropriate receptors which then change shape and eventually affect which genes are expressed in the cell. Analogs of these hormones can have two general effects. If the analog mimics the hormone, then it is an agonist. If it blocks the hormone, then it is an antagonist. The classification is somewhat of an oversimplification, because the same drug can act as an agonist in one cell type, but an antagonist in another (because the ultimate controllers of gene expression are complexes made of different combinations in different cell types). Drugs that are agonists can be referrred to as "hormone replacements" because they mimic the hormone. Many, if not most hormone analogs, are agonists. Pramlintide is an agonist of the polypeptide hormone amylin. Rezulin is an agonist of non-polypeptide hormone prostaglandin J12?. Targretin is an agonist of the non-polypeptide hormone 9-cis-retinoic acid. Each analog mimics a natural hormone. An "add on" drug is a term that is an agonist for a misconception.