Andy, The Alzheimer's incidence is lower in men and its because androgen is coverted to estrogen in the brain. I think that the trick is to get the estrogen (or SERM) level higher in the brains of men and women. I have mentioned in the past that LGND didn't really have a neuro program. However, I was talking more about using STATs to mimic growth factors. Of course Robinson has promised a leptin signaling deal by the end of the year and that will involve STATs and the brain.
The Alzheimer's application really comes from the estrogen studies.
Here's a brief background on libraries and screening. Big Pharmas love the non-polypeptide hormones because they are taken orally, can be made cheaply, and can be modified cheaply. Consequently, the make vast libraries of compounds. Even a smaller pharma like AGN can make over 3000 retinoid analogs. Bigger boys have literally 10's or 100's of thousands of compounds. However, its much more difficult to screen these compounds to find the most promising ones. That's where LGND's screening comes into play. LGND has panels of receptors that bind the hormones or analogs.
For the AGN alliance, LGND focused on the 6 closely related receptors (3 RARs and 3 RXRs). However, all of these receptors are part of a huge family. They are related to the estrogen and androgen receptors as well as progesterone, glucocoricoid, minerocorticoid, PPAR alpha, beta, and gamma, HNF4, thyroid hormone receptor, and a host or orphan recpeptors. There are over 75 such recpetors and LGND has most of them. Therefore, they can screen libraries agains a host of receptors and they can put the recptors in a variety of tissue types. As LGND learns about which binding profiles are most interesting as well as which modifications are most useful, they can come up with better drugs through targeted drug screening.
Last year H&Q predicted that the LGND would be the first successfull (i.e. profitable) targeted drug screening company. LGND's alliances provide for development of compounds in areas outside of LGNFD's niche. However, LGND can select (and license back) compounds for cancer applications.
By accessing PFE, AHP, and LLY libraries (and I think they also screened the MRK Damstadt library as well as the National Cancer Institute's natural products library), they can pick out the most promising compounds from 100,000's. |
