An article that went up on Science Daily today:
http://www.scienceda...00419172842.htm
Some highlights:
Stanford University School of Medicine researchers have identified several small molecules that mimic a key but cumbersome protein in the brain, a discovery that could open the door to new therapies for a variety of brain disorders. The protein, designated by the acronym BDNF, is known to be involved in important brain functions that include memory and learning.
BDNF belongs to a family of proteins called nerve growth factors, which are critical during development of the nervous system. When a growth factor binds to its receptor on the surface of a neuron, or nerve cell, it can trigger a cascade of signals inside the cell that direct the cell to survive, grow a projection extending to nearby or distant cells, or form a specialized connection with another cell that lets those two cells communicate. And in a few areas of the brain where new nerve cells can be formed, BDNF promotes this process. But its activity is diminished in certain neurodegenerative disorders, such as Huntington's disease. Even in healthy individuals, its levels decline gradually with age.
Using BDNF itself as a therapeutic drug would be tough, Longo said, as protein drugs are not only costly to make but can't be taken orally (our digestive tracts make no distinctions between proteins in pills and proteins in Porterhouse steaks) and so would have to be injected. Even then, BDNF is very rapidly broken down in the body. "It lasts for only about a minute in the blood," said Longo, who also holds the George and Lucy Becker Professorship. Finally, the blood-brain barrier, which has evolved to protect the brain from undesirable foreign substances, would effectively bar entry to blood-borne BDNF. "So for neurologic disease, it won't reach its target."
Of the million molecules tested, about 2,000 gave signs of having possible BDNF-like TrkB-binding activity. To narrow this list, the investigators used a number of rules of thumb about what kind of molecule makes a drug likely to be nontoxic, more easily absorbed and so forth. "We ended up with 14 that looked pretty good," said Longo.
Of the seven tested molecules, five had the BDNF-like ability to prevent neurons cultured in a dish from dying. The four most active are discussed in the new paper.
The patents for these four compounds are held by the University of North Carolina and UCSF, where Longo worked before coming to Stanford. While at UNC, Longo founded PharmatrophiX, a company focused on the commercial development of small molecules similar to and including those identified in this study.
I'm going to see if I can get my hands on this paper.
Edit: Used incorrect tags.
Edited by babcock, 21 April 2010 - 12:04 PM.
