By Randall Osborne
After three years of assaying compounds that might be useful in its pioneering approach to treating Alzheimer's disease, Gliatech Inc. has identified "a couple of different families" of potential drugs — prompting its partner and owner of the compound library, Janssen Pharmaceutica N.V., to extend their collaboration another year.
Terms of the extended deal were not disclosed. Janssen, a Beerse, Belgium-based subsidiary of Johnson & Johnson, of New Brunswick, N.J., also retained the right to renew the pact for yet another year. The collaboration began in 1994. (See BioWorld Today, Oct. 17, 1994, p. 1.)
Kurt Brunden, vice president of research for Cleveland-based Gliatech, said the Janssen decision was based on Gliatech's progress in sifting anti-inflammatory compounds for candidates against Alzheimer's disease, which, he said, Gliatech believes is a sort of "rheumatoid arthritis of the brain."
Postmortem examinations of Alzheimer's patients show concentrations of senile plaques in the brain. The plaques, made of amyloid peptide, have long been suspected as culprits in the disease, but exactly how they might work to cause it has been a mystery. Gliatech's researchers and others have noted that glial cells are strongly activated by plaques, causing the brain to release inflammatory molecules, notably interleukin-1 (IL-1) and tumor necrosis factor, which have been shown in vitro to be neurotoxic.
Clinical Trials Two Years Away
Could Alzheimer's disease be an inflammation of the brain?
"We hypothesize that it is, at least in part," Brunden said. Patients with rheumatoid arthritis, he said, have a very low prevalence of Alzheimer's disease. "The reason appears to be that they are treated with anti-inflammatories throughout their lives," Brunden said.
The challenge is to formulate potent drugs that can be tolerated by the elderly, who often suffer gastrointestinal problems from traditional anti-inflammatories.
"We're trying to identify drugs or compounds that will knock down this glial inflammation but act by different mechanisms than the classic, non-steroidal anti-inflammatories," Brunden said.
That's where Janssen's compound library comes in.
"We've analyzed thousands [of compounds] during these first three years," Brunden said. Narrowing the field to exactly the right one is "essentially brute force," and Gliatech's success in reducing the choices is what caused Janssen to extend their pact, he added.
Gliatech has found a small group of candidates that show promise. "We're not limited to a single compound," Brunden said. "We've got a couple of different families. We're trying to fine-tune the molecule and create the potency, so we can then select a preclinical candidate."
The compounds have been tested using in vitro assays. "Some of the compounds showed activity in vivo as well," Brunden said. But, he concedes, "We don't have any human data at all, to know for sure that the compounds don't have those kinds of [gastric] side effects."
Brunden said Gliatech expects to begin clinical trials in about two years. The idea of using anti-inflammatories against Alzheimer's is "a key idea that's catching on," he added, but Gliatech started early on the research. "There are none that are as far along as we are," he said. *