Cephalon Inc. is finding that its small organic molecule-compounds can promote the survival of diseased or damagedneurons in vitro.
Michael Lewis, senior director of scientific affairs at the WestChester, Pa., neurotech company (NASDAQ:CEPH), described thepreclinical data on the compound, K252a, and its analogs onMonday at the 22nd Annual Meeting of the Society forNeuroscience in Anaheim, Calif.
Lewis explained that K252a acts as a partial agonist of high-affinity nerve growth factor (NGF) receptors. K252a hadalready been shown to inhibit various NGF-stimulatedresponses in cultured PC-12 cells -- a line derived from ratpheochromacytoma, a tumor of the adrenal chromaffin cells.
The Cephalon researchers found that K252a can apparently actboth as an agonist -- enhancing the ability of NGF to stimulatecells to make a particular enzyme -- or as an antagonist --inhibiting the process.
Normally, nerve growth factor and other endogenousneurotrophins interact with specific tyrosine kinase receptorsto promote neuronal survival and even regeneration. Butbecause such large molecules can't pass the blood-brainbarrier, they can only be used to treat neurodegenerativediseases or spinal cord injuries if they are delivered directly tothe brain via surgically implanted tubes.
The advantage of K252a is that it can cross the blood-brainbarrier. Therefore it may be able to exert direct neurotrophiceffects -- perhaps stimulating the production of nerve growthfactors inside the brain -- to promote the survival of"compromised" neurons, such as those associated withneurodegenerative diseases or head and spinal injury.
Cellular Implants to Treat Parkinson's
Researchers at CytoTherapeutics Inc. (NASDAQ:CTII) ofProvidence, R.I., are developing cellular implants as treatmenttherapies for Parkinson's disease. Dwaine Emerich and hiscolleagues reported Monday at the neuroscience meeting thatdopamine-producing implants in the brains of elderly ratssignificantly improved the rats' motor skills compared to thecontrols.
The implants consist of encapsulated cultured PC-12 cells thatproduce dopamine. Above all, this neurodegenerative disease ischaracterized by the death of the brain cells that make theneurotransmitter dopamine. Drugs such as L-dopa that treatmany of the disease's symptoms, such as tremor, dementia anddepression, work only in the early stages of the disease. Elderlyrats apparently exhibit disturbances in balance andcoordinated movement together with less locomotion -- someof the same symptoms associated with Parkinson's.
The encapsulated cells in their thermoplastic membrane areextremely biocompatible, Emerich told BioWorld. There are noobvious toxic side effects in either rats or primates. "Inprimates, we have data out to five to six months," Emerich said.
Importantly, unencapsulated cells do not survive in the host,thus averting possible side effects.
"One really attractive feature of this technology is that thedevice is retrievable," Emerich said. If it needs to be replaced,it can be, unlike implants of fetal tissue, for instance.
"We are envisioning treating the symptoms of Parkinson's, notthe disease," Emerich said.
-- Jennifer Van Brunt Senior Editor
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