An experimental drug combined with an already-popular memory-enhancing compound may further delay memory loss in patients with Alzheimer's disease and other dementias, Johns Hopkins University scientists, in collaboration with researchers from University of North Carolina, have found.
The findings, described in the June issue of Neuropsychopharmacology, also indicate that the experimental treatment in question - a compound known as SGS742 - works by blocking certain chemicals that interfere with memory formation.
"The findings in laboratory animals - both improved memory in our tests and evidence that the drug targets the biology for making memories in the brain - places this drug on solid footing as a candidate therapeutic agent," said the study's lead author, Michela Gallagher.
SGS742, previously shown to improve memory in animals, is an experimental treatment for memory disorders. It is currently in human clinical trials led by California-based Saegis Pharmaceuticals Inc., which holds a worldwide exclusive license granted by the drug's developer.
Gallagher, a Krieger-Eisenhower Professor and the chair of the Department of Psychological and Brain Sciences in the university's Zanvyl Krieger School of Arts and Sciences, said these studies did not address SGS742's potential as a cure or preventive treatment for Alzheimer's disease itself. They were intended, rather, to assess its potential as a treatment for the disease's key symptom: memory loss.
"Memory impairment occurs early in the disease and worsens as the disease progresses. However, until the later stages of the disease, memory is impaired but not entirely gone," Gallagher said. "By augmenting the brain's memory-making ability, drugs could be used to treat this symptom and to improve the quality of life for patients who have a disease that has a slow progression over years."
SGS742 has been found in clinical trials to be beneficial to humans with mild cognitive impairment. The Johns Hopkins team investigated how the compound works. The team compared SGS742 with Aricept ® (generic name: donepezil), an approved and frequently used treatment for Alzheimer's disease manufactured by Eisai Inc. Ltd. The Johns Hopkins researchers found in animal studies that a combination of SGS742 and Aricept ® improved memory to a larger degree than either drug alone, implying a potential for future combination therapy protocols.
The research team conducted this study on 60 normal young male rats who were not memory-impaired. Each rat was given at various times SGS742, Aricept ®, a combination of the two drugs or no drugs at all, and was tested on its skill navigating a series of mazes that placed increasing demands on its memory.
"The mazes were designed to take advantage of the rats' natural foraging instincts," explains Rebecca Haberman, an associate research scientist at Johns Hopkins who is a co-author on the study. "Rats will not readily return to the place where they previously ate all the available food. So we asked the rats to remember where they had found treats in the 'information' session, and to look for food in new places during the recall tests."