Dr. Joanna Jankowsky, assistant professor of neuroscience at Baylor College of Medicine, is conducting research toward therapeutic intervention in Alzheimer's disease.
"The drugs currently available for treating Alzheimer's disease provide only a temporary slowing of cognitive decline," Jankowsky said. "Our goal is to find new ways of treating the disease that may not only stop things from getting worse but which ideally will help to reverse damage that's already occurred."
Testing new strategies
Jankowsky and her colleagues use transgenic mice, mice that contain artificially-introduced genetic material in cells, to model the disease and test new strategies for intervention.
"We understand humans and mice are quite different, however, they share enough biology in common that they can provide valuable information about the basic mechanisms of the disease and offer a system in which we test new treatments before they are considered for clinical trials," she said.
Focusing on peptides, plaque
Jankowsky and her colleagues focus on the role Aβ peptides play in Alzheimer's disease. Aβ is the main component of amyloid plaques, which are formed when the peptide collects into fibrous deposits between nerve cells in the brain. The presence of these plaques is an indication of Alzheimer's disease.
Jankowsky studies mice that reproduce Alzheimer's amyloid pathology because they overexpress a form of the Aβ precursor protein associated with rare, inherited cases of the disease.
Turning off peptide production
"We generated mice that form the plaques just like those found in humans with Alzheimer's disease. With that as a basis, we began to study treatment options," Jankowsky said. "Our first approach was to turn off the production of Aβ peptide."
To do this, Jankowsky and her colleagues developed a mouse in which transgenic expression of the amyloid precursor protein could be turned off by feeding the animals tetracycline-derived antibiotics.
"This system allows us to turn off production of Aβ like a switch," Jankowsky said. "By doing this, we found that the progression of the disease was completely stopped. However, plaques that had already formed did not go away. Now that we had arrested the disease, we would have to devise new ways to reverse the damage."
Jankowsky and her collaborators then began testing ways to remove or "mop up" Aβ peptides left behind after Aβ was switched off. They tested whether the addition of an antibody against the peptide would help the brain remove amyloid plaques that remained. Their latest data suggests that a combination approach – stopping the production of Aβ and then mopping up what's left with an anti-Aβ antibody – works better than either therapy alone.
"The mouse models we are using give us a chance to answer specific questions of how to stop and reverse the disease," Jankowsky said. "But they are mice, not men. Results in animal models don't always translate to humans, but they do help us refine what targets to shoot for in clinical trials."
Maintaining cognitive level
Jankowsky believes the most likely next step in patient care will be to create longer delays before cognitive decline resumes. Her goal, however, is to hold a person at the level of cognitive ability they have at diagnosis, then reverse neuronal damage to restore and preserve maximal function.
"There may be different routes we can take, perhaps by adding layers of treatment that use different approaches, to some day not only arrest the decline but to provide a cure for the disease ," Jankowsky said.