It’s an exciting time in Alzheimer’s disease (AD) research, declared a recent CNBC.com article. Enhanced investment in research has led to new and improved treatments for cancer and other common illnesses, with Alzheimer’s perennially lagging in both available treatments and federal funding. But leading researchers, those at Penn among them, are now optimistic that treatments to slow or halt the disease will be available within five years.
Washington has committed some $5.4 billion this fiscal year to cancer research and $3 billion to research on HIV/AIDS, while research funding for Alzheimer's will reach only about $566 million, according to a recent article in the AARP Bulletin. The more time that passes without any treatments, the more the disease will cost Medicare and the 5.1 million Americans with the disease.
For the past 20 years, Penn has been on the front lines of understanding Alzheimer’s causes, treating patients and uncovering possible prevention strategies.
Recent work at Penn’s Center for Neurodegenerative Disease Research (CNDR) has identified compounds to prevent the formation of the protein tangles that lead to neuron death in AD. These compounds are currently being tested for their safety and eventual effectiveness in patients. In addition, researchers are also now working to identify biomarkers in the brain and body that could be signs of developing disease and thus potential targets for drugs to help slow or halt the development of this devastating disease.
“We are making progress,” said John Trojanowski, MD, PhD, a professor of Pathology and Laboratory Medicine and director of the Alzheimer’s Disease Core Center at the CNDR, an umbrella center that is leading national and international research in AD, Parkinson’s and a variety of other diseases caused by neurodegeration -- the death of neurons and brain function. Trojanowski is co-director of the CNDR.
Trojanowski and Virginia M-Y Lee, PhD, MBA, The John H. Ware 3rd Professor in Alzheimer's Research, professor of Pathology and Laboratory Medicine, director of the CNDR and Co-Director of the Marian S. Ware Center for Alzheimer's Drug Discovery Program, lead Penn’s efforts in neurodegenerative disease research.
This husband-and-wife team is founders of and has been at the helm of CNDR for more than 20 years. A 2011 ScienceWatch article ranked them as among the top one percent of neuroscience researchers.
This dynamic duo and their team of basic scientists, physicians, neurologists, geneticists, and patients were the first to discover, in 1991, the significance of the protein known as tau in the misfolding of proteins which form neurofibrillary tangles, one of the two hallmark brain lesions that cause Alzheimer’s. The discovery turned the AD research world on its head, as it was previously thought that plaques of amino acids known as amyloid beta were the only causes of the disease.
Misfolded tau proteins prevent the protein from carrying out its normal brain function. Its cell-to-cell spread contributes to the proliferation of the disease throughout patients’ brains.
Thanks in part to the work of the CNDR, it is now known that the two work in tandem – the tangles in the cell and the plaques outside the neuronal cells— that lead to the manifestation of AD. While tau is implicated in other neurodegenerative diseases, amyloid beta is thought to be specific to, and the primary cause of AD. In normal brains, amyloid beta leaves the neuron and passes quickly though tissues outside the cells, but in patients with Alzheimer’s, the amino acids accumulate and clump up in plaques in the brain, thus impeding normal brain function.
Amyloid beta leads to cognitive impairments and tau pathology is thought to be the trigger for neuron degeneration in AD. The current, most hopeful prevention efforts build on this understanding. The best hopes for drug treatments are those compounds that can halt the proliferation of amyloid beta and in turn, the genesis of tau tangles.
“These therapies all serve as great hopes for me, John and our entire team in finding a way to tame Alzheimer’s,” Lee said.
Lee, Trojanowski and the team at CNDR also discovered alpha-synuclein in Lewy bodies, most often present in Parkinson’s, but also implicated in 50 percent of AD cases, and TDP-43, a protein thought to play a role in the development of amyotrophic lateral sclerosis (Lou Gehrig's disease) and frontotemporal degeneration as well as AD.
The Penn Memory Center partners with CNDR, managing the care of patients with Alzheimer’s and other neurodegenerative diseases as well as pursuing patient-oriented research. The Memory Center’s care team provides educational materials and recruits patients for clinical trials, biomarker studies and helps evaluates quality of life and decision-making for patients and caregivers.
Penn research has made a significant contribution to the exciting place the field finds itself today. “We know where we want to go, we just need the resources to accelerate the pace of drug discovery to create a world without Alzheimer’s disease and related dementias,” Trojanowski said.