I have been working on "genomic instability in the body" research theme. The research has been done mostly in the context of carcinogenesis and its prevention. But later on, "genomic instability in the body" turned out to be involved in many other biological events including aging.
Then, after my mother's diagnosis in 2015, I got personally motivated to study Alzheimer's disease, which led to the study in this press release.
This is a part of an ongoing story. I will follow this up.
#####
Stephenson Cancer Center Investigators Apply Cancer Research Tools
to Help Unravel Alzheimer’s Disease
to Help Unravel Alzheimer’s Disease
Investigators at the Stephenson Cancer Center at the
University of Oklahoma Health Sciences Center are utilizing cancer research
methods and tools to advance the understanding of Alzheimer’s disease. Results
of these efforts have been published in Aging
Cell, a highly regarded journal in the field of aging research.
“In 2015, my mother was diagnosed with Alzheimer’s disease,”
said Dr. Hiroshi Yamada, the lead author for the study. “As I started to learn
about the current status of Alzheimer’s disease studies and clinical practice,
I was surprised to learn that over 98 percent of about 400 Alzheimer’s drug
candidates tested in clinical trials have failed.”
There is no current cure for Alzheimer’s disease, which is a
leading cause of cognitive impairment and death among people aged 65 and older.
Existing drugs can help neuronal function and delay progress, but they do not
address the root cause of the disease. The Alzheimer’s Association estimates
that 64,000 Oklahomans age 65 or older live with Alzheimer’s dementia – a
number projected to increase to 76,000 by 2025.
Yamada, a cancer researcher by training, learned that genomic
instability, his specialty, was potentially involved in Alzheimer’s disease.
His cancer-focused work has looked at the effects of genomic instability, or
the high frequency of genetic mutations, within the body. His research
specifically focuses on how genomic instability causes molecular changes, influences
biochemical and immune defense systems against cancer, and eventually causes
proneness to certain types of cancers.
Yamada decided to investigate whether genomic instability has
a role in causing or facilitating Alzheimer’s disease. To test this hypothesis,
he utilized preclinical models of genomic instability developed for cancer
research.
One of his experimental models showed spontaneous accumulation
of amyloid-beta, a protein known to contribute to Alzheimer’s onset and progression,
at old age. This was different from existing studies for Alzheimer’s disease,
which have been based on early-onset models, depending on forcible expression
of amyloid metabolism component(s) in the brain. These existing models will
develop amyloid-beta plaques and other pathological features, but whether they
recapitulate molecular events involved in spontaneous, late-onset Alzheimer’s
disease, which is over 95 percent of cases, is questionable.
Much of Alzheimer’s disease drug development has been based
on an assumption that drugs that work on early-onset Alzheimer’s disease will
work on late-onset Alzheimer’s disease. With many costly failures in clinical
trials, some pharmaceutical companies have withdrawn from Alzheimer’s disease
drug development, despite the unmet clinical need. Some speculate that the high
failure rate in clinical trials may be partially attributed to current drug
test models that may not properly represent some aspects of spontaneous,
late-onset Alzheimer’s disease.
Dr. Yamada’s insights point to a link between chromosome
instability and the development of Alzheimer’s disease. His new model, focused
on old age, is thought to be the first genetically defined model for
spontaneous late-onset Alzheimer’s disease. This will be a useful tool with
which to test Alzheimer’s disease drug candidates, as well as to find
biomarkers for Alzheimer’s disease risk assessment or diagnosis.
Yamada’s research group is now hypothesizing that certain
classes of cancer drug may be able to interfere with amyloid-beta accumulation.
They are in the process of proposing tests. If the “drug repurposing” approach
proves effective, the drug could potentially be available to clinics in 3-7
years, instead of the normal 15-20 years that it takes to develop a drug from
scratch.
“Once an effective drug for a difficult disease is discovered, medical practice will change,” said Yamada. “We are hopeful that our study will lead the charge for Alzheimer’s disease treatment in clinics.”
In addition to Yamada, Stephenson Cancer Center members
involved in the study include Dr. Chinthalapally V. Rao, leader of the
Experimental Medicine and Developmental Therapeutics Program, and Dr. Adam
Asch, Stephenson Cancer Center Deputy Director and Section Chief for Hematology
/ Oncology at the OU College of Medicine.
###
About the
Stephenson Cancer Center
The Stephenson Cancer Center at the University of Oklahoma
is the only National Cancer Institute (NCI)-Designated Cancer Center in
Oklahoma. Less than 2 percent of cancer centers nationally have earned this
prestigious and highly competitive accreditation for outstanding patient care
and research. The Stephenson Cancer Center is the largest oncology practice in
the state, with more than 70 board-certified oncology physicians and a large
team of advanced providers and supportive care specialists delivering the
highest standard of patient-centered, multidisciplinary care for every type of
cancer. The Stephenson Cancer Center currently ranks number one among all
cancer centers in the nation for the number of patients participating in
NCI-sponsored treatment trials, and it is one of only 30 lead centers in the
NCI’s National Clinical Trials Network. The Stephenson Cancer Center is
Oklahoma’s leading cancer research organization, with 115 research scientists
working to eliminate cancer through conducting innovative basic, clinical and
population-based research. These researchers are working on 225 cancer research
projects supported by $44 million in annual grant funding from the National
Institutes of Health and other sponsors. With a legislatively mandated mission
to provide statewide leadership in addressing Oklahoma’s cancer burden, the
Stephenson Cancer Center supports numerous outreach, education and screening
programs in partnership with the Oklahoma Tobacco Settlement Endowment Trust,
the American Cancer Society, the Susan G. Komen Foundation, and Oklahoma’s
Tribal Nations among many other aligned organizations.
| Link to the Press Release article/website: https://stephensoncancercenter.org/News/Article/TabId/6745/ArtMID/17400/ArticleID/7812/Stephenson-Cancer-Center-Investigators-Apply-Cancer-Research-Tools-to-Help-Unravel-Alzheimer%E2%80%99s-Disease.aspx Link to original research article: https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.12797 |
