With the support of the National Institute on Drug Abuse, scientists at Wake Forest School of Medicine have been working to find a safe, non-addictive pain killer to help fight the current opioid crisis in this country. They may have done just that, though in an animal model.
Known as AT-121, the new chemical compound discovered by study co-author Nurulain Zaveri, PhD, of Astraea Therapeutics, has dual therapeutic action that suppresses the addictive effects of opioids and produces morphine-like analgesic effects in non-human primates.
“In our study, we found AT-121 to be safe and non-addictive, as well as an effective pain medication,” said Mei-Chuan (Holden) Ko, PhD, professor of physiology and pharmacology. “In addition, this compound also was effective at blocking abuse potential of prescription opioids, much like buprenorphine does for heroin, so we hope it could be used to treat pain and opioid abuse.”
The findings were published in August in the journal Science Translational Medicine.
In the study, the researchers observed that AT-121 showed the same level of pain relief but at a 100-times lower dose than morphine. At that dose, it also reduced the reinforcing effects of oxycodone, a commonly abused prescription drug.
Next steps include conducting additional preclinical studies to collect more safety data.
The National Institute on Aging, part of the National Institutes of Health (NIH), has awarded Wake Forest School of Medicine researchers a five-year grant worth more than $18 million to study the connections between heart health and brain health among participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
The research will be led by Timothy Hughes, PhD, assistant professor of gerontology and geriatric medicine, and Kathleen Hayden, PhD, associate professor of social sciences and health policy at the Wake Forest Alzheimer’s Disease Research Center, along with José Luchsinger, MD, of Columbia University Medical Center in New York.
Hughes said the team will track vascular disease at its earliest stages, determine how it relates to brain health in aging and look at whether heart health may explain increased incidence of Alzheimer’s and other dementias among different racial and ethnic groups.
The researchers plan to enroll approximately 3,000 MESA participants from its six study sites across the United States beginning in early 2019.
The National Institutes of Health (NIH) has awarded $8 million to Wake Forest Baptist to study cognitive decline and impairment in older adults with type 2 diabetes who are overweight or obese.
“It is critical to understand the role of lifestyle intervention for the treatment of type 2 diabetes and obesity,” said one of the study’s principal investigators, Mark Espeland, PhD, professor of public health sciences at Wake Forest Baptist. “Together, these two conditions nearly double one’s risk for Alzheimer’s disease and related dementias.”
The four-year study, part of the NIH’s Action for Health in Diabetes, will be led by Espeland, Kathleen Hayden, PhD, associate professor of public health sciences at Wake Forest Baptist, and José Luchsinger, MD, of Columbia University. The study will build on earlier findings that intensive lifestyle intervention in overweight older adults with diabetes was associated with a 30 percent decrease in cognitive impairment. However, this potential benefit was not firmly established, necessitating additional research.
The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health (NIH), has awarded Wake Forest Baptist two five-year grants, each worth approximately $1.5 million, to participate in two nationwide clinical trial networks.
Under one grant, Wake Forest Baptist will become one of 25 clinical sites in the Network for Excellence in Neuroscience Clinical Trials. Known as NeuroNEXT, the network was created in 2011 to make neuroscience clinical trials more efficient and to advance the development of new treatments for neurological diseases.
Through another grant, Wake Forest Baptist will be one of 29 regional centers in NIH StrokeNet, established in 2013 to develop, promote and conduct high-quality, multi-site clinical trials focused on stroke prevention, treatment and recovery. As a regional center, Wake Forest Baptist will coordinate the network-related activities of its partners in the Western North Carolina StrokeNet: Novant Health Forsyth Medical Center in Winston-Salem, Novant Health Presbyterian Medical Center in Charlotte and Asheville-based Mission Health.
Wake Forest Baptist is the only North Carolina institution participating as a clinical site or regional center in these network.
Facial wounds or burns could one day be treated with skin tissue regenerated with the use of a 3-D bioprinted BioMask created by Wake Forest Institute for Regenerative Medicine (WFIRM) scientists.
Skin injury or burns to the face are difficult to treat due to the varied contours and complex movement of the muscles. Current strategies to treat extensive facial wounds and burns are limited to the use of skin grafts and skin substitutes which can often lead to scarring, infection or graft failure.
In recent decades, regenerative medicine and tissue engineering has emerged as an effective method for skin regeneration. Bioengineered skin substitutes can be created from both natural and synthetic materials and are most commonly placed directly on the skin wound site, but they are limited in size and some require a lengthy preparation time. And, with traditional skin grafts, many burn patients do not have enough unburned skin to harvest grafts.
The BioMask could change that. This proof-of-concept study, published online in the journal Bioprinting, involved the novel strategy of a customized, bioengineered skin substitute combined with a wound dressing layer to snugly fit onto a facial wound to regenerate skin.
“For patients who suffer from disfiguring facial wounds, the BioMask could one day be used as an effective treatment that would greatly improve their quality of life,” said lead author Sang Jin Lee, PhD, associate professor of regenerative medicine at WFIRM.
Wake Forest Baptist Medical Center, Wake Forest University and Winston-Salem State University have received a two-year grant worth approximately $510,000 to support their continued participation in the largest-ever study of sports-related concussion.
The NCAA-Department of Defense Concussion Assessment, Research and Education (CARE) Consortium study is designed to examine the incidence and effects of concussion and repetitive head-impact exposure among student-athletes of both sexes at colleges and universities in all NCAA divisions. Wake Forest and Winston-Salem State are among the 30 NCAA members participating in the study.
Since the summer of 2016 Wake Forest Baptist personnel have directed comprehensive baseline screening for concussion on all athletes (including cheerleaders) at Wake Forest and Winston-Salem State and conducted follow-up evaluations on all those who have suffered concussions.
The researchers are now also collecting saliva samples from the athletes for DNA analysis to determine if there are any differences between the DNA of those who have suffered concussion and those who have not.
Although immunotherapy is seen as a very promising treatment for cancer, currently only 20 to 30 percent of patients respond positively. Being able to identify the people most likely to benefit from the costly therapy is a Holy Grail for oncologists.
In findings published online in JAMA Oncology, scientists at Wake Forest Baptist reported a new molecular biomarker for gastric cancer, which is the leading cause of cancer-related deaths worldwide.
Despite progress in the eradication of the bacteria helicobacter pylori, the major cause of gastric cancer, as well as earlier cancer diagnosis, the five-year survival rate for gastric cancer remains less than 30 percent.
“Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities,” said Wei Zhang, PhD, the Hanes and Willis Family Professor in Cancer Biology at Wake Forest Baptist and lead author of the study. “More potential markers are urgently needed to help oncologists decide which patient would benefit from this promising new treatment strategy.”
Probiotics seem to be everywhere—in yogurt, pickles, bread, even dog food. But there’s one place that may surprise you: There are probiotics in dirty diapers. That’s right—baby poop.
Wake Forest School of Medicine scientists have developed a probiotic “cocktail” derived from gut bacteria strains found in infant feces that may help increase the body’s ability to produce short-chain fatty acids.
“Short-chain fatty acids are a key component of good gut health,” said the study’s lead investigator, Hariom Yadav, PhD, assistant professor of molecular medicine at Wake Forest School of Medicine. “People with diabetes, obesity, autoimmune disorders and cancers frequently have fewer short-chain fatty acids. Increasing them may be helpful in maintaining or even restoring a normal gut environment, and hopefully, improving health.”
Findings were reported online in August in Scientific Reports, a Nature publication.
New research shows that the breast gland has a microbiome, and like the previously studied gut microbiome, it too can be affected by diet, according to scientists at Wake Forest School of Medicine.
“Being able to shift the breast microbiome through diet may offer a new approach to preventing breast cancer or at least reducing the risk,” said the study’s lead author, Katherine Cook, PhD, assistant professor of surgery – hypertension and cancer biology.
Published in the journal Cell Reports, the study utilized a well-established non-human primate model of women’s health to compare the effects of a Western diet to a Mediterranean diet on breast tissue. Female monkeys were fed a specially prepared diet that mimicked either a high-fat Western diet or a plant-based Mediterranean diet for two-and-a-half years, which is equivalent to about eight human years.
The group on the Mediterranean diet was found to have a distinctly different set of bacteria in their breast tissue than those on the Western diet. Consuming the Mediterranean diet led to about a 10-fold increase of mammary gland lactobacillus, a bacteria shown to decrease breast cancer tumor growth in preclinical models. The Mediterranean diet also resulted in more bile acid metabolites in the breast tissue, which may reduce breast cancer risk.
Research Funding
Research reported on in this publication was supported by the following grants from the National Institutes of Health (NIH):
Scientists Take Big Step Toward Finding Non-addictive Pain Killer: NIH, National Institute on Drug Abuse grants R01DA032568, R01DA027811, R44DA042465, R21DA040104 and R21DA044775. Additional support: U.S. Department of Defense W81XWH-13-2-0045.
Bioengineered BioMask Offers Promise for Healing Facial Skin Injuries: NIH grant 1P41EB023833-01.
New Evidence Found for Role of Diet in Breast Health: Grant to Carol Shively from the National Heart, Lung and Blood Institute R01HL087103. Additional support: Chronic Disease Research Fund (KLC), American Cancer Society Research Scholar grant RSG-16- 204-01-NEC (KLC), a Susan G. Komen Career Catalyst Research grant CCR18547795 (KLC) and the Prevent Cancer Foundation (KLC).
A Good Source of Beneficial Probiotics: Baby Poop?: Center for Diabetes, Obesity and Metabolism; the Kermit Glenn Phillips II Chair in Cardiovascular Medicine; the NIH-funded Claude D. Pepper Older Americans Center P30AG12232, R01AG18915, R01DK114224. Additional support: Clinical and Translational Science Center UL1TR001420 at Wake Forest School of Medicine; and the Department of Defense PR170446.