OMRF.org

Discoveries That Make a Difference

Are peptides all they’re cracked up to be?

by

Adam’s Journal

In my (deep sigh) seemingly never-ending odyssey to heal my torn hamstring, I recently visited a physician who suggested that I try peptides. I’ve heard a lot about them lately, but I confess I don’t really know what they are. Are peptides a safe and effective option for injuries like mine?

Dr. Scofield Prescribes

Yes, peptides seem to be all the rage these days. Wellness influencers, tech moguls and even our Secretary of Health and Human Services are trumpeting the promise of peptides for everything from skin care and building muscle to longer lives.

Peptides are short chains of amino acids – basically fragments of proteins. They occur naturally in our bodies and play many useful roles in our cells, including helping digestion, regulating blood pressure and reducing inflammation.

Peptides can also be synthesized and turned into medications. There are several peptide therapies approved by the U.S. Food and Drug Administration. Some that you might know are insulin and GLP-1 drugs. (Fun fact: the P in GLP-1 stands for peptide.)

Beyond these FDA-approved therapies is a much larger “gray market” of peptides. Until 2023, compounding pharmacies could make certain other peptides when prescribed by a doctor. But due to safety concerns, the FDA removed a group of them from the list that compounding pharmacies could make.

These peptides, which are marketed for a wide variety of health benefits and therapies, have largely been untested in humans. They’re primarily manufactured in China, and those who’ve analyzed them have found that what’s being advertised isn’t always what’s actually being sold to buyers. The products also can be tainted.

Health Secretary Robert F. Kennedy Jr. has declared himself “a big fan of peptides.” He says he has used peptides to treat injuries he’s suffered, “with really good effect.”

Kennedy announced that in July, the FDA will evaluate seven of the most popular ones. Most observers believe this signals that the agency will soon allow compounding pharmacies to make them again.

On the list are two peptides – known as BPC-157 and TB-500 – that have been shown in pre-clinical trials to combat inflammation and promote tissue healing.

A 2025 paper from researchers at the University of Utah looked at the research studies conducted with BPC-157. They determined that while studies involving animals and cell cultures, along with small human studies, suggested the peptide held potential to promote healing, “human data are extremely limited,” and “rigorous, large-scale trials are lacking.”

The data are even more limited on TB-500. A review of the two peptides in The American Journal of Sports Medicine this year noted that research studies had yet to generate reliable human data on the peptides’ safety, side effects, proper dosage, or which conditions they should – or shouldn’t – be used to treat.

Against this uncertain backdrop, I would strongly caution against using peptides. Unless and until large-scale human clinical trials demonstrate peptides’ safety and effectiveness, anyone who takes them is simply experimenting upon themselves.

–

Dr. Hal Scofield is a physician-scientist at the Oklahoma Medical Research Foundation, and he also serves as Associate Chief of Staff for Research at the Oklahoma City VA Medical Center. Adam Cohen is OMRF’s senior vice president and general counsel. Send your health questions to contact@omrf.org.

Bodywork: Protecting kids’ knees from sports injuries

by

Each week, OMRF Vice President of Research Dr. Rod McEver opens “Adam’s Journal” to answer a medical question from Adam Cohen, OMRF’s senior vice president & general counsel.

Adam’s Journal

I’ve heard that females are much more likely to suffer ACL injuries in their knees than males. Is this true? If so, why?

 

Dr. McEver Prescribes

The anterior cruciate ligament, or ACL, is one of the two main stabilizing ligaments of the knee joint. It connects the shin bone (tibia) to the thigh bone (femur) at the center of the knee.

The ACL limits forward motion and rotation of the lower leg. But it can tear when too much force is exerted on the knee or when the knee over-rotates. ACL injuries most frequently occur during sports, usually when landing from a jump or as an athlete stops suddenly or pivots.

Research has consistently found that females suffer ACL injuries at higher rates than males. For instance, in college athletes, one study determined that female basketball players suffer ACL tears at 3.5 times the incidence of their male counterparts and at 2.8 times greater rates in soccer. In high school soccer players, the numbers were quite similar, with ACL tears about three times higher in girls than boys.

The reasons for this are, alas, still unsettled. Scientists and physicians love hypotheses, and to explain this phenomenon there are many.

The most frequently cited potential culprit is females’ wider hip width. However, males actually have, on average, wider hips. Nevertheless, some have speculated that the important number is not absolute hip width but, rather, the ratio of hip width to thigh length.

Other potential contributors are female hormones like estrogen during the menstrual cycle, size and strength differences for males’ and females’ ligaments, and differences in surrounding muscle groups between the sexes.

While scientists continue to study the causes of this problem, we do know that starting strength, balance and control exercises as soon as kids begin playing sports can help prevent ACL injuries in both males and females.

If children learn early to avoid high-risk movement patterns – like landing with straight legs or on one leg – they’ll reduce their risk for this devastating injury.

–

Do you have a health query for Dr. McEver? Email contact@omrf.org and your question may be answered in a future column!

OMRF scientist uncovers clues about age and muscle loss

by

New findings from OMRF have revealed clues that could lead to new strategies to combat age-related muscle loss.

The study was led by OMRF scientist Benjamin Miller, Ph.D., and researchers from the University of Iowa. The biggest breakthrough came from identifying an age where the ability to regrow muscle after a period of loss is greatly impaired. Further, they show that these changes vary by muscle and not all muscles are the same.

The researchers looked at rats and found they could regrow muscle after a period of loss until 24 months of age, but at 28 months this ability dropped off. Miller said this translates to humans in their 70s.

The goal of the study was to better understand the two trajectories by which people lose muscle over time. The first occurs through the gradual loss of muscle that comes with aging. The second results from acute periods of loss that take place after situations like bedrest or following an injury. A better understanding of these two courses could lead to intervention strategies and treatment options.

“The gradual loss over time is something we all go through, but these other critical periods when you are bedridden that can have long-lasting consequences. You can lose muscle mass really quickly during periods of immobilization,” said Miller, a physiologist in OMRF’s Aging and Metabolism Research Program. “Young people have the ability to gain that back quite well, but this seems to be impaired in older individuals.”

This inability to regain muscle sets older people on a new trajectory of loss because they can never really rebound. This can be catastrophic for the elderly, leading to a loss of mobility and independence that often cannot be recaptured.

“Our lab is focused on learning how to maintain muscle, which is critical for maintaining independence and a healthy metabolism,” said Miller. “We want to keep people able-bodied for longer so they can get the most out of their years. This research will give us new targets to aim for toward this goal.”

The second significant finding was that changes with age or from atrophy differ from muscle to muscle. Miller said the results led to additional questions about the underlying mechanisms by which some muscles are maintained during aging, while others are not.

“From a public health perspective, this broadens our knowledge and shows us we need to consider muscles on a case-by-case basis,” said Miller. “This also identifies a critical period where, if someone has an extended period of inactivity, we need to target the regrowth and learn what we can do to intervene.”

The findings were published in the Journal of Cachexia, Sarcopenia and Muscle. OMRF scientists Justin Reid and Rick Peelor contributed to the research.

Slimy, squirmy creatures: the unsung heroes of medical research

by

Fish. Frogs. Worms.

While you’d expect to find them in your local pond, they’re also some of the biggest contributors to modern medical research. And there’s a reason these so-called “lower” organisms have been swimming, hopping and squirming their way into labs at the Oklahoma Medical Research Foundation: They’re key players in the war against disease.

“Humans are incredibly complicated and it’s difficult to do experiments with them, so we have to use animal models instead,” said OMRF researcher David Jones, Ph.D.

Jones relies on zebrafish, which grow to a length or one to two inches and are named for the horizontal stripes that run along their bodies, to research colon cancer and other diseases. “If you really want to know how something works, you have to study the simplest models possible so you can study them in-depth,” Jones said.

Jones is not alone in tapping these tiny creatures to learn about the human body. For decades, researchers have performed experiments with mice. But scientists are increasingly branching out to use other organisms—like fish, mice and frogs—to understand complex biological processes.

This trend has come about thanks to innovative technologies known as “functional genomics,” which enable scientists to study the biological functions of genes. “We can utilize powerful genetic tools and the animals’ short life cycles to understand these processes more economically and more quickly than ever,” said Jones.

The lessons scientists learn from other organisms can teach us a lot about ourselves, as we share a surprising amount of genetic material with some unlikely cousins. “All organisms are made up of cells, whether they’re a person, a fish or fruit. In fact, our genomes are 40 percent identical to a banana,” said Jones.

The zebrafish that Jones works with share 70 percent of humans’ genetic code. Their utility in experiments is enhanced by the fact that they reproduce frequently, are fully developed in a matter of days, and are transparent, allowing scientists to easily observe their developing cells.

“In two years, I learned more from zebrafish than I had learned in 18 years studying human cell lines,” said Jones.

In the lab next to Jones, his OMRF colleague David Forsthoefel, Ph.D., studies tissue regeneration in flatworms called planarians. “Because we have so many genes in common with planarians, we can essentially ask how regeneration works and look for ways to use this data in humans.”

Forsthoefel is hoping that clues he learns from the tiny worms, which have the ability to regenerate themselves and their organs completely, might lead to new help in treating conditions ranging from bowel disorders to paralysis. “It might be possible to improve our own regenerative abilities just by promoting or inhibiting the action of one or two genes,” said Forsthoefel.

Susannah Rankin, Ph.D., another OMRF researcher, uses frog eggs to study cell division. Her observations in amphibians could provide important information on how to prevent the development of tumors in humans.

“Now we can use these organisms to study thousands of genes and do it fast and at low cost,” said Jones.

While scientists typically receive plaudits when they make a new discovery, Jones thinks that fish, worms and frogs also deserve some of the credit. “We’ve already learned things we never would have by looking at humans or mice,” he said, “and these organisms have made it possible.”

OMRF research sheds new light on effects of aging in knee joints

by

Research from the Oklahoma Medical Research Foundation has identified new culprits that may be responsible for the development of arthritis.

The study found that growing older increases the production of a pair of inflammation-producing proteins. It suggests that targeting these inflammatory proteins might provide a path for future development of arthritis therapies.

The new findings, published in the Journal of Gerontology, provide a snapshot of age-related changes in a crucial area of soft tissue in the knee.

A team led by OMRF’s Tim Griffin, Ph.D., and Yao Fu, Ph.D., examined the knee joints of rats as they aged. In particular, the researchers studied the animals’ infrapatellar fat pad, the soft fatty tissue that lies beneath the kneecaps of both rodents and humans.

Scientists have known that these fat pads are a source of inflammation in osteoarthritic knees. And they’ve believed that this inflammation contributes to osteoarthritis, which occurs when cartilage breaks down and wears away.

“It’s actually the most common form of arthritis, often affecting the hips, hands and spine, in addition to the knees,” said Griffin. According to the Centers for Disease Control, an estimated 27 million Americans suffer from osteoarthritis.

Griffin and Fu wanted to look specifically at how aging affects inflammation in the fat pads. Griffin says he anticipated that as the animals grew older, the amount of inflammation produced by the fat pad and the size of the animals’ fat pads would increase.

“But our findings were not quite what we expected,” said Griffin. Specifically, the fat pads actually shrunk while producing higher levels of two inflammatory proteins.

“Our study suggests the fat pad is a contributor to a general increase in knee inflammation that occurs with age,” said Fu. This points toward future treatments to limit the inflammation, which might then prevent osteoarthritis from developing.

However, the researchers did find a benefit to aging in biological conditions that simulated an acute injury—such as a fall that causes damage to a joint. In this condition, the older fat pads decreased their production of leptin, a protein secreted by fat that also contributes to the break down of cartilage.

“We know there is acute inflammation that occurs after injury and can have long-term consequences,” said Griffin. “This study taught us that under certain conditions aging can actually limit the amount of leptin produced by the knee fat pad. This might help us develop new strategies to reduce post-traumatic osteoarthritis, a common cause of the disease in younger active adults.”

Janet Huebner, Ph.D., and Virginia Kraus, Ph.D., of Duke University also contributed to the research, which was supported by grants from the National Center for Research Resources (number RR018758), the National Institute of General Medical Sciences (number GM103441), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (number AR066828), and the Arthritis Foundation.

OMRF discovers cargo system that keeps brain cells on the right track

by

With the help of a simple little worm, an Oklahoma Medical Research Foundation scientist is unraveling the mysteries of a complex transportation system the brain uses to move the tiny cargoes that contribute to our perceptions, thoughts and memories.

Brain cells, or neurons, have long tentacles called axons, through which they communicate with one another and with muscle cells. Some axons reach lengths as long as 3 feet in humans. To deal with these long distances, neurons have developed an amazing system of tiny “train tracks” and “engines” to quickly carry cargo long distances in both directions. The cargoes consist of tiny membrane sacs called “vesicles” that provide the signals for thoughts and memories, as well as larger sacs called “organelles” that help the neuron grow or repair an injury.

OMRF’s Kenneth Miller, Ph.D., is seeking to understand how the cargo system is regulated to keep us thinking clearly, as well as how defects in the transport system contribute to neurological disorders.

Miller and his colleagues have discovered a new “conductor” that regulates the cargo movements in neurons. The conductor allows the tiny vesicle cargos that are important for our thoughts and memories to stay in axons where they are needed but sends the larger ones (organelles) back to the cell body of the neuron so they won’t clog up the axon or interfere with the signals that help us think and move.

However, Miller said the system can be regulated to allow the larger organelles to move into the axon when they are needed, for example, to help the neuron grow or recover from an injury.

Miller and his team made their discovery using C. elegans, a tiny roundworm with a simple nervous system. The new findings were published in back-to-back papers in the scientific journal Genetics.

“Neurons actively shuttle their cargo along tracks using motor proteins that essentially act as engines,” said Miller. “The motors literally walk along these tracks, shouldering their cargo. We have found a neuron-specific transmission system for regulating the connection between one of these motors and its cargo.”

Neurons have several kinds of motors that can move cargo outward, but only one, known as dynein, can move cargo back into the cell body. Miller and colleagues discovered a new function in neurons, which they named the CSS system. The CSS system seems to act as part of dynein’s transmission system, determining whether or not the motor engages with cargo. Miller noted that a recent study found that as many as 14 neuronal diseases are connected to the dynein motor.

“We still don’t understand the basis of a lot of neurological disorders, because we’re still learning how nerve cells work,” said Miller. “But this discovery gets us one step closer to revealing how the most complex cells in our bodies function at a molecular level. Once we understand how things are supposed to work at that level, we may be able to treat a person with a neurological disorder by targeting the malfunction with a drug or using new methods of gene therapy.”

“It’s remarkable how studies of a tiny worm that has a very simple nervous system can be the key to unlocking a very complicated process that nerves use,” said OMRF Vice President of Research Paul Kincade, Ph.D. “Every cell in the body has complex components, and in the case of neurons, it’s important to sort what goes out and what comes back. Miller has used very elegant experimental approaches to identify one of the key players in this intricate process.”

This research is funded by grant R01GM080765 from the National Institute of General Medical Sciences and the Oklahoma Center for the Advancement of Science and Technology grant HR14-003.

OMRF scientist shows potential ALS, traumatic brain injury link

by

Whether on the battlefield or playing field, trauma to the head has increasingly been shown to cause long-term damage to the brain.

Now, an OMRF scientist has completed a research project examining how traumatic brain injury (TBI) relates to degenerative brain disease. Specifically, OMRF’s Holly Van Remmen, Ph.D., and her colleagues looked at whether TBI affected disease progression in amyotrophic lateral sclerosis or ALS, better known as Lou Gehrig’s disease. There is evidence to suggest that TBI can increase the risk of ALS.

ALS is a progressive neurodegenerative disease affecting nerve cells in the brain and the spinal cord. As the nerve cells degenerate and die, it adversely affects the ability of the nervous system to control muscle movement, leading to paralysis and muscle wasting.

About 5,600 people in the U.S. are diagnosed with the disease each year. Patients live, on average, between two to five years from the time of diagnosis, and a cure has been very elusive.

“We were interested in learning if TBI would accelerate the progression of ALS in a well-characterized mouse model engineered to develop ALS,” said Van Remmen, who served as principal investigator on the project.

Van Remmen’s research team found that the mice with genetically induced ALS exposed to mild TBI had decreased coordination, muscle function and loss of grip strength, which points to evidence of a loss of natural reflexes. “Overall it only showed a few minor effects, but there were effects nonetheless,” she said.

According to Van Remmen, the loss of nerve supply to the muscles, which ultimately leads to the degeneration of cells, tends to be elevated when TBI is involved, as well. While the observable effects were minor, they can add to what is already a devastating condition.

“This research does not answer the question of whether suffering a traumatic brain injury can make you more likely to develop ALS, but it shows that the TBI can worsen the traits of ALS,” said Van Remmen.

It is possible, she said, that a more forceful head injury mimicking that seen in combat victims would yield more substantial progression in this already dramatic disease.

“This study represents the first time I think that anyone has shown changes in motor performance after TBI in mice with ALS,” said Van Remmen. “It reveals maybe that there is some measurable relationship between ALS and TBI.”

TBI contributes to nearly 30 percent of all injury deaths in the U.S. and results in approximately 2.5 million emergency room visits annually, according to the Centers for Disease Control and Prevention. Long-term effects of TBI can include memory loss, impaired coordination, loss of balance, impaired senses and serious emotional conditions such as aggression, anxiety and depression.

The new research was published in the journal Neuroscience. The research was funded in part by the Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship Grant (1F31NS080508-01), which was awarded to the paper’s first author, Teresa Evans, at the UT Health Science Center in San Antonio, as well as a VA merit grant for Van Remmen.

OMRF.org