Research
VET MED-ENGINEERING COLLABORATION
WORKING TO IMPROVE WOUND HEALING FOR HORSES
Stem cell therapy is an emerging medical technology popularly used in the equine industry to treat horses for a variety of athletic injuries. The regenerative medicine technique uses cells from the horse’s own body to repair and speed up healing in such injuries as bowed tendons and torn ligaments, and theoretically, make the healing bond stronger.
A collaborative research program involving College of Veterinary Medicine scientists and colleagues from Auburn’s Samuel Ginn College of Engineering has isolated endothelial progenitor cells in horses and is developing engineered biomaterials as a medium for delivering these cells as stem cell therapy to heal distal limb wounds.
Stem cells are immature cells that do not yet have a specific job in the body, explained Dr. Anne Wooldridge, an associate professor of Equine Internal Medicine in the Department of Clinical Sciences and one of the principal investigators in the research. They can form into a particular type of cell, but they must be directed to the target and held intact long enough to survive, bond, and turn into the specific type of cell desired. Endothelial progenitor cell (or EPC) is a term that has been applied to multiple different cell types that play roles in the regeneration of the lining of blood vessels.
“This is the first research initiative to isolate these EPCs in horses, and we are using our interdisciplinary expertise to develop new regenerative therapies for horses that leverage the use of stem and progenitor cells combined with engineered biomaterials as the drug delivery medium through injection,” Dr. Wooldridge said.
Adequate blood flow to a wound is vital to the healing process. As runners, jumpers, prone-to-be kickers and large, heavy animals, horses tend to sustain severe cuts and other serious wounds in the distal area — the leg region below the knee and hock, Dr. Wooldridge added. Because the distal area of a horse is mostly bone and tendon, it does not contain much muscle to carry blood to the wound to promote healing. Thus, such wounds are often quite difficult to heal. Through the engineering partnership, the researchers have developed a promising way toward a feasible wound healing treatment procedure.
“The engineered biomaterials are hydrogels that we are developing in our lab,” said co-principal investigator Dr. Elizabeth Lipke, the Mary and John H. Sanders associate professor in the Department of Chemical Engineering. “They protect and hold these cells (EPCs) together to ensure that they reach their target and remain intact in order to form the type of regenerative cell desired.”
Although the EPC therapy structure is microscopic, the example used simplistically to illustrate its appearance is a gelatin fruit salad. “Think of the fruit as the cells and the gelatin as the hydrogel scaffolding that holds them intact,” Dr. Lipke said.
The group’s work, which has been underway for about six years, is grant supported by the Grayson Jockey Club Research Foundation with two primary goals: 1) to isolate the EPCs in the horse and 2) to improve ways to deliver them as stem cell therapy to enhance distal limb wound healing.
“We have isolated the cells,” Dr. Wooldridge said. “We have improved the success rate of the treatment method, and we have evidence in our clinical model that wounds treated in this manner do heal faster.”
The team is analyzing its research data and preparing for next steps. They hope, ultimately, to develop a medical treatment that is commonly available to the equine industry.
During the six years of their research, Drs. Wooldridge and Lipke together have mentored one master’s student, three doctoral students, four undergraduate students, one Morris Animal Foundation veterinary scholar and four Merial summer scholars. Other members of this research effort include Dr. Fred Caldwell, an associate professor of Equine Sports Medicine and Surgery, and Dr. Randolph Winter, an assistant professor in veterinary cardiology, who is completing his Ph.D. at the College of Veterinary Medicine.
A microscopic image of their research was featured on the cover of the February 2017 issue of AJVR (the American Journal of Veterinary Research).
ONE DISEASE. ONE MEDICINE. ONE AUBURN FAMILY.
The diagnosis of cancer in a loved one—whether human or animal—is difficult and challenging. Research by faculty through the Auburn University Research Initiative in Cancer seeks to find new cancer treatments for both animals and humans.
Dr. Bruce Smith, a professor of pathobiology at the College of Veterinary Medicine and AURIC’s director, leads a university effort to find cures for cancer through the work of researchers across Auburn.
The focus of Dr. Smith’s cancer research is osteosarcoma, the most common primary bone tumor found in dogs. It accounts for up to 85 percent of all malignancies originating in the skeleton. Osteosarcoma primarily occurs in middle-aged to older dogs, with a median age of seven years.
In humans, however, it is most often found in teenagers, as was the case in 2011 when Scott Shockley was diagnosed with the rare pediatric bone cancer.
With a competitor’s heart and an unmatched excitement for life, Shockley and his family were, like everyone who receives a cancer diagnosis, heartbroken and shocked.
And while medical treatments and doctor appointments became a part of his life, so did Auburn.
“Scott’s greatest passion was playing sports, being part of a team, and competing at a high level,” said Scott’s dad, Steve Shockley.
While attending high school, The Walker School in Marietta, Ga., Shockley was a three-sport athlete lettering in baseball, football, and basketball, and was a nationally ranked long snapper. He received numerous athletic awards, including Pitcher of the Year, was Homecoming King and a member of Walker’s Peer Leadership and Cobb County Youth Leadership.
When Shockley enrolled at Auburn in 2012, his love of sports didn’t waiver and, during his freshman year, he became a manager for the Tigers’ baseball team.
“Scott felt like Auburn was the place for him, and he loved Auburn,” Steve Shockley said. “He made many new friends and felt right at home.”
Although Scott’s cancer returned and he had to take classes online while receiving treatments in Atlanta, he kept in touch with baseball players and coaches and was able to join them for a few home games.
“Scott came in with a positive attitude and a great work ethic,” said Scott Duval with Auburn Athletics. “He was a perfect fit within the baseball program from day one and immediately became ‘one of the guys.’
“Despite the challenges he faced, he always had a smile on his face. He was friendly and made others feel special and appreciated.
“Those are the reasons he made such an impact in such a short period of time with us [Auburn Baseball]. And those are the reasons his parents are close to the program to this day, because of Scott’s impact on others.”
Sadly, Scott Shockley died in July 2013 after a 26-month battle with the disease.
Seeking a way to help other families suffering from the disease and to fulfill Scott’s wishes, the family established the Scott Shockley Foundation in 2014 to support research and find a cure for osteosarcoma, as well as provide awareness about early detection and treatment.
After learning about Dr. Smith’s research, the Shockley Foundation awarded a research grant to Dr. Smith to move research toward a cure.
Scott’s mother, Terriann Shockley, said the family and the foundation board were supportive after learning about Dr. Smith’s research because of the need for new treatment options for osteosarcoma patients.
“The chemotherapy treatment used today has not changed in the past 30 years,” she said. “Funding this research seemed fitting because of Scott’s love for his Brittany Spaniel, Daisy, and many connections to Auburn.” Scott’s sister, Stacy, is a 2012 alum; as was his oncologist, Dr. Thomas Cash; he had several friends who attended or are attending Auburn; and, retired professional baseball pitcher and AU alum Tim Hudson’s family foundation awards a yearly scholarship to a baseball manager in memory of Scott.
AURIC and the Scott Shockley Foundation were recognized by the college and Auburn Athletics during pregame ceremonies before a packed house at Plainsman Park this past spring. Steve Shockley threw out the ceremonial first pitch, and the family and the college were recognized for their commitment to finding a cure.
Dr. Smith’s current research uses an oncolytic virus which attacks and kills cancer cells without harming healthy cells. Initial clinical trials in dogs with osteosarcoma showed promise, and Dr. Smith and his group now are designing new and more potent second-generation viruses.
His research is a collaboration with Andrew Hessel, a distinguished research scientist with Autodesk Inc. The team is working to advance cancer treatment by tailoring the virus to each patient.
Hessel’s research focuses on “synthetic biology,” essentially “printing” DNA, and in the process, customizing the strands, creating personalized oncolytic viruses.
While moving to human clinical trials with this method is still a ways off, Dr. Smith hopes that this method of customizing and printing viruses can be achieved within a year. The grant from the Shockley Foundation will be used to identify genes within osteosarcoma tumor cells that can be targeted by the virus.
Despite the long road ahead, Dr. Smith is optimistic about the potential for the research to give patients, both human and animal, hope for a disease that affects so many.
“It’s amazing: we see dogs with cancer, and people are surprised. Dogs get cancer at the same rates that humans do, and often the same types,” Dr. Smith said. “The research Andrew and I are doing ties directly to the concept of One Medicine.
“This research has the potential to shift the paradigm.”
PROMISING THERAPY FOR FATAL GENETIC DISEASES IN CHILDREN NEARS CLINICAL TRIALS
COLLEGE OF VETERINARY MEDICINE, UMASS MEDICAL SCHOOL TO TEST GENE THERAPY TREATMENT FOR TAY-SACHS, SANDHOFF DISEASES
Researchers at the College of Veterinary Medicine and UMass Medical School are nearing human clinical trials on a genetic therapy for two rare neurological diseases that are fatal to children.
The scientists, in collaboration with a physician at the National Institutes of Health (NIH), are seeking approval from the U.S. Food and Drug Administration (FDA) to test a gene therapy treatment for Tay-Sachs and Sandhoff diseases, genetic disorders in a category known as lysosomal storage diseases.
Tay-Sachs and Sandhoff are inherited neurologic diseases that occur when genetic mutations prevent cells from producing enzymes needed to break down and recycle materials. Without these enzymes, the materials accumulate to toxic levels, slowly destroying the nervous system. The researchers are working on a gene therapy to correct the enzyme deficiency using adeno-associated virus (AAV) vectors.
The average life expectancy for children with infantile Tay-Sachs or Sandhoff disease is only three to five years. There is currently no treatment. The gene therapy in development has shown promise in animal models of these diseases by extending lifespans by up to four times those of untreated animals.
“The proof-of-concept studies in affected animals are compelling, and the FDA provided a clear path of remaining experiments needed to seek approval for human clinical trials,” said Doug Martin, Ph.D., professor at the College of Veterinary Medicine’s Scott-Ritchey Research Center. “We now need the funding to complete the studies.”
The animal phase of toxicity studies necessary to demonstrate the safety of the gene therapy for Tay-Sachs and Sandhoff diseases has been completed with the support of the National Tay-Sachs & Allied Disease Association and the Cure Tay-Sachs Foundation.
“Too many children with Tay-Sachs and Sandhoff have died since we started this project. The time has finally arrived to push back on these diseases,” says Miguel Sena-Esteves, Ph.D., associate professor of neurology at UMass Medical School. “Our single-minded goal is to get a safe and potentially effective therapy to patients and their families as quickly as possible.”
“Hopefully, once the news gets out that we are this close to human clinical trials, fundraising efforts will be sufficient so we can complete the IND-enabling studies and proceed to human clinical trials,” said Heather Gray-Edwards, DVM, Ph.D., assistant professor at the College of Veterinary Medicine.
Additional funding of $1.2 million is being sought to complete the safety studies, production of clinical grade AAV, and regulatory filings.
CANCER RESEARCHER RECEIVES GRANT
GRANT WILL SUPPORT FELINE TREATMENT STUDIES
Dr. Michelle LaRue, a resident in the Oncology Service, has received a grant from the Veterinary Cancer Society to support her research in feline cancer.
Dr. LaRue has been involved in her investigations for the past year-and-a-half. “I am conducting research in the hope of expanding our knowledge about feline cancer and its treatment,” she said.
Her focus is on T-regulatory cells (T-regs), which are critical to the maintenance of immune cells that help to prevent autoimmune diseases such as Lupus and various forms of cancer. “T-regulatory cells are present in everyone and in all species,” Dr. LaRue said.
T-regs typically are more evident around cancerous tissue and in patients’ blood, Dr. LaRue explained. High levels of T-regs in the tumor microenvironment are associated with poor prognosis in many cancers, such as ovarian, breast, renal, and pancreatic cancer. Indications suggest that T-regs suppress certain cells and hinder the body’s immune response against the cancer.
“We know that T-regulatory cells are increased in humans, dogs and rats with cancer,” Dr. LaRue said. “We do not, however, have as much information about this concerning feline cancer.”
Dr. LaRue’s objective through her research is to answer the questions:
1) Do T-regulatory cells increase in feline cancer patients as they do in other animal models?
2) If so, can they be decreased to help target and combat cancer cells in feline patients?
“We know that certain kinds of treatments will decrease those [T-reg] cells,” Dr. LaRue said. “If this research shows what we hope, we will better know what treatments to use.”
Cats are vastly different from dogs in the types of diseases and viruses that attack their systems, Dr. LaRue explained. Cats are subject to FIV (feline immunodeficiency virus) and FeLV (feline leukemia virus) which can be present in their DNA and cause decreases in their immune response. The field of feline oncology lacks information and knowledge about treating these and other feline-specific diseases.
“Hopefully, we will be able to use our results as a proof-of-concept study and to discover if these T-regulatory cells show similar responses and changes in cats as they do in other animal cancer patients,” Dr. LaRue said.
Dr. LaRue is collaborating with researchers at North Carolina State University, using its flow cytometry lab to examine DNA to categorize cell markers that identify certain types of cancer. She is in the process of enrolling patients for her research. Enrollment inquiries should be made to the Oncology Service at the College of Veterinary Medicine, 334.844.4690.
The Veterinary Cancer Society (VCS) was formed in 1976 by a small group of veterinarians who wanted to establish a professional organization dedicated to veterinary oncology. VCS is a non-profit educational organization incorporated in Illinois. Its more than 800 members include specialists in medical, surgical, and radiation oncology, internists, pathologists, pharmacologists and general practitioners worldwide.
Dr. LaRue received her DVM from Texas A&M University. She completed an internship for small animal medicine and surgery at Auburn, and a medical oncology internship at Louisiana State University. Following her residency at Auburn, Dr. LaRue plans to enter specialty-focused private practice.