The U.S. Department of Defense (DOD) recently awarded a three-year, $2.7 million grant to a team of biomedical engineers in the Cockrell School of Engineering at The University of Texas at Austin. The grant will be used to develop an injectable treatment that may help older Americans and others — like diabetics — with peripheral ischemia, or restricted blood flow to the limbs.
Dr. Aaron Baker, an associate professor in the Department of Biomedical Engineering, and colleagues will receive the grant from the DOD’s Congressionally Directed Medical Research Programs. It will support the development of an ischemia treatment and help move the treatment through pre-clinical assessment to potentially bring into human trials.
The research team developed a regenerative gel that can be injected into the lower limbs. This gel contains proteoglycans, proteins that contain sugar, and a growth factor to incite the growth of blood vessels and to restore blood flow.
“Ischemia is a huge problem for people with diabetes and leads to many issues, including non-healing wounds and the eventual need to amputate limbs, in severe cases,” Dr. Baker said in a news release. “The purpose of our research is to develop a successful therapy, a gel that can be injected into the leg so blood vessels can grow back.”
Peripheral vascular disease (PVD), which can cause peripheral ischemia, refers to disorders in blood vessels outside the heart and brain, and often to a narrowing of vessels that carry blood to the legs, feet, arms, stomach or kidneys. There are two types of PVD: functional PVDs, which do not involve defects in blood vessels’ structure and whose symptoms can be come and go, and organic PVD, caused by structural changes in the blood vessels through inflammation, tissue damage, and the like.
Medicine, bypass surgery, and physical therapy to unclog vessels or arteries can temporarily relieve PV, and peripheral ischemia, but there are no long-term treatment options.
“Our treatment is different from existing options in that you are going to grow new, small vessels that will take the place of the old ones that aren’t working well,” Dr. Baker said.
A number of researchers have been working to deliver growth factors to prompt the growth of blood vessels (angiogenesis), but therapies in clinical trials have only achieved a partial success in patients. The UT Austin team suggested that these therapies lacked a key protein to trigger the growth factors that build blood vessels. In experiments, the team found that mice with diabetes were lacking proteoglycans — proteins that provide signals to growth factors to grow blood vessels.
“The idea was to give a growth factor that induces angiogenesis, and also to find the missing piece, proteoglycan, which makes it work,” Dr. Baker said.
Using the gel in mice with diabetes and ischemia, the researchers were able to successfully grew new blood vessels. The mice had a 85 percent blood vessel recovery, compared with the 60 percent recovery reported by other growth factor-based treatments. The results were recently published in the journal Advanced Healthcare Materials, in the study “Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes“.
“We believe our treatment could also be used as a platform to treat the complications of diabetes, including non-healing wounds and myocardial ischemia, which causes obstructions in the heart,” Dr. Baker said.
The research team is planning to optimize the patent-pending treatment, and to determine the correct dosing and delivery method before moving it into human clinical trials.
Each year in the United States, more than 3 million cases of PVD are reported. People with diabetes, those age 65 or older, and smokers are at increased risk for the condition. If not treated, peripheral ischemia can lead to gangrene and amputation.