Illustration by Aneri Pandya.

Particles on the Cusp of Type I Diabetes Prevention

Since it was first extracted from a dog’s pancreas in 1922, insulin has transformed Type I diabetes from a fatal condition to a livable chronic condition. Despite the last century’s astounding progress in both the methods for refining insulin and technologies for delivering it, Type I diabetes remains only a ‘treatable illness.’ While genetic factors underlying the disease have been identified, there are currently no methods to prevent it. A local company called OneVax is looking to change that.

Based at the Florida Innovation Hub at the University of Florida, OneVax is working to develop a vaccine that will curtail the autoimmune response in Type I diabetes – effectively preventing the disease process.

In 2012, an interdisciplinary group of scientists from the university’s Diabetes Center of Excellence founded OneVax after receiving a Small Business Innovation Research grant from the federal government.

The company draws on the various backgrounds of the involved primary investigators – Mark Atkinson, PhD, Todd Brusko, PhD, and Clive Wasserfall, MS – in Type I diabetes research and biomaterials technology from the laboratory of Benjamin Keselowsky, PhD.

Type I diabetes is caused by an autoimmune response – when the body’s own immune system acts against it – towards the beta cells in the pancreas. These beta cells are located in spherical clusters scattered throughout the pancreas. Once they’re attacked and destroyed, the pancreas can no longer secrete insulin, a hormone essential to processing blood sugar, or glucose. Type II diabetes, on the other hand, is caused when the body loses sensitivity to insulin. A key distinction is that Type I diabetes requires life-long insulin injections, whereas Type II can often be controlled with oral agents, diet and lifestyle changes.

Traditional vaccines protect against harmful foreign bacteria and viruses by priming the body’s immune system to recognize and eliminate threats early in the infection process. However, OneVax is working on a ‘negative vaccine’ model for Type I diabetes – one that acts to curb the body’s autoimmune response against the beta cells in the pancreas.

“The exciting part was joining the field of immunology with biomaterials and utilizing biopolymers to modulate immune responses in ways that hadn’t really been done before,” Brusko said.

“[In] a typical vaccine, there’s a soluble formulation that’s rapid release,” he said. “And the advantage to our technology is that you get a localized time release of these factors over a period of days to weeks so that you get continuous exposure to the key elements.”

The investigators have developed a platform of technologies to deliver these ‘key elements’ via nanoparticles made of PLGA, a polymer also used in dissolvable surgical stitches.

In a broad sense, the immune system consists of two branches: the effector branch, which recognizes and eliminates foreign pathogens (e.g., bacteria and viruses), and the regulatory branch, which keeps the effector in check and prevents damage to the body’s tissues and organs. Autoimmunity occurs when the effector branch outcompetes the protective abilities of the regulatory branch, causing inflammation. OneVax’s researchers seek to restore the balance between these two branches by employing antigens, drugs and cell signaling proteins, or cytokines, which specifically correct the immune response directed to the pancreas.

Studies conducted in the laboratories of the investigators in the Non-Obese Diabetic mouse model of Type I diabetes have been employed to test the efficacy of the negative vaccine particles. NOD mice are genetically susceptible and spontaneously develop diabetes; many of these genes are also involved in the development of Type I diabetes in humans. The mouse immune system has a great deal in common with that of a human; similarities include many of the cell populations that play a role in human Type I diabetes. This animal model provides a unique opportunity for OneVax to test vaccine formulations targeted to control inflammation and enhance the activity of the regulatory response. In essence, the model provides an opportunity to create an ideal therapeutic approach before moving into clinical trials in humans. Their vaccine formulas have already demonstrated efficacy in preventing diabetes in the NOD mice.

“The whole goal of OneVax is now to see if we can not only optimize some of these therapies but then get them further along in the drug pipeline,” Brusko said.

In the laboratory at the Innovation Hub, senior scientist Jamal Lewis, Ph.D, and senior laboratory technician Greg Marshall, Ph.D, are currently working on manufacturing the particles and testing their effects on the body, mechanisms of release, and toxicology. OneVax is currently three months into their one-year SBIR grant, after which they will apply for the next phase of additional funding.

“While it may be several years before this type of technology reaches the clinic,” Brusko said, “we are excited about the therapeutic potential of our approach, and we are eager to move this technology forward.”