Baker spinoff company to test stroke diagnostic in hospital trial
New diagnostic technology evolved from basic research on sperm biology
When Dr. Alex Travis began investigating how sperm cells swim more than a decade ago, he had no idea the research would lead to a new way to diagnose stroke and other diseases. Now, Travis and Dr. Roy Cohen have co-founded a company, TETDiagnostics, to transform what they learned from sperm into a bio-inspired diagnostic technology. Using enzymes immobilized onto nanoparticles, they can detect biomarkers released through a brain injury into the blood. These "tethered" enzymes mimic the way that sperm cells anchor the energy-producing enzymes that power their tails. Ultimately, the researchers plan to develop this tethered enzyme technology (TET) into a range of point-of-care diagnostic tests that can be performed anywhere using a handheld device.
Their Initial research has shown that the enzyme-based test effectively diagnoses stroke and concussions, but now with new funding, Travis and Cohen will undertake a clinical study with 200 patients. The Centers for Advanced Technology (CATs) at the Cornell Institute for Biotechnology have awarded Cohen a one-year grant for $75,000 for the trial, which will be hosted by the Guthrie Robert Packer Hospital Primary Stroke Center in Sayre, Pennsylvania. If the test successfully diagnoses stroke patients in a hospital setting, Cohen and Travis hope to take the next steps to make their test available to patients. The current clinical trial with Guthrie was also made possible with support received by the Albert C. Bostwick Foundation. The foundation has been a long-time supporter of the Baker Institute for Animal Health, and an early champion of the Institute’s biotechnology initiatives. Many family members of the Bostwick Foundation have had close ties to the Institute over the years, including current Advisory Council member Michael Raeburn Parker, who is specifically interested in this project’s focus on veterinary and biomedical clinical applications.
Stroke: When seconds count
Cohen and Travis chose stroke as one of the first applications for their diagnostic technology because the faster a blood clot in the brain — called an ischemic stroke — can be diagnosed and treated, the less brain damage the patient will incur. "The assay takes advantage of the fact that enzymes are super efficient and work very fast to generate a readout signal, so the results are available in just a few minutes," said Cohen, a research assistant professor at the Baker Institute.
Patients with possible stroke symptoms typically undergo a neurological exam followed by a CT scan to rule out a brain hemorrhage. If an ischemic stroke is diagnosed within four and a half hours of symptom onset, patients can receive the clot-dissolving medicine tPA. But currently, about 70 to 85 percent of patients miss that four-and-a-half-hour window, in part, because diagnosis takes too long. Also, in people with symptoms that mimic a stroke, such as a seizure, migraine headache or low blood sugar, about 10 percent receive tPA unnecessarily, putting them at risk of serious bleeding complications.
Cohen and Travis propose that if stroke patients could be rapidly identified with TETDiagnostics' blood test upon arrival at the hospital, then more patients could receive a CT scan and tPA treatment within the critical window. Also, people with stroke mimics could be weeded out, saving them from unnecessary and potentially dangerous tPA treatment, which costs about $6,000 to administer.
The company has already performed a small pilot study involving 50 patients who received the TET diagnostic test along with their evaluation for stroke at the Guthrie/Robert Packer Hospital. "After doing all the analysis, we were very excited with the results," said Cohen. "We found that we have a very high specificity and sensitivity for brain injuries. After talking with Guthrie, they wanted to expand this study."
The Donald Guthrie Foundation, an independent organization that oversees research activities at Guthrie, is playing a major role by coordinating the trial. "The talented physician-scientists at Guthrie/Robert Packer Hospital will be providing the valuable patient populations and translating research ideas into clinical applications," said Dr. Burt Cagir, professor of Surgery, director, General Surgery Residency and executive director of the Donald Guthrie Foundation of Research and Education.
Cagir is also interested in applying the diagnostic test in patients with traumatic brain injury (TBI) as a final part of the study. "Some TBI patients are so unstable that they cannot leave the ICU to undergo CT scans, leading to delayed diagnosis and therapy," Cagir said. If the diagnostic test successfully indicates the extent of the brain injury, then patients could receive medication earlier, before a CT scan. "If we get similar sensitivity and specificity for TBI, we will be initiating a multicenter TBI study utilizing the technology," he said.
TETDiagnostics will produce hundreds of test kits for the new trial through the CAT funding, demonstrating that they can successfully scale up production.
Next, the company will seek approval from the Food and Drug Administration (FDA) for their test and industry investment to further develop the technology. They are already working with partners to develop a handheld reader to give results for a cartridge-based version of the test.
Inspired by sperm
The tethered enzyme technology grew out of Travis' research at the Baker Institute into the basic biology of sperm. This work has already grown into a commercially available male fertility test and contributed to the first puppies born by in vitro fertilization.
“One of the most fun things about science is that you never quite know which direction things will go,” said Travis, professor of Reproductive Biology, director of the Cornell University Master of Public Health Program and chair of the department of Public & Ecosystem Health.
Cells use a 10-step reaction to break down glucose to yield energy. In most cells, the enzymes involved are free-floating, but in sperm, they are anchored to the internal skeleton in the tail. Travis' lab copied this design and found they could add functions to nanoparticles by attaching different enzymes. The groups of the immobilized enzymes work even more efficiently than free-floating ones.
Initially, Travis envisioned that a similar system of tethered enzymes could power nanobots that travel through the bloodstream, consuming glucose and dispensing drugs at specific sites, such as tumors. "That was a brilliant idea," Cohen said, "but it was 20 years ahead of its time."
Travis and Cohen considered other applications and settled on rapid, point-of-care diagnostic tests. Similar diagnostics, such as rapid Covid-19 tests and pregnancy tests, use antibodies, which are slower and less specific than enzymes, and give only yes-or-no results. In contrast, enzymes are "tiny biomachines" that grab onto disease biomarkers, change them and release them, giving off photons of light in the process. A lab instrument or handheld reader can detect the emitted light to quantify how much biomarker is in the sample.
Ultimately, TETDiagnostics plans to develop a range of tests for use in clinics, at home, in schools, or even on the battlefield. Future applications include tests for liver injury and Covid-19. These same tests developed for humans can also be used in veterinary clinics, to make quick and affordable diagnoses in animals.
Besides proteins, tethered enzymes can also detect ions, metabolites, toxins and even nucleic acids such as microRNAs. "Once we worked out how to attach the enzymes, there was an explosion of what we could do," Cohen said. "There are so many disease biomarkers we can detect."
Written by Patricia Waldron
See article published in Cornell Chronicle.