CAT-7

• Cerebral aneurysms affect nearly 2-5% of the population and upon rupture can cause up to 50% mortality, and there is no simple non-invasive test for cerebral aneurysm detection.
• CAT-7 is the first simple blood test that can diagnose cerebral aneurysm formation and monitor progression through a unique risk of rupture score which no other test on the market can provide.
• Our peer-reviewed study estimates introduction of a blood test can result in 3x survival benefit in patients needing routine monitoring and ~10x survival benefit in screening of high-risk groups.
• The PInCh award would help us increase the sample size of our current study which will improve accuracy and allow us to fine tune our predictive algorithm in high-risk populations of interest.

Cerebral aneurysms affect 2-5% of the population in the United States. Currently, patients with an undiagnosed cerebral aneurysm present to their primary care physician with non-specific symptoms. Their physician manages these patients through a battery of standard protocols in search of the cause of the symptoms. These patients are then referred to neurologists who add their expertise to search for a cause, sometimes repeating or adding tests. 

After eliminating all other possible causes of a patient’s symptoms, a digital subtraction angiography (DSA) is utilized. DSA is an expensive and invasive medical imaging procedure utilizing a contrast agent (dye) that has the risk of kidney toxicity. Patients must undergo a watchful waiting period, routinely receiving imaging every 6 to 12 months until the risk of allowing the aneurysm to grow is higher than the risk of surgery. This watchful waiting period can go on for years – unfortunately, a patient's cerebral aneurysm frequently ruptures, or bursts, before diagnosis and treatment often within weeks of them noticing symptoms.

Furthermore, there are currently no recommendations for aneurysm screening for the large number of patients who are at high risk. Minority groups experience worse outcomes largely attributed to lack of access to diagnostic care, stressing the need for better access to screening modalities.

CAT-7 is a simple blood-based diagnostic test for cerebral aneurysm detection and monitoring. Testing with CAT-7 begins with collection of blood from a patient. The collected blood is then transferred onto a proprietary membrane utilizing industry standard enzyme-linked immunosorbent assay (ELISA) technology. This membrane has 7 antibody spots that correspond to the 7 biomarkers we are measuring. The membrane is imaged using an ELISA reader, which are common in most hospital laboratories and used for a variety of other blood-based tests.

The measurements for the biomarkers from the ELISA reader are then input into our algorithm. The algorithm then provides a patient’s probability of having an aneurysm and their risk of rupture metric.

Over 233 unique samples from patients with and without cerebral aneurysms were collected for our study and helped validate our technology. Our test reports accuracy of 90%, with a sensitivity of 95%, specificity of 70%, PPV 84%, NPV 90%, and p-value 0.0027. In addition, we report 90.9% accuracy (100% sensitivity and 90% specificity) in identifying inflammatory profiles at high-risk for rupture. We estimate CAT-7 can be performed at 1/100th of the cost of the current standard of care, opening the door for screening and regular monitoring.

• Adi Mittal, BS, Medical Student, University of Pittsburgh
• Kamil Nowicki, MD, PhD, Endovascular Fellow, Yale University / Yale – New Haven Hospital (UPMC graduate)
• Michael McDowell, MD, Assistant Professor, Department of Neurological Surgery, University of Pittsburgh Medical Center
• Ali Alattar, MD, MAS, Resident, Department of Neurological Surgery, University of Pittsburgh Medical Center
• Joe Garcia, MD, Resident, Department of Neurological Surgery, University of Pittsburgh Medical Center
• Priyadarshini Mamindla, MS, Hillman Cancer Center, University of Pittsburgh Medical Center
• Robert Friedlander, MD, MA, Chairman, Department of Neurological Surgery, University of Pittsburgh Medical Center
• Dan Wecht, MD, Clinical Professor, Department of Neurological Surgery, University of Pittsburgh Medical Center

Our primary approach to market is to first pursue accelerated FDA breakthrough designation and proceed through the 510(k) regulatory pathway. The studies for FDA clearance will be bolstered by PInCH funding and further supported by SBIR. Our team was invited to submit a SBIR grant application to the NSF in July 2023, which acknowledges the national impact of our innovative technology.

After clearance, we plan to partner with large diagnostic companies. The impact of this technology is confirmed by over 7 letters of support we have received for use of this product once it is commercially available and collaboration for a future multisite clinical trial. Our enthusiastic collaborators include nationally recognized sites such as Harvard / MGH hospital, Emory University, and Houston-Methodist Hospital as well as international sites in Bristol, United Kingdom.

CAT-7 offers a less expensive, noninvasive approach to diagnose CA while providing more information to the clinician to improve the outcomes of CA treatment for the patient and the impact of this technology is supported both nationally and internationally.

• Since there are gender-specific differences in cytokines, will the same set of cytokines and/or algorithm for generating an integrated output apply to male vs female patients? 
  There are dynamic differences in cytokines across both gender and age. We plan to include this important aspect of gender-specific differences in inflammation and immune system. We will optimize and develop separate algorithms for both male and female patients.
• What will be the steps physicians take once the test shows high-risk of rupture? 
  We have invested in an exhaustive, third-party customer interview study to develop a treatment protocol with physicians. To screen, CAT-7 can rapidly shunt patients with an unknown aneurysm into the treatment pathway. For surveillance, CAT-7 can be used frequently to monitor aneurysm risk of rupture and optimize treatment timing.
• How much blood does this test require? Currently this test can function with 1 mL of blood from a patient per test (less than most standard blood work).