NEW YORK – A startup out of the University of Helsinki is developing a diagnostic tool to analyze how lipids are processed in the body, betting that the test can guide treatment decisions for patients who are at risk of or have cardiovascular disease.
Moncyte Health, which is also based in Helsinki, launched last year with €1 million ($1 million) in seed capital to establish its go-to-market strategy for a diagnostic test it is developing to support clinicians in personalizing medication plans. This year, it is working to validate its test with the hopes of eventually getting it to the clinical market.
"We look at the cellular processes underlying disease progression," Simon Pfisterer, cofounder and CSO at Moncyte and a research group leader in the anatomy department at the University of Helsinki, said of the company's mission. "That opens up new ways for precision medicine in the cardiovascular space."
Moncyte's first target is high cholesterol, a major risk factor for cardiovascular disease, which can lead to heart attacks, strokes, and other medical problems. High cholesterol occurs when there are high levels of fat in a patient's blood vessels, making it difficult for blood to flow through arteries. The condition can be inherited, but is often caused by lifestyle factors, such as diets high in saturated and trans fats and a lack of physical activity. After onset of heart disease, even with lifestyle modifications, patients might have residual risk that requires medication.
However, even with lipid-lowering drugs many patients don't achieve target cholesterol levels and could benefit from tailored treatment plans, Pfisterer said. In this arena, "there's very little precision medicine," he said. "It's mostly trial and error by doctors."
There are numerous lipid-lowering medications available on the market such as statins, PCSK9 inhibitors, fibrates, or omega-3 fatty acids that target different types of substances in the body and may aim to decrease a patient's low-density lipoprotein (LDL) cholesterol or triglyceride levels. Some of these drugs also aim to increase high-density lipoprotein (HDL) cholesterol.
These drugs work in different ways. For example, PCSK9 inhibitors are designed to block the degradation of the low-density lipoprotein receptor (LDLR), while statins inhibit the HMG-CoA reductase enzyme to deplete production of cholesterol and increase LDLR expression, according to a preprint paper by Pfisterer and colleagues at the University of Helsinki.
On the horizon, there are even more drugs being tested in late-stage clinical development that target other lipids, such as those targeting lipoprotein(a), a type of LDL cholesterol, and triglycerides, a different type of lipid found in the bloodstream, both of which are also risk factors for cardiovascular disease.
Moncyte's blood test is based on cell biology research conducted at the University of Helsinki to better understand how cholesterol is transported and processed in cells and how this affects cardiovascular disease progression. Since these pathways may also influence response to lipid-lowering drugs, Moncyte is betting the insights can inform prescribing decisions.
Unlike other diagnostic tests, such as blood tests that measure cholesterol concentration, Moncyte's tool doesn't quantify biomarkers in the blood. Instead, the test is designed to quantify biological differences in cellular processes that affect lipids by analyzing how white blood cells such as monocytes take in lipids and store fat. Each test involves analyzing thousands of white blood cells derived from a patient's blood sample using multiplex high-content microscopy.
These cells play a critical role in inflammation and in the formation of atherosclerotic plaque, processes that are related to high cholesterol and influence the effectiveness of lipid-lowering drugs. "We focus on monocytes that are key to atherosclerosis, and we [assess] an individual response to lipid particles," said Tamara Alagirova, Moncyte cofounder and CEO.
The test results are presented as scores that incorporate measures of lipid mobilization and LDL uptake. For example, to assess uptake of LDL, Moncyte measures the average internalized and surface-bound LDL particles in the white blood cells as well as the number of LDL-filled organelles, representing only internalized LDL, in both lipid-rich and lipid-poor conditions.
In the 2023 preprint, Pfisterer and colleagues demonstrated that biological variation in cellular lipid trafficking pathways, as characterized by these scores, were associated with clinical outcomes in patients taking statins. They described this as one use-case for the diagnostic.
Pfisterer and colleagues used the technology that would become Moncyte's test to characterize differences in cellular lipid trafficking in white blood cells from 400 participants in the FINRISK 2012 Study, a population study in Finland. They found that most patients who had lower cellular lipid trafficking scores did not reach LDL-C target levels if they were only on statin treatment. Among patients taking high-intensity statin therapy, those with lower cellular lipid trafficking scores tended to have residual cardiovascular risk, with higher concentrations of pro-atherogenic lipoproteins and a higher likelihood of experiencing a heart attack or stroke when compared with other participants receiving the same treatment.
Meanwhile, patients with higher lipid trafficking scores achieved their LDL-C goals while on high-intensity statin monotherapy, according to the study authors.
If sold to physicians, Moncyte could deliver such scores in a report, alongside medication recommendations.
"These cellular responses really link with what people achieve on, for example, high-intensity statin medication," Pfisterer said. "That gives us the indication that we can use this technology to pinpoint who would need combination therapy when a statin medication is not enough."
The company is already using the test in research partnerships with pharmaceutical companies and other investigators. It recently became a partner in a four-year research project funded by Horizon Europe, called FH-EARLY. Researchers in this project are studying new strategies for earlier diagnosis and care management for familial hypercholesterolemia, an inherited disorder that causes high cholesterol, and are using Moncyte's technology to try to identify pathways and cellular mechanisms that contribute to disease progression.
Within clinical trials, Alagirova said Moncyte's test also could be used by drugmakers to identify new drug targets or the patients most likely to respond to drugs they're testing, as well as to help them to better understand how lipid-lowering drugs in development may influence cellular processes that contribute to cardiovascular risk.
Alagirova declined to disclose the names of pharmaceutical companies that Moncyte is working with.