A researcher at Humboldt University of Berlin has successfully developed a biochemical test suitable for the early diagnosis of the rare genetic disorder ASMD. Since 2012, Prof. Christoph Arenz has been a professor of Organic and Bioorganic Chemistry at the university and is an internationally recognized expert in the field of sphingolipids, particularly in acidic sphingomyelinase.
ASMD (Acid Sphingomyelinase Deficiency) — also known as Niemann-Pick disease types A/B — is a rare, inherited, life-threatening disorder characterized by a deficiency of the ASM enzyme. The condition leads to multiple organ failure. Patients with the milder form of the disease can reach adulthood. A significant challenge is that ASMD is very difficult to diagnose, partly because its symptoms closely resemble those of approximately 50 other rare genetic disorders. As a result, diagnosis is often delayed. Treatment for these various genetic disorders, if available, differs in each case. There are frequent reports of patients being treated for years with incorrect medications due to a misdiagnosis of their original condition.
Fig.: Principle of the chemical probe for detecting ASM deficiency (ASMD).
Top: Chemical structure of the fluorescence probe.
Bottom: Application of the probe in cells without ASM activity (blue) and with ASM activity (red). The fluorescence of 10,000 cultured cells is shown. A similar experiment could be conducted with (blood) cells from patients.
The probe molecule method developed by Prof. Arenz and his team, including Christian Kappe and Dr. Maria Russi, can be considered groundbreaking. This method enables the activity of the enzyme "acid sphingomyelinase" (ASM) to be detected without expert knowledge or extensive equipment and even within living cells. The probe molecule allows for the rapid and straightforward determination of ASM activity in fluids or cultured cell lines. The next step involves testing this now routinely used biochemical method on blood and urine samples from patients to validate its application in clinical diagnostics. There is justified hope that this new method will make it easier to detect the genetic disorder earlier, for example, as part of newborn screening, enabling patients to receive appropriate treatment at an early stage. The timing for this initiative is excellent, as the first treatment method for ASMD received clinical approval in numerous countries just last year.
Translating innovative research results into economic applications requires thorough validation and an assessment of a project's potential for industry transfer. This process is often underestimated and requires funding, which is frequently lacking in research. Many researchers fail to bridge the "Valley of Death"—the gap between innovative research ideas or technologies and their funded further development. This is where the "ProValid" program comes in, aiming to close this gap. The validation funding concept was developed by the transfer units of Berlin's universities, tested and evaluated in a pilot project by the Senate Department for Economics, Energy, and Public Enterprises through Humboldt-Innovation GmbH, and subsequently rolled out.
Regarding the now-funded project, the "ProValid" program plans to scale up the probe molecule and evaluate the conditions for its application. This includes determining what biological material is needed and assessing whether equipment available in clinics can be used for the procedure. Additionally, the patentability of the method will be explored. During the validation phase, the team collaborates with clinical partners. If validation is successful, the next steps will include a larger-scale clinical study, promoting the ASM test, and deciding how the research results will be commercially utilized.