Unlike mere genetic waste, microRNA holds significant potential in the medical field.
For Centuries Upon Centuries, microRNAs Have Managed Human Health. They Can Lead to Suffering, Yet Aid in Relieving or Even Overcoming It. Various Methods Could've Seemed Impossible Without This Year's Nobel Prize Winners' Discoveries.
Ailments like cancer, autoimmune disorders, and heart problems often involve gene regulation's importance. The 1960s saw the realization that messenger RNA (mRNA) serves as a cell's protein production blueprint. However, non-coding RNAs, those lacking such data, were long dismissed as genetic waste. This year's Nobel laureates, Victor Ambros and Gary Ruvkun, altered this perception, focusing on microRNAs (miRNAs).
The miRNAs these researchers discovered have been shaping organisms' development – and consequently human health – for hundreds of millions of years. These molecules emerge from body cells, ensuring that specific proteins are produced at the appropriate time, in the correct body tissue, and in the right amount.
Regrettably, these molecules also contribute to disease processes, such as tumors, heart failure, hereditary hearing loss, or visual impairments. Genetic mutations influencing one of the proteins needed for miRNAs can result in DICER1 syndrome, a rare disorder causing tumors in various organs. On the bright side, miRNAs may assist in combating diseases – either by inhibiting them or by employing artificially crafted molecules specifically.
Halting Heart Failure?
Approximately thirty years after their discovery in the roundworm, no approved medical treatments exist; however, uses for these miRNAs are now on the verge of medical introduction: Human studies are now evaluating whether miRNAs may serve for disease diagnosis or treatment.
For instance, heart failure takes the life of more than 40,000 Germans annually. A Hannover-developed drug, CDR132L, aims to combat heart failure by targeting microRNA-132, which contributes to heart muscle scarring; this could potentially slow or even halt heart failure's progression.
"Our team was the first to show in 2008, in 'Nature', that microRNA can be used therapeutically against heart failure in mice," stated Hannover Medical School's Thomas Thum. Since then, Thum, creator of startup Cardior, anticipates a new wave of miRNA-based medications that could combat various illnesses. This approach is also being examined for kidney and lung fibrosis.
Identifying Alzheimer's Earlier in a Drop of Blood
In cancer's case: "miRNA is highly significant in tumors," explained Sven Diederichs of the German Translational Cancer Research Consortium and the University of Freiburg. miRNA can suppress tumor-suppressing genes, its absence can stimulate cancer genes.
As molecules are distinct for specific tissue types, they can also be used for diagnosis, as Diederichs noted. In pancreatic and lung cancer, this method could not only help detect tumors early, but also track potential therapeutic changes. Therapeutic methods using miRNAs are currently being explored – not only in pancreatic cancer, but also in lung cancer and brain cancer.
For example, in Alzheimer's: miRNAs may enhance earlier detection of the most common form of dementia, according to an international research team publishing in the "Alzheimer's & Dementia" journal. André Fischer from Göttingen University Hospital stated, "We do not only require therapies to treat Alzheimer's, but also novel strategies to identify the disease before symptoms like memory loss appear." Fischer confirmed, "We've discovered that this is possible through the measurement of microRNAs in the blood."
This procedure is not yet ready for routine clinical use. The creators are developing a simple blood test detecting multiple miRNAs from a single drop of blood. According to Fischer, this test might enter the market within a few years. It could supplement more complex methods such as analyzing cerebrospinal fluid and brain scans.
Nevertheless, no miRNA-based approved medications exist yet. Given that humans have known these RNA variants for only two decades, our research's progress is significant, Diederichs noted. The fact that this approach has medical potential is also indicated by an economic development: In May, the Danish pharmaceutical company Novo Nordisk, renowned for the weight loss injection Wegovy, purchased Thum's startup Cardior, valued at about one billion euros.
The Nobel Prize in Physiology or Medicine was awarded to Victor Ambros and Gary Ruvkun in 2022, recognizing their groundbreaking work on microRNAs and their role in gene regulation. This discovery has opened up new possibilities for combating diseases, including heart failure and Alzheimer's, by harnessing the power of these molecules.
In the case of Alzheimer's, research has shown that the measurement of specific microRNAs in a drop of blood could aid in early detection of the disease, potentially leading to the development of a simple and non-invasive diagnostic test in the near future.
