Heart failure, Alzheimer’s, cancer: microRNA in medicine
Published: Monday, Oct 7th 2024, 15:40
Updated At: Tuesday, Oct 8th 2024, 01:59
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Cancer, autoimmune diseases, heart problems: The regulation of genes plays a key role in many diseases. It has been known since the 1960s that the so-called messenger RNA (mRNA) carries the blueprint for the production of proteins in cells. In contrast, non-coding RNAs - i.e. without such information - were long regarded as genetic waste. This year's Nobel Prize winners Victor Ambros and Gary Ruvkun have disproved this for some of them, the microRNAs.
The microRNAs (miRNA) they discovered have been shaping the development of organisms for hundreds of millions of years - and therefore also human health. The molecules are formed by body cells and are intended to ensure that certain proteins are produced in the right amount at the right time in the right body tissue.
Involved in many diseases
However, the molecules can also be involved in disease processes, such as tumors, heart failure, congenital hearing loss or visual impairment. Mutations in one of the proteins required for miRNAs cause DICER1 syndrome, for example. This rare disease leads to tumors in various organs. Conversely, miRNAs could be used to combat diseases - either by blocking miRNAs or by using artificially produced molecules in a targeted manner.
Around 30 years after Ambros and Ruvkun's discovery of the nematode, there are still no approved medical procedures. However, a number of such uses are now on the threshold of medical application: studies on humans are investigating whether microRNAs can be used to diagnose diseases or for therapy.
Take heart failure, for example: in heart failure, the heart is too weak to pump blood around the body. According to the Heart Foundation, more than 40,000 people in Germany die from this every year. A drug developed in Hanover, CDR132L, binds to microRNA-132, which contributes to the scarring of the heart muscle - it is intended to slow down or even halt the progression of heart failure.
Possible therapies
"Our team was first able to show in Nature in 2008 that microRNA can be used therapeutically to treat heart failure in mice," explained Thomas Thum from Hannover Medical School (MHH). "In the meantime, we have conducted the world's largest phase 2 study with almost 300 patients after myocardial infarction and a microRNA approach." Thum, founder of the start-up Cardior, expects "a new generation of miRNA-based drugs" that could be used to treat many diseases. The approach is also being tested against kidney and lung fibrosis.
Take cancer, for example: "miRNA plays a very important role in tumors," said Sven Diederichs from the German Consortium for Translational Cancer Research and the University of Freiburg. miRNA can suppress tumor-inhibiting genes, and its loss can activate cancer genes.
As the molecules are very characteristic of certain tissue types, they can also be used in diagnostics, as Diederichs explained. In the case of pancreatic and lung cancer, this could not only help to detect tumors at an early stage, but also to track any progress in therapy. Therapies with miRNAs are currently being tested - not only on pancreatic tumors, but also on lung cancer and brain tumors.
Early detection of Alzheimer's
Take Alzheimer's, for example: miRNAs can improve the early detection of the most common form of dementia, as an international research team writes in the journal "Alzheimer's & Dementia" following a study involving 800 people. Not only do we need therapies to treat Alzheimer's, but also new approaches to detect the disease before symptoms such as memory impairment occur, said André Fischer from Göttingen University Hospital. "We have discovered that this is possible by measuring microRNAs in the blood."
The method is not yet ready for clinical routine. They are working on a simple blood test that detects several miRNAs using a drop of blood from the finger. Fischer believes that this test could be on the market in a few years. It could complement complex procedures such as the analysis of spinal fluid and brain scans.
However, to date there are no approved drugs based on miRNAs. Considering that these RNA variants have only been known in humans for two decades, research is already quite advanced, said Diederichs. An economic development also suggests that the approach has medical potential: it was only in May that the Danish pharmaceutical company Novo Nordisk - known for its Wegovy delivery syringe - acquired the start-up Cardior, founded by Thum, for around one billion euros.
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