Ingrid, DC from University of Heidelberg, is focusing on developing personalized medicine approach for a small group of people living with ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease. ALS is a severe condition in which the nerve cells that control muscle movement slowly break down. As these motor neurons are lost, everyday movements become harder, eventually leading to paralysis and a shortened lifespan.
In the group of patients Ingrid is studying, ALS is caused by specific genetic mutations – small changes in their DNA. These mutations lead to the production of a harmful protein inside motor neurons. Over time, this toxic protein contributes to the destruction of these vital cells.
Ingrids goal is to intervene before the toxic protein is made. To do that, she focuses on an intermediate step between DNA and protein called RNA. RNA is like a temporary copy of DNA – a blueprint the cell uses to build proteins. Unlike DNA, it’s safer to target because it’s not the original “master copy”. At the same time, it allows her to be very precise.
To change how this RNA blueprint is built, Ingrid uses molecules called antisense oligonucleotides (ASOs). These tiny, custom-designed pieces of genetic material bind to the RNA and change how the blueprint is processed in the cell. This way, she aims to stop the production of the toxic protein and encourages the cell to make the healthy version instead.
Before any treatment can move to the clinic, Ingrid and her colleagues at the University of Heidelberg need to ensure it is both effective and safe. Forst, she tests the ASOs in cells derived from patients, examining how they affect RNA and protein levels. If the results are promising, she will then assess safety in more complex systems, including living animals. For more information on how safety testing works, you can read about the projects of Laura (DC6) and Ràul (DC7).