Breakthrough Brain Model Offers Testing Ground for Parkinson’s Treatments

As part of an international collaboration, researchers from DTU are creating a brain model that mimics the system in the brain that does not work in patients with Parkinson’s disease. The new model makes it possible to investigate the mechanisms of the disease that cause a decline in the production of a type of dopamine that coordinates movements and motor functions in the brain.

The brain model is being developed in the EU-funded OpenMIND project, where researchers from DTU and Lund University now have an early prototype ready. The model is made of small pieces of brain tissue grown from stem cells. Together, the brain cells in the tissue represent the damaged brain system seen in patients with Parkinson’s disease.

“The model is designed to mimic the nigrostriatal pathway, which is the part of the brain where dopamine controls body movements. In other words, we’re recreating the biological process that takes place inside the brain, and the model will enable us to test and develop new medicines and treatments. And this is crucial for a disease like Parkinson’s, where we can’t take a biopsy of a patient’s brain without causing significant damage,” says DTU Professor Jenny Emnéus who is contributing to the OpenMIND project, particularly with the development of the brain model.

One of the treatments that can be explored with the new brain model is cell replacement therapy, which can alleviate the tremors experienced by patients with Parkinson’s disease. During cell replacement therapy, doctors transplant stem cells into the patient’s brain, after which the cells will grow and replace the damaged cells involved in the dopamine release system. A few countries around the world have begun experimenting with this type of treatment, including Sweden, where doctors in Lund performed the first stem cell transplant on a patient with Parkinson’s disease in February 2023.

Stem cells from an inseminated egg

The human stem cells used by the researchers in the OpenMIND project come from the early stages of an artificially inseminated egg—an embryo—where the cells can develop into any of the body’s cell type. The cells are known to professionals as pluripotent stem cells. They can self-renew endlessly, which means that, in principle, the researchers can grow enough stem cells to treat every patient with Parkinson’s disease from a single inseminated egg.

It is common knowledge that light can help activate the release of dopamine, and researchers use this to their advantage when studying the mechanisms of Parkinson’s disease in the brain model. They do this using a special variant of the pluripotent stem cells that have been genetically altered to be sensitive to light. In the brain model, the light comes from ultra-thin optic cables less than 1/10 mm in size.

The optic cable in the brain model was invented separately in collaboration with Professor Stephan S. Keller and others at DTU, Lund University, and Universidad Autónoma de Madrid. In the project, the researchers exposed the optic cable’s plastic coating to high temperatures to turn the surface into coal, because this gives the cable the important ability to conduct electricity. In this way, the cable can also be used as a sensor to measure dopamine and other important chemicals involved in the brain system that is being studied.

“The experiments show that with the optic cable, we can initiate the release of dopamine from the surrounding cells and detect whether the cells are releasing dopamine at the same time,” says Jenny Emnéus.

Potential implant

Another interesting aspect of the charred surface of the optic cable is that stem cells can grow on it and develop into dopamine-producing brain cells. The cells still need to be activated by light, so the researchers have used a laser to cut small notches in the carbon surface to let light in to stimulate the release of dopamine.