Scientists are inventing a small model miming the part of the brain affected by Parkinson’s disease. The model will improve our understanding of the disease and pave the way for testing new treatments. The technology could lead to the development of an implant.
The researchers have developed these probes that can potentially be implanted in the brain. At the tips, stem cells can grow, which can release dopamine. Photo credit: Thomas Steen Møller / DTU
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 comprises 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, the part of the brain where dopamine controls body movements. In other words, we’re recreating the biological process 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 developing the brain model.
On the left is a large model of the structure included in the brain model. On the right, the structure is the correct size and is charred. It is on this structure in the brain model that the stem cells grow. Photo credit: Thomas Steen Møller/DTU
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.
This solution opens up the possibility of developing technology for an implant that could be implanted in the brain of a patient with Parkinson’s disease. The researchers have now developed the first prototype, and it is ready for animal testing.
“The implant could potentially enable us to treat Parkinson’s in the exact part of the brain that’s affected. Today, patients are treated with oral medications. The medicine thus not only reaches the affected area but the entire brain, causing a number of unwanted side effects,” says Jenny Emnéus.
The DTU researchers are working together with researchers from Italy and Norway to develop a remote control that patients can use once they have had their implant inserted. The remote control needs to reach the implant and activate the light, thereby stimulating the release of dopamine while also measuring how much dopamine is released, when patients experience symptoms.
If the researchers are successful in developing the system, the questions still remains for how patients will manage their own doses.
“We imagine that a doctor will prescribe the dopamine doses, or that based on the patient’s symptoms, a doctor will prescribe the interval of the dopamine doses, so that patients do not end up putting a strain on their brain,” says Jenny Emnéus.
New treatment 10 years down the road
The OpenMIND research project has secured funding until 2025 and is expected to lead to the development of a test platform for other neurodegenerative diseases. Among other things, the test platform is to be made available to private companies for testing new medicines and treatments for diseases.
Source: DTU