September 11th, 2015
Engineered Macrophages Deliver GDNF to the Brain
This is one example of many new approaches to delivering therapeutic proteins into the brain. In this case the aim is to spur greater regeneration and cell resilience in order to compensate for neurodegenerative processes underlying diseases such as Parkinson's:
Researchers genetically modified white blood cells called macrophages to produce glial cell-derived neurotrophic factor, or GDNF, and deliver it to the brain. Glial cells provide support and protection for nerve cells throughout the brain and body, and GDNF can heal and stimulate the growth of damaged neurons. "Currently, there are no treatments that can halt or reverse the course of Parkinson's disease. There are only therapies to address quality of life, such as dopamine replacement. However, studies have shown that delivering neurotrophic factor to the brain not only promotes the survival of neurons but also reverses the progression of Parkinson's disease." In addition to delivering GDNF, the engineered macrophages can "teach" neurons to make the protein for themselves by delivering both the tools and the instructions needed: DNA, messenger RNA and transcription factor.Successfully delivering the treatment to the brain is the key to the success of GDNF therapy. Using immune cells avoids the body's natural defenses. The repurposed macrophages are also able to penetrate the blood-brain barrier, something most medicines cannot do. The reprogrammed cells travel to the brain and produce tiny bubbles called exosomes that contain GDNF. The cells release the exosomes, which then are able to deliver the proteins to neurons in the brain.