Regeneration of neurons in vivo
Modern treatment of ischemic stroke is aimed at restoring blood flow and neuroprotection, usually with a short time interval of several hours. However, many stroke patients cannot get to the hospital within a few hours after the onset of the stroke and suffer from the death of a large number of neurons and loss of brain function. Thus, the restoration of functional neurons after a stroke is the key to restoring brain function.
A team led by Professor Gong Chen from Jinan University, China, conducted a study on non-human primates that demonstrated successful regeneration of neurons in vivo from glial brain cells to recover after a stroke.
Earlier, Professor Chen's group published a series of papers demonstrating that overexpression of the neural transcription factor Neurogenic differentiation 1 (NeuroD1) can directly transform glial cells into neurons in the brain of mice. However, most clinical studies of stroke in recent decades have failed, perhaps because successful rodent trials are not suitable for transfer to a clinic. Since the transformation of glia into neurons in vivo is an innovative technology, the authors decided to continue work on the validation of this new technology in non-human primates.
The researchers induced ischemic stroke in rhesus monkeys aged 9 to 21 years to simulate the typical course of stroke in the elderly. Using the astrocytic promoter GFAP (glial fibrillar acid protein) to control the expression of the neural transcription factor NeuroD1, Chen's group successfully demonstrated that reactive astrocytes that appeared in response to ischemia in the brain of monkeys can effectively turn into neurons. The density of neurons in the brain areas treated with NeuroD1 was consistently higher than in those that were not treated with NeuroD1.
Neurons formed from astrocytes in the brain of a rhesus macaque after a stroke.
What was unexpected for the researchers was that the class of stroke-sensitive interneurons was protected after the introduction of NeuroD1, which is accompanied by a significant decrease in inflammation. This result is important because the conversion of astrocytes into neurons in vivo not only restores brain tissue, but also protects damaged cells from secondary damage, preventing further death of neurons. The processes of neuroregeneration and neuroprotection can together have a huge impact on the recovery of the brain.
To deliver the NeuroD1 transgene, adeno-associated vectors (AAV) were used by direct intracranial injection into the ischemic region of the primate brain. Unlike classical gene therapy aimed at correcting gene mutations, this technique generates new neurons, which makes it a kind of cell therapy mediated by gene therapy.
Article L.-J.Ge et al. In vivo Neuroregeneration to Treat Ischemic Stroke Through NeuroD1 AAV-Based Gene Therapy in Adult Non-human Primates is published in the journal Frontiers in Cell and Developmental Biology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: First non-human primate study showing promise of gene therapy for stroke repair.