We are delighted to have access to some great scientists working in the field of CDKL5 Research across the world. Associate Professor Alysson Muotri, from University of California San Diego, School of Medicine, has written this perspective on modelling CDKL5 Disorder using human brain cells, this is the field he is currently working on as well as his extensive research on Autism. What is great about this article is that he has written with both families and professionals alike in mind in a hope to ensure that it is easily understood.
The Muotri lab perspective: modelling CDKL5 Disorder using human brain cells
The unavailability of live human brain cells for research has blocked progress toward understanding mechanisms behind neurological disorders. Although animal models are a great resource for studying neural development and neural systems, the majority of these models only partially recapitulate human diseases. For example, an important feature of CDKL5 syndrome is the occurrence of early-onset seizures, most often intractable, which is not mimicked by the current animal model.
Luckily, novel techniques in stem cell biology allow us to convert peripheral cell types, such skin or dental pulp, into live functional brain cells. Having live brain cells in the lab allow researchers to explore the causes of the disease and to find potential drug candidates. Thus, we have generated “mini-brains” in-a-dish from individuals with different CDKL5 mutations. Our data shows that neurons carrying CDKL5 mutations do not produce certain neurotransmitters in the right amount, necessary for proper connection and neuronal communication. Thus, we are now currently testing molecules that could compensate such deficiency. We believe that by stimulating or inhibiting specific neurotransmitters we will be able to control the atypical electric behaviour of CDKL5 mutant neurons. Finally, we will compare our mini-brain data with the EEG records of actual patients’ brains. This approach will accelerate the identification of therapeutic drugs that could efficiently reverse and/or control the abnormal behaviour of neurons and, consequently, improving CDKL5 patients’ quality of life.
It is quite amazing that we are now able to perform such experiments with live human neurons in the lab. A couple years ago, this would be something neuroscientists could only dream about it. It was science fiction and now is a reality.