Program of Research
Dr. Jeffrey Neul is a professor and neurologist at Vanderbilt University Medical Center. He orignally began his research with Dr. Huda Zoghbi who identified the gene for Rett Syndrome. He runs several clinical trials on children with Rett Syndrome specifically at the Blue Bird Circle Rett Center. Prior to his work at Vanderbilt, he worked at Baylor where he began research on animal models. He also revised the criteria for the diagnosis of Rett Syndrome in the Annals of Neurology. His overall research goal is to develop animal therapies for the specific phenotypes included in the disease progression which woud ultimately translate into human therapies that increase quality of life and longevity. Having began his specific and targeted research plan a little over a decade ago, I believe Dr. Neul is just getting started.
Articles:
Neul, J.L.,Fang, P., Barrish, J., Lane,J., Caeg, E.B., Smith, E.O., Zoghbi, H., Percy, A., Glaze, D.G., (2008). Specific mutations in Methyl-CpG-Binding Protein 2 confer different severity in Rett syndrome. Neurology, 7(16).
While there are many different mutation types regarding the MECP2 gene, some mutations are more severe and therefore cause a more severe progression and phenotypic display of Rett Syndrome. This study shows that there is sufficient cause for MECP2 in its different forms to lead to different and more advanced forms of Rett.
Samaco, R., Mandel-Brehm, C., Chao, H., Ward, C., Fyffe-Maricich, S., Ren, J., Hyland, K., Thaller, C., Maricich, S., Humphreys,P., Greer,J., Percy,A., Glaze, D., Zoghbi, H., Neul, J. (2009). Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities. PNAS, 106 (51), pgs 21966-21971.
This article shows that MECP2 gene protein is necessary for neuronal function and behavior. Without it, behavioral disorders and neuronal misifirng occurs. After establishing a clear data set from clinical trial data of the amount of aminergic metabolites present in experiemntal and control groups, mouse models were employed to further investigate this concept. The severity of the disease is positively correlated to the decreased amount of amingeric metabolites for synthesis reactions. Aminergic transmitter synthesis is ultimately dependany upon the presence of the mecp2 gene and therefore this gene is necessary to the longevity of the process.
Cuddapah, V., Pillai, R., Shekar, K., Lane, J., Motil, K., Skinner, S., Tarquinio, D., Glaze, D., McGwin, G., Kaufmann, W., Percy, A., Neul, J., Olsen, M. (2014). Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. Journal of Medical Genetics, 51(3), pgs. 152-158.
This was an entirely human based clinical study that surveyed the mutations of the MECP2 gene and the phenotypic manifestations of the disease over time. It was the largest study to date to be conducted with both typical and atypical RS patients. Deletion, insertion, and splice site mutations were the originators for the most severe RS cases while point mutations caused higher funtioning RS in most cases. This provides anticipatory knowledge for doctors, therapists, and family members to provide better intervention and treatment. No matter the intital severity, the disease does worsen with age in every case.