Grant: Project Grant

Neurological conditions such as Alzheimer's Disease and Parkinson's Disease affect people with age, but there are also certain genetic mutations that cause childhood-onset neuronal diseases. We recently identified a new disease that is caused by a mutation in a gene called the choline transporter-like 1 (the gene symbol is SLC44A1). We found 3 families whose children were affected by this condition and who had serious cognitive impairments. Our research aims to find out how this mutation leads to the neurological disorder and to test potential therapeutic strategies for this disease. Our research will focus on human patients, cells from these human patients and finally a new genetic mouse model that will all lead to a better understanding of this disease. First, we will look for important markers of the disease in the identified human patients (other than the gene mutation) to hopefully tell us more about screening, including specialized blood tests and brain scans. Secondly, we will use skin cells from affected patients and culture these cells in a way that causes them to revert to a special type of stem cell. This new stem cell will have the ability to become any other cell type if we give it the right ingredients. With this important cell model, we can produce 3 types of important cells that are found in the brain: neurons (they do the thinking), glial cells (these are like helper cells for neurons) and cells called microglia (these are a special immune cell in the brain). With these three cell types from patients affected, we will be able to conduct experiments that will try to understand disease mechanisms. Finally, we will use a genetic mouse model that also carries a mutation in the same gene as the human patients to test the importance of each cell type and a potential drug as a therapy. Our research goal is to understand and develop patient-oriented treatments for this newly discovered childhood-onset neurological condition.