Description:
Creatine Transporter Deficiency (CTD) is a severe x-linked linked mental retardation disorder. It is caused by mutations in the creatine transporter gene (SLC68A). Mutations in this gene result in an inability to move creatine across the blood brain barrier. This inability to transport creatine across the blood brain barrier results in a severe deficit of creatine in the CNS and this lack impacts energy homeostasis. Currently, diagnostic biomarkers rely on CTD diagnosis. While there are only a few hundred patients who have been accurately diagnosed with this disorder it is estimated that there are upwards of 40,000-50,000 individuals that are now labeled with x-linked mental retardation or autism. Clinical research of potential therapeutics will rely on the availability of a pool of patients, as well as attempts to better understand the extent and progression of the disease through natural history studies. This initiative seeks to develop a biomarker for use in Creatine Transporter Defect disease. This biomarker would correlate to the nature of CTD and allow its use to identify patients suitable for inclusion in clinical trials. There is the potential that this biomarker could find utility as a diagnostic after validation.
Main requirements
The outcome of this contract is expected to be a biomarker to monitor the effects of creatine depletion in the CNS. This biomarker would be most useful if it could be tracked in blood or urine but cerebral spinal fluid markers would also be acceptable. This biomarker would have a large impact on patients if banked tissue and blood samples could be examined as well. This biomarker must show a difference between normal volunteer, diagnosed CTD patients and the difference from other autistic or cognitively impaired patients whose symptoms are not related to creatine transporter deficiency. This assay should be able to be performed in reasonable throughput.
Deliverables Phase 1
A biomarker assay that meets the requirements listed above and also meets the following:
• Develop a working assay
• Characterize the variability, reproducibility and accuracy of the detection
• Demonstrate the utility of the assay by characterizing differences between normal volunteer, diagnosed CTD patients and the difference from other autistic or cognitively impaired patients whose symptoms are not related to creatine transporter deficiency
• Deliver the SOP of the working test to NCATS
Deliverables Phase 2
• Demonstrate clinical utility by testing a large number of patient samples or banked tissue or plasma samples
• Establish a relationship with companies developing therapeutics for the creatine transporter deficiency patients
• Deliver final SOP to NCATS for evaluation
