Targets and Methods of Diagnosing, Monitoring & Treating Frontotemporal Dementia

Description

Diverse pathologies, especially related to early protein misfolding and aggregation, are observed in different neurodegenerative diseases. Some protein variants result in different proteinopathies that vary from patient to patient, highlighting a need for personalized diagnostic tests to enable accurate diagnoses.

Frontotemporal dementia (FTD) refers to a group of uncommon brain disorders caused by progressive nerve cell loss in the frontal and temporal lobes of the brain. FTD is a common cause of dementia in younger patients (midlife or earlier), however, because of the issues with diagnosing FTD, precise estimates of its prevalence and incidence are unknown.

Researchers at Arizona State University have developed a panel of novel single-chain variable fragments (scFvs) that specifically recognize protein variant biomarkers associated with frontotemporal dementia. These reagents can be used for diagnosing, monitoring and may even help in the development of potential therapeutics for preventing or treating FTD. Sera from 24 FTD cases were analyzed and the scFVs were able to detect all of them. Additionally, novel targets were identified that could be used in developing FTD treatments.

This panel system enables a more personalized approach for diagnosing and monitoring FTD patients and centers on a wider range of targets which may help create effective treatment strategies.

Potential Applications

•       Early stage diagnosis of FTD patients

•       Development of therapeutics for treating FTD

o       Novel targets not previously associated with FTD

o       The scFvs could be conjugated to therapeutics and used for targeted delivery

o       May also be used to prevent development of FTD

o       May also be used to monitor the efficacy of therapeutic agents for FTD

•       Monitoring the pathology of FTD

•       In vivo imaging of target morphologies of molecules associated with FTD

Benefits and Advantages

•       Diverse binding patterns observed between TFD-TDP and FTD-Tau cases

•       More personalized approach for diagnosing FTD patients

•       These scFvs can serve as excellent indicators of progressing pathology

•       Flexible assay format – can use blood, CSF, and potentially other biological fluids

•       Can distinguish FTD from other neurodegenerative diseases as well as different FTD groups (i.e. FTD-TDP vs FTD-Tau)

•       ROC above 0.9 and sensitivity and specificity above 90%

For more information about the inventor(s) and their research, please see

Dr. Sierk's departmental webpage