Biomarker Optimization for Progranulin Trials (The BOPT Study)

Investigator: Adam Boxer, MD, PhD
Sponsor: Alzheimer Drug Discovery Foundation

Location(s): United States


Frontotemporal dementia (FTD) is a common cause of dementia in younger individuals. There are no effective treatments for FTD. The most common known genetic cause of FTD is a mutation in the progranulin (PGRN) gene which leads to a decreased amount of PGRN protein in individual's brain and blood. PGRN may help neurons to grow and is also thought to be an important regulator of inflammation; low PGRN levels may cause FTD due to impairments in either of these processes. Recently, a number of drugs have been identified that can increase PGRN levels in laboratory models and animals, and some could soon be tested in human clinical trials for FTD. The best way to know in a short period of time whether these drugs work in humans is to see if they raise blood or cerebrospinal fluid PGRN levels. Although tests are available that can measure human PGRN levels, the factors that lead to variability in human PGRN levels are not well understood. For example, the time of day, what someone has had to eat, what medications they take or whether they have a mild infection could significantly alter PGRN levels and potentially interfere with studies to determine whether new drugs can raise human PGRN. The goal of this project is to determine how best to measure human PGRN levels, taking into account such potential interfering factors, so that sensitive clinical trials can be designed to test the effectiveness of new PGRN raising treatments. In addition, the study will look for other proteins or gene changes in the blood or spinal fluid that could also indicate a drug has effectively raised PGRN levels.