Eureka Staff

Gray Matters: Biomarker Signatures for Batten Disease (Video)

A critical element of drug discovery is identifying biomarkers. In Batten disease, it's being taken in a different direction. Eureka's live coverage at Neuroscience 2018.

Biological markers or simply biomarkers refer to a broad subcategory of medical signs—from in vitro assays of tissue and blood to molecular imaging, lipid tests and genetic mutations—that can be measured accurately and reproducibly.

For rare diseases like Batten, this presents a problem. Batten is the common name for a series of inherited disorders known as neuronal ceroid lipofuscinoses or NCLs. Single biomarkers in this field have been the elusive Holy Grail for the last couple of decades, so Sanford Research in South Dakota in collaboration with Charles River have been taking an innovative approach by developing a scoring system for monitoring Batten disease in a mouse model of CLN6-Batten disease. 

They are combining imaging and behavior data, such as PET, MRI and kinematic analysis, to provide longitudinal disease monitoring. Over the long run, this could contribute to improvements in early diagnosis, tracking progression of the disease, and monitoring response to treatment in both clinical and research environments.

"We are combing a range of additional tools during course of disease progression, such as imaging tools, metabolic activity and motor function and then combine them together to perform a detailed analysis", said Antti Nurmi, Managing Director of Charles River's Discovery CNS site in Kuopio, Finland. "From that we can extract objective, meaningful readouts that can be used to investigate models in a more detailed fashion."

Some of this work is on display this week at the Society for Neuroscience meeting in San Diego. Charles River is presenting three posters about Batten disease and specifically different aspects of this scoring system. One poster looks at how kinematic analysis, which is concerned with temporal aspects of motion, such as positions, angles, velocities, and accelerations of body segments and joints during motion, is being used to track differences in the gait of Batten disease rodent models from an early age.

A second poster also describes how kinematic analysis and advanced brain imaging are being used to monitor changes in the brains of a Batten model that expresses a different form of Batten disease. A third poster described progressive and profound changes in brain anatomy, brain metabolism and gait using a statistical technique that allows you to identify which variables in a sea of data are most associated with progression of Batten disease.

"In Batten disease there is a small but active community of foundations and patient advocacy groups who have kept Batten disease and other diseases like it from being left in the dark, or at least lagging behind other more common neurological diseases," said Nurmi. "For scientists like us, that is exciting to see."

You can learn more about Batten disease by watching the Gray Matters video, which is highlighting hot topics at this year's SfN meeting. Also, look for new installments of Gray Matters over the next few days, where you will be hear about drugs that inhibit the LRRK2 gene -- a hot new area in Parkinson's research -- and what functional ultrasound can tell us about a rat's brain.