2024 Alzheimer's Association Research Grant (AARG)

Neuroprotective Effects of "Hypothermia in a Syringe"

Can cooling the body in a controlled manner slow or prevent memory loss and the development of dementia?

Sonja Broeer, D.V.M., Ph.D.
Free University of Berlin
Berlin, Germany

Background

Hypothermia is a dangerous medical condition, often initiated by extended exposure to cold climates, in which body temperature drops too low. Recent studies with Alzheimer’s-like mice, however, have shown that cooling the body in a controlled manner may actually protect brain health and slow cognitive (brain function) decline. Specifically, they found that a protein called RNA-binding motif-3 (RBM3), which the body produces to protect itself during hypothermia, can prevent damage to synapses (connections between brain cells through which the cells communicate). Synapses are vital components of cognitive health. RBM3 was also shown to prevent nerve cell death and improve certain types of learning and memory. 

In preliminary studies, Dr. Sonja Broeer and colleagues discovered a mechanism for increasing levels of RBM3 to maintain brain health. They developed molecules called antisense oligonucleotides (ASOs), which are created from small fragments of DNA that can target specific genes in cells. They found that injecting these ASOs into cells grown in a laboratory dish could promote a three- to four-fold increase in RBM3 levels. This ASO treatment also increased RBM3 levels in mice engineered to develop prion disease (a type of brain disorder that also leads to memory loss), and it prevented disease-related nerve cell loss in the animals. 

Research Plan

For their current grant, Dr. Broeer and colleagues will test their ASO-RBM3 treatment on mice genetically engineered to develop Alzheimer’s-like brain changes. First, they will assess how the therapy affects various biomarkers (biological factors) of Alzheimer’s at an early stage, before the animals experience memory loss and other cognitive symptoms. These biomarkers include abnormal blood levels of dementia-related proteins (such as tau and neurofilament light chain [NfL]), as well as brain inflammation and declines in synaptic function. Next, they will determine how well the treatment can reverse cognitive and other symptoms of Alzheimer’s after the symptoms have developed. Lastly, Dr. Broeer and team will conduct similar tests with another mouse model, one that has been genetically engineered to develop high RBM3 levels.  

Impact

Results from this project could help clarify the biological mechanisms underlying RBM3’s role in brain health. It could also promote novel body cooling treatments for slowing or preventing dementia in humans – treatments that the researchers refer to as “hypothermia in a syringe.”