Oxford University spinout Oxford Brain Diagnostics Ltd is hoping to unlock some of these clues by introducing a new test that can spot the signs of dementia as early as possible, allowing for earlier intervention and better clinical research.
“The signs and symptoms of dementia are very subtle in the earlier stages,” says Dr Steven Chance, the company’s co-founder and CEO. “We need more accurate and better biomarkers both for drug development and to help clinicians make the right decisions earlier in the process for patients and their families.”
Advanced clinical diagnosis methods have usually focused on measuring the build-up of amyloid plaques and/or tau tangles, which represent the main hypothesis about what actually causes Alzheimer’s disease.
Examining the neuronal networks in the grey matter during the early stages of dementia symptoms has the potential to provide microscopic insights into neurodegeneration. OBD’s method – CDM (Cortical Disarray Measurement) focuses on measuring the subtle micro-anatomical changes that are happening in the brains’ cortex by using MRI with Diffusion Tensor images.
This novel approach was born of Chance’s research into neuropathology, where he analysed brain samples through a microscope.
“Over the last decade, I found that a consistent issue in all the analyses was the changes that were happening in the brain with age. These findings guided me towards Alzheimer’s disease where I discovered that cortical disarray could potentially shed a light on the diagnosis of the disease condition. I realised that the insight we can gain by looking at the brain through the microscope was not really being used in clinical practice with living dementia patients, because there’s no way to get access to that information in life.
OBD can extract the data from MRI scans of the brain in living subjects.
“We originally scanned human brains, then compared the exact same part of the brain directly through the microscope, looking at a series of detailed anatomical measurements in order to compare the histology directly with the MRI data,” explains Chance. “That enabled us to begin interpreting the measurements we’re making.”
This method is much more sensitive to subtle effects, which can aid early prediction, differential diagnosis and testing new drugs.
Importantly, it also circumvents debate over whether the amyloid hypothesis is correct, or whether to use amyloid or tau as a biomarker.
“Whatever hypothesis you have about the mechanism of Alzheimer’s disease, they all converge on the neurodegeneration in the brain,” says Chance.
This approach can also apply to other neurological diseases like multiple sclerosis or schizophrenia, and Chance says the company is interested in exploring those spaces as well.
He says that OBD’s goal is to become the gold standard for measuring neurodegeneration in dementia.
“Pharmaceutical companies are facing all sorts of challenges. In the last two decades there have been hundreds of trials that have failed to produce any new disease-altering drugs for Alzheimer’s.
“We can help drug companies improve their discovery process by enriching their patient cohorts and making sure that they get the right individuals in the trials.
“We can also enable them to measure the benefits of their drugs at that subtle microscopic level, and improve their classification of disease for stratifying patients to make sure the right people receive the right treatments.”