Year/Course: 2014-2015, Lent 2015
Project type: Medical

Contact: Professor David Klenerman FRS, Dr. Steven F. Lee, Dr. Mathew H. Horrocks, Chemistry

Diagnosis of neurodegenerative diseases such as Parkinson’s Disease and Alzheimer’s Disease can only be done definitively by post-mortem analysis of the brain. Since the brain compensates for damage, clinical symptoms will typically only appear when as much as 70% of the brain neurons have already been lost, leaving limited scope for treatment since neurons usually do not regenerate.

Within the brain, particular proteins (which differ in the different diseases) can clump together forming structures called oligomers and eventually fibrils which will accumulate into the larger plaques used for post-mortem diagnosis. The most recent research suggests that it is this intermediate phase, the oligomer structures, which cause the damage to the neurons.

The difficulty of detecting oligomers is that their concentration is very low. Within a solution of proteins ~1% will be in oligomeric form, and in brain and spinal fluid the concentration of the monomers is already relatively low. Instead of a bulk measurement approach, the researchers have developed a technique which can label, detect and count the individual oligomers from a sample of spinal fluid. Initial tests in a small number of patients with and without Parkinson’s Disease do show that people with clinical symptoms have a higher concentration of the oligomers, as measured using this technique, which represents the first ever experimental detection of single molecules from human patients.

The challenge for the i-Team is to investigate and identify the next steps that the researchers should take to develop this into a medically-accepted and widely-used test. Some example questions include: Having proved the basic science, what other evidence will be needed for this to be adopted? Where would a test be of most value – in new drug development programs, in clinical practice, or in gaining a better understanding of the mechanisms of these diseases? Who else is working in this area, both commercially and academically, and who might be interested in partnering in the future development? What other diagnostic markers are being developed, and how widely are oligomers recognised at this stage?

The answers that the i-Team develops will be critically important in helping the inventors take the required next steps for this technology to move from scientific research to a test that can improve the lives of billions of people.