It was a great pleasure to host one of our Project Engagement Volunteer panel members for a visit to the lab last week. Chris Howe kindly wrote up a piece detailing his experience with us, offering some insights into our work and what he learned by joining us for the day. Thank you Chris!
(below) Chris trying his hand at pipetting a PCR plate for expression analysis of aquaporin-4.
It is the most incontrovertible truism to suggest that a diagnosis of degenerative brain condition devastates not only the individual but also the family too. These men and women who are forced to cope with the news of oncoming Alzheimer’s, Parkinson’s or Motor Neurone disease, face a raft of personal horrors beyond the understanding of most of us. They can only ask what can be done for them – which medicine can be taken and how can they try to live their normal life. They face a bleak scenario and although past research and drug development is there to help, there is much to do.
As an ex-teacher of history my personal scientific knowledge is weak – to say the least. My school boy biology helped me to tentatively grasp the development of a frog from a tadpole and that’s about all. A certain number of gaps in scientific knowledge are very much apparent. When I was asked to be part of a ‘lay persons’ group to look in to some of the progress that is being made in to neurodegenerative diseases at University College London, I was initially apprehensive and then keen to be involved. People (and especially the people affected by these diseases) should have some knowledge of the research that is being undertaken in this important sphere of medical research and how the various charities’ money is being used. And ultimately the destination of large and small donations needs to be rewarded by news of the work that is being done.
I was welcomed in to the laboratory offices by Dr Ian Harrison, Senior Research Fellow at UCL, who has recently been awarded an extension grant by Parkinson’s UK to continue his research. He led me through the labyrinth of floors and corridors to an open plan office and his ‘work station’. We sat and he explained what I might see on the day and then patiently took me through the rudiments of the causes of Parkinson’s disease (PD).
PD is caused by the build-up of a ‘rogue’ protein called Synuclein. In most peoples’ brains, Synuclein is a benign and even a contributory factor to the smooth firing of the synapses of the brain. A synapse is the point at which two neurons (brain cells) ‘talk’ to each other and stimulate thought and movement of the whole body. Synuclein helps this process. The problem begins to occur when Synuclein literally ‘gums up’ the works. Dr Harrison and his team are researching the causes for this malfunction.
The brain has a process through which waste material is removed. This is called the Glymphatic system. Essentially, cerebrospinal fluid is contained within ring-shaped spaces around the blood vessels of the brain. Under ordinary circumstances, the fluid carries unneeded debris away
and into the lymphatic system and all works perfectly. In PD this process becomes increasingly ineffectual and the disease spreads across the brain accordingly. For Dr Harrison, the big question is why this happens. If his team can identify the biochemical trigger point the appropriate drug can be developed to stop the damage.
Through their work at UCL the team have been focusing on a particular brain cell called Astrocytes. These cells have a crucial role to play in the removal of the protein Synuclein (and other debris) from the brain.
In this diagram the astrocyte cell is there linking the brain cell to the blood capillary. Dr Harrison explained that ‘feet’ of the astrocyte attach to the wall of the capillary. All around the capillaries beneath the feet themselves, water passes into the brain. This is through a protein called Aquaporin. The cutting-edge research, we have here, looks into the disposal of brain debris in the contra direction. For the layman, and me in particular, this is hard to understand. The debris removal is even more complex. Dr
Harrison tried to explain to me how this might be happening. His research suggests that dead and unwanted material passes into the ‘waste’ canals in between the astrocyte cell ‘feet’ through a kind of squeezing and absorbing process. A complex piece of brain science.
At the moment, he is looking into the function of the Aquaporin. There are many forms of this protein around the body (eleven) but only two of interest to Dr Harrison and his team – Aquaporin1 and Aquaporin4. Of these two it is Aquaporin4 (AQP4) that is the main focus of their attention. If AQP4 can be seen to be vital in the removal of waste – and in Parkinson’s sufferers this means the build of the Synuclein cells – why should it cease to work properly? Is this because the AQP4 is not working at all? Or is the Synuclein build stopping it from working. Simply stated questions but ones that involve incredibly complex thinking, planning, calculating and enactment of experiments as yet untried.
Well, not completely untried. The team at UCL have been working with a drug that shows that they may be on the right track. The spread of Synuclein across the brain can be traced and recorded using a process called Western Blot. On these diagrams the darker the mark the greater the concentration of Synuclein.
This is a random Western Blot test that shows increasing concentration. Dr. Harrison has been able to show, by
using this technique, how Synuclein builds up in the brains of mice over given periods of time.
Similarly, in a recent series of experiments and using the mentioned drug, the Western Blot test has clearly shown that the build-up of Synuclein has been significantly slowed. There are two parts – the Ipsilateral and the Contralateral. Dr Harrison’s work showed that when the mice were treated with the drug, less of the Synuclein spreads from the injected side of the brain, to the control side.
To me, this seemed very hopeful news. A slowing of the spread must be the object of all research and therefore a precursor to the minimalizing of the impact of the disease. However, like all good science, checks, checks and more checks need to be done. The drug involves, apparently, too high a concentration and, as such, is inefficient. Dr Harrison maintains that this just a small but positive step towards a golden destination.
The above tries to summarise my day at UCL with Ian. In addition, there was mention of fluorescent microscopy, million pound PET Scanners, MRI scanners, Polymerase Chain Reactions, enhanced RNA patterns, transcription factors and DNA. These additional aspects are integral to the study of neurodegenerative disease but beyond the explanation of this simple account. Indeed, beyond the explanatory skills of this simple unscientific man!
But, I did find my day as a lay observer in Ian Harrison’s lab absolutely fascinating. There were determined people working there. There were consistent trails being laid. I did find the minute detail of focus and the sheer insight almost impossible to take in but was constantly impressed. In my own studies in history, there is never anything ‘new’. There may be new interpretations of other people’s research and work or new evidence come to light. But nothing completely new. As my wife said when we talked through what I was doing in this report, my work related to the past. Ian Harrison’s work is of the future. And cures.