Subarachnoid haemorrhage is when a brain aneurysm ruptures and causes a bleed into the brain. It is a life changing event and most patients that survive are left disabled to some degree. Currently all available treatments are directed at securing the aneurysm to prevent any further bleeding. Unfortunately the blood widely covers the brain and it is not possible to simply remove it with surgery. It is therefore left to slowly breakdown by the body’s own mechanisms.
Haptoglobin is a substance that elsewhere in the body binds and helps breakdown blood. Unfortunately it is not present in the brain and this does not help in patients with subarachnoid haemorrhage. A team of scientists and doctors from Wessex Neurological Centre have therefore been investigating if there are ways that haptoglobin can be given to patients to improve their recovery from subarachnoid haemorrhage. Smile for Wessex have been critical to the success of this by supporting the work to assess if this is likely to work.
The first step has been to obtain clinically useable haptoglobin. To do this we have collaborated with BioProducts Laboratory (BPL) to find new ways to produce this. We have then tested the safety of this by exposing normal brain cells to it in the laboratory. We have then shown how increasing amounts of blood cause increasing amounts of damage to these brain cells and how adding haptoglobin to them protects them from the damage from the blood. The results are due to be presented at the international conference on Neurovascular Events after Subarachnoid Haemorrhage and will be published into a scientific journal.
The grant has been critical to cementing the team of different experts together and generated the much needed data to allow the team to apply for further research grants and continue the development of haptoglobin and hopefully will ultimately lead to a new treatment for future patients.
Bleeding in the brain can either be life threatening or seriously impact on a person’s ability to live independently. It effects the lives of patients’ family and friends, and is a significant cost to the NHS. Currently, treatment options are limited and research is vital to reduce the personal and social costs this condition causes.
When bleeding occurs the body has a natural defence to prevent injury, which includes the action of a protein called haptoglobin. At Southampton University and NHS trust, we have assembled a team of scientists, medics, and industrial collaborators to investigate haptoglobin as a novel treatment for bleeding in the brain. Funding from Smile 4 Wessex (S4W) has played an essential role in maintaining the continuity of this team and its research.
Work to develop haptoglobin as a viable option for brain bleeds has been split between research facilities at BioProducts Laboratory (BPL) and the University of Southampton. We have worked extensively with BPL to develop a method to produce large quantities of clinical grade haptoglobin. S4W funding has been essential to test this product for safety and efficacy. We have established a ‘brain in a dish’ model and shown that challenging it with blood results in the death of it’s neurons, which are the major cells of the brain. However, when we include BPL’s haptoglobin this injury is fully prevented. We have tested a range of blood concentrations and clearly show that BPL’s haptoglobin is effective up to and including the amount of blood seen in patients following a brain bleed.
Our research is focused on a subtype of brain bleed called ‘subarachnoid haemorrhage’ (SAH). Using a model of SAH, we have clearly shown that blood at a concentration seen in patients can result in injury to the brains neurons, which is also associated with inflammation. However, when haptoglobin is included in the experiment this injury and inflammation is fully reversed. This result is the first to show that a clinical-grade preparation of haptoglobin can reverse the blood driven injury seen in SAH patients.
We are currently preparing a manuscript to report our findings to the international science community. We have also been selected to present our results at Vasospasm, the major conference for researchers working in the SAH field. The work funded by S4W will provide the science community working on SAH and other brain bleeds with tools and ideas to further their research. In particular, S4W funding has contributed to moving haptoglobin a significant step forward towards a viable treatment option in SAH and other brain bleeds.