Personalised treatment of traumatic brain injury
Different patients recover differently from a traumatic brain injury. Researchers at Uppsala University are now aiming to develop a new drug that can be personalised to facilitate better recovery. The drug is based on a substance that stimulates cell renewal.
Currently, there are no drugs for treating brain injury, except one that helps prevent bleeding. And this is what Elham Rostami, a specialist in neurosurgery at University Hospital and docent at the Department of Neuroscience, wants to change. She will be testing a personalised treatment consisting of a substance that imitates a protein molecule called brain-derived neurotrophic factor (BDNF) in combination with a drug that inhibits cell death with the hope of improving patients’ chances of recovery.
“I believe there may be a genetic predisposition for recovering from a brain injury in which the gene that encodes BDNF plays a major role. I would also like to find out if everyone can take the drug and expect the same results, or if different patients, depending on variants of their BDNF gene, need different types of drugs,” says Elham Rostami, who is leading the project and has also been named a Wallenberg Clinical Fellow.
Cell renewal as well as cell death
So how does it work? The BDNF protein, which the test substance imitates, has the potential to facilitate both cell renewal and cell death when it breaks down. Both processes occur in all humans when it is broken down. But the extent to which it contributes to cell death or cell renewal after an injury depends on the genetic predisposition of the individual, i.e. what variant of the gene that encodes BDNF the patient has.
University Hospital and associate professor at the
Department of Neuroscience.
Photo: Mikael Wallerstedt
So what Rostami wants to investigate is whether drug treatment with the substance can help to stimulate cell renewal regardless of the gene variant a person has. This will be done in an in vitro study using stem cells produced from patients with traumatic brain injury who also have the important gene variant. This is where data from the Biobank and the brain injury registry will be greatly useful.
“This is fantastic because it records important parameters for patients who have been treated in our University Hospital. This allows us to evaluate the care they receive over time and it is also connected to the Biobank of blood samples used for genetic studies. In fact, the neurosurgery intensive care ward (NIVA) and the research structure around it were one of the reasons why I applied to study neurosurgery at Uppsala University. UCR and the Biobank offer fantastic opportunities and greatly facilitate research for clinicians like me,” says Elham Rostami.
Difficult to give an accurate prognosis
When patients are treated at NIVA, many parameters are monitored and the data stored which can then be analysed – in order to design personalised treatment and to facilitate a better prognosis. This is done using a range of AI models. But this method nevertheless has its weaknesses.
“Today it is very difficult for us to predict the prognosis for a patient. Our best algorithm can tell you the probability that the patient will survive (and in many cases it is a 50–60 per cent guess) but not very much about whether the patient can become independent again, or go back to work, or study for example,” says Elham Rostami.
In addition, traumatic brain injuries are complex in that the patient’s genes, lifestyle and cognitive capacity before the injury can also affect the outcome.
Need for ongoing support
Every year, around 10 per cent of patients with a traumatic brain injury in Sweden suffer such serious injuries that we have to assume that they will need some form of ongoing support, in some cases even full-time assistance. But some of these patients recover so well that after three to five years they can live independently and even, as in a few cases, go to university.
“I was rather surprised when I met these patients on their follow-up consults. So these patients can teach us a lot about important factors and what we can do,” says Elham Rostami.
In spring 2020 she initiated a study of COVID-19 patients with neurological symptoms. By analysing samples of their spinal fluid, signs of damage to the brain could be detected that were not apparent in routine tests. The study was a collaboration between the Karolinska Institute, Stockholm University, the University of Gothenburg and several groups at Uppsala University.
Improving the brain’s recovery
Elham Rostami’s hope is to better understand the different types of traumatic brain injury and how these patients will manage in the future – and whether you can pharmacologically improve the brain’s recovery.
But whether COVID-19 patients might also benefit from the substance is not yet known.
“We must first prove that the treatment has the effect we think it will have. And then of course the effects on the brain after COVID-19 infection differ very greatly from that of traumatic brain injury. We also have so much left to understand when it comes to COVID-19. We have to first see what kind of brain injuries they have, and whether these are permanent,” says Elham Rostami.
So what do you hope your research will lead to?
“I hope that as many as possible will be able to recover well and do well again in their lives. Putting a time frame on this is something you should never do, but within ten years I hope there will be more pharmacological alternatives for treating brain injuries.”
Testing a substance to treat brain injuries
- Elham Rostami is going to test a substance that imitates BDNF but has fewer toxic side effects, combined with a drug that reduces the risk of cell death.
- Using the brain injury registry and Uppsala’s Biobank with its detailed data, we hope to be able to create a better understanding of how well patients will recover in the future.