Could research techniques designed for frogs help spawn a cure for brain tumours?
Research techniques previously used to investigate the genetic makeup of frogs are being used at our Centre of Excellence at the University of Portsmouth to help improve our understanding of brain tumours.
Dr Rhiannon McGeehan has been building on earlier Leverhulme Trust-funded work she did at the Zoological Society of London, in collaboration with the Natural History Museum in London and the University of Portsmouth. Her work at our centre looking at mitochondria – or tiny energy producing structures present in every cell in our bodies - and a mutation known as F18L has now been published in the International Journal of Molecular Science.
Her paper shows the mutation in the mitochondrial DNA of some glioblastoma multiforme (GBM) tumour cells produce energy differently from those without the mutation.
Working in collaboration with nine institutions in total across the UK and France, the work has shown that the F18L mutation caused GBM cells to be 64% more sensitive to clomipramine, a repurposed drug commonly prescribed as an anti-depressant.
F18L can be detected by a simple blood test or swab so, potentially, it would be an effective and non-invasive method to help clinicians understand which of their patients might benefit from taking clomipramine in smaller doses so minimising the likelihood of side effects, which on very rare occasions can include high heart rate and liver problems, experienced by other patients.
Additional laboratory work at Portsmouth is already advanced in examining how effective clomipramine might be against brain tumours and it is hoped this will eventually lead to clinical trials in both adults and children. We will bring you more on this soon.
Dr McGeehan said: “Our discovery paves the way for clinical trials to include patients with F18L, as they may have a better chance of benefiting from clomipramine. After the trial, patients can be divided into subgroups e.g. with and without F18L in order to clarify the results: this is known as patient stratification.
“The benefit is that if you run a trial on 100 people and only 20% respond positively to the drug it might make the trial look relatively ineffective.
“But, if you know that everyone in that 20% had the F18L mutation, this means the drug works well for this type of patient. This is the foundation on which the future of personalised medicine is being built.”
Rhiannon’s interest in mitochondria and the crossover between frog and human mitochondrial DNA is what brought her to our centre at Portsmouth. We are proud to be funding her work.
As set out in our Manifesto 2019, drug repurposing is vital if we are to move closer to a cure and to give hope to patients and their families.