Scientists claimed to have discovered a way in the fight against glioblastoma – the most aggressive type of brain tumour – by using a strain of salmonella, that usually causes food poisoning.
The researchers, which include those of Indian origin, at the Duke University genetically modified Salmonella typhimurium into a cancer-bursting weapon that produces self-destruct orders deep within tumours.
Tests in rat models with extreme cases of the disease showed a remarkable 20 percent survival rate over 100 days – roughly equivalent to 10 human years – with the tumours going into complete remission.
Previous studies have shown, quite accidentally, that the presence of bacteria can cause the immune system to recognise and begin attacking tumours. However, follow-up clinical trials with genetically detoxified strains of S typhimurium have since proven ineffective by themselves.
To use these common intestinal bacteria as tumour-seeking missiles, researchers including Nalini Mehta and Ravi Bellamkonda, selected a detoxified strain of S typhimurium that was also deficient in a crucial enzyme called purine, forcing the bacteria to seek supplies elsewhere.
Tumours just so happen to be an excellent source of purine, causing the bacteria to flock to them in droves.
The biomedical engineers then made a series of genetic tweaks so that the bacteria would produce two compounds called Azurin and p53 that instruct cells to commit suicide – but only in the presence of low levels of oxygen.
Since cancerous cells multiply energetically, the environment around tumours has unusually low oxygen.
“A major challenge in treating gliomas is that the tumour is dispersed with no clear edge, making them difficult to completely surgically remove,” said Bellamkonda. “So designing bacteria to actively move and seek out these distributed tumours, and express their anti-tumour proteins only in hypoxic, purine rich tumour regions is exciting,” he said.
“At the doses we used in the experiments, they were naturally cleared once they’d killed the tumours, effectively destroying their own food source,” he added.
Glioblastoma is hard to treat with medications as the blood-brain barrier – a protective sheath separating brain tissue from its blood vessels – prevents most chemicals from reaching it, making it difficult to attack the disease with drugs. Because of this, survival rates are extremely low for those diagnosed with the condition.
Even with the best care currently available, median survival time is a dire 15 months, and only 10 per cent of patients survive five years once diagnosed.
The findings have been published in the journal Molecular Therapy – Oncolytics.
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