Rabies virus opens a new avenue to cancer treatment

Credit: GerryShaw via Wikimedia Commons.

Rabies is one of the most severe viral diseases on the planet. Despite the development of vaccinations and treatments, it still results in high mortality. The reasons for this include the virus’s ability to evade the immune system for some time, and its ability to target the brain. Certain experimental treatments, such as induced coma, are available at the later stages of the disease, but none of them are particularly effective. Fatal encephalitis is an unavoidable result of a rabies infection in almost all cases.

But humans would not be what they are now if they did not have the ability to find the most creative approaches to various hardships that nature throws at them. Even though rabies itself has not been completely tackled, we have a few things to learn from its causative agent. The trait that makes the rabies virus so deadly is its ability to cross the blood-brain barrier (BBB) – a semipermeable membrane that allow only very small molecules to pass into the fluid surrounding the brain. The rabies virus has developed an ability to bypass that hindrance. The virus has a molecule termed glycoprotein on its surface that binds to specific receptors expressed on neuronal cells. The elongated shape of the virus aids its binding to the receptor and entry into neurons.

The virus has already been used as a research tool: virus particles that move from neuron to neuron can be tracked using fluorescent labelling and, thus, are used to trace synaptic connections (the points at which neurons interact with one another). Recently another way to exploit unique abilities of the rabies virus has emerged. This mechanism of crossing the BBB has been utilised by a few research groups in South Korea, putting their collaborative effort into developing a treatment for brain tumours. Crossing the BBB is one of the main hurdles facing the delivery of anti-cancer drugs to the brain. The researchers developed a mimetic of the rabies virus – gold nanorods coated with molecules derived from the rabies surface glycoprotein that allows the virus to enter the cell. Gold was a material of choice due to its specific characteristics: it is flexible enough to assume a variety of shapes and, hence, is a good candidate to mimic a unique bullet-like shape of the rabies virus; and it’s also inert and non-toxic, thus should have low or no reactivity with the host. Studies demonstrated that both the shape and the presence of the surface glycoprotein-derived molecules significantly increased the uptake of the particles into neurons.

Another attractive prospect of the particles is their utilisation in a cancer treatment called ‘hyperthermic’ treatment. Tumours are thought to be more susceptible to elevated temperatures than healthy tissues. Temperatures as high as 45⁰C can have an effect on cancer cells. Once the rabies particles reach the tumour they undergo a near-infrared irradiation, which increases their temperature and, subsequently, the local temperature within the tumour. This way the rabies mimetic offers a way to a more targeted therapy. Though this is the early days for the rabies-inspired nanorods, they nevertheless offer a promising strategy for brain cancer treatment. Not only is it a clever design and impressive body of work, but it is also an inspiring manifestation of human ingenuity, whereby one deadly disease can be harnessed to tackle another.

 

This article was written by Alina Gukova and edited by Bonnie Nicholson.

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