One Minute Insight
Professor Ken Smith talks about the work in immune diseases and finding new treatments that can help patients
A swift ‘kick and kill’ for the HIV virus
HIV is a life-long infection that targets the immune system and weakens your ability to fight infections and cancer when it is untreated. Some viruses hide in a sleeping or ‘latent’ state and cannot be reached by current therapies, meaning that suppressive drug treatment must be lifelong.
A new approach to wake this latent virus and destroy it ‘kick and kill’ was the approach of researchers from Cambridge, Oxford and London. Cambridge developed a novel assay to detect whether the latent virus had been depleted, without which it would be difficult to validate any curative effect.
Clinicians, virologists, immunologists and molecular biologists ran a large clinical trial to try and eradicate HIV from infected patients.
The trial which lasted three years looked at 60 men recently diagnosed with HIV. All of them showed a good response to conventional therapy, however, the ‘kick and kill’ approach was not strong enough to reduce the amount of latent virus as measured by Cambridge researchers, and other, assays.
The study however has provided a benchmark from which to trial different combinations of therapies to tackle HIV and investigate new strategies to destroy dormant virus. Meanwhile patients continue to benefit from advances in suppressive therapy which, when successful is giving them a normal lifespan.
This was the question a mum of a daughter with the rare inflammatory bone disease CRMO asked rheumatologist Dr Jagtar Singh Nijjar at the Rare Disease Day evening lecture, which took place in 2017.
Two years on, Dr Nijjar gave a talk at the 2019 Rare Disease Day evening lecture, hosted by the NIHR BioResource and the Cambridge Rare Disease Network, about what followed from that chance meeting.
Listen to this edited transcript of his talk (3:13 mins). Click to listen to the full lecture.
Genetic variants found that determine severity of Crohn’s disease
People with Crohn’s disease have inflammation in their digestive systems, leading to problems such as abdominal pain, weight loss, diarrhoea and fatigue. ts origins are complex. While no single gene has been identified as the ‘main’ cause, over 150 genetic differences (called ‘variants’) have been identified that increase the risk of the disease.
One of the biggest challenges that doctors face in treating Crohn’s disease is that the behaviour of the disease can vary considerably between people, with some experiencing very aggressive disease and others having a much milder form. It was previously thought that the more variants people had, the more likely they would be to have a more aggressive form of Crohn’s disease, but Cambridge researchers have shown that this is not the case.
By comparing the genomes (the complete set of all the genes) of more than 2,700 people who have either mild or aggressive Crohn’s disease, the researchers showed that while there were variants that influenced prognosis, these were different from the variants that caused the disease to develop in the first place.
Finding that the genes involved in determining disease course differ from those that cause Crohn’s disease to develop has wide-ranging and important implications. It suggests, for example, that the best targets for new therapies might not be the pathways that have previously been thought to be important in Crohn’s disease, but rather new pathways in which the prognosis-associated genes are involved. This work – to better understand how these genes might alter prognosis – is ongoing and should provide better ways of treating Crohn’s disease in the future.
B-cells are a type of white blood cells that can produce harmful auto-antibodies which attack the body tissue. This can lead to conditions such as vasculitis, when the immune system attacks blood vessels and it can be serious in some people.
Cambridge researchers have looked at the effect of depletion of B cells with a drug called Rituximab.
Through pilot and controlled studies, researchers have looked at the long-term benefit of Rituximab and how this drug would suit patients with vasculitis. This has led to rituximab being accepted into the NHS commission guidance and national guidelines.