Haematology

The study find that drug used to treat cancer patients  use to treat brain aneurysms, according to new research publish this week. Brain aneurysms are a bulge in a blood vessel cause by a weakness in the blood vessel wall. As blood passes through the weakened blood vessel; blood pressure causes a small area to bulge outwards.

Treat brain aneurysms

They can develop anywhere in the body but are most common in the abdominal aorta (the artery that carries blood away from the heart) and the brain. It’s difficult to estimate exactly how many people are affect by brain aneurysms as they usually cause no symptoms until they rupture; but experts believe it is anywhere from 1 in 100 to as many as 1 in 20 people.

Treatment is difficult, involving complex surgery which is currently only attempt in select cases. In a notable example; Game of Thrones actress Emilia Clarke suffer from two aneurysms while filming the series; undergoing surgery as a result. Working in collaboration with colleagues at University of Washington School of Medicine in Seattle, USA, scientists at the University of Sussex may now have found a safer and more efficient possible treatment involving ‘Receptor tyrosine kinase inhibitors’; a class of drug currently used to treat cancer.

Involving complex surgery

Using sophisticated ‘next generation’ DNA sequencing technologies; teams in Washington lead by Manuel Ferreira; Associated Professor of Neurological Surgery; identified a new genetic basis of a form of brain aneurysm (mutations PDGFRB). This is unexpect; as mutations in this gene have been previously identify in completely different human developmental disorders.

Mark O’Driscoll, Professor of Human Molecular Genetics at the Genome Damage and Stability Centre at the University of Sussex; then found that multiple disease-associate mutations in PDGFRB caused a specific abnormality in its encoded protein. This abnormality causes its activity to remain locked in a hyper-active form, referred to as ‘gain-of-function variants’ in effect; causing the protein to always be ‘turned-on’.

Publishing their findings in this months’ edition of the American Journal of Human Genetics; the Sussex team also demonstrated that this abnormal form of the protein can, in some cases, be countered by a drug which is currently used in cancer treatments.

Disease-associated mutations

Drug repurposing is not unheard of, and there are already some success stories including the use of thalidomide as a treatment for leprosy as well as a blood cancer called multiple myeloma. This is an extremely exciting discovery which shows how basic lab-derived observations on a genetic level can move into a clinical setting and start making big changes to public healthcare and treatments.

Our research focused primarily on understanding the genetic and cellular mechanisms underlying a particular type of aneurysm. By finding a new genetic basis in some patients; we were also able to demonstrate that a known cancer drug could counter this genetic basis in most instances. Understanding the genetics behind diseases like this is crucial in identifying possible treatments and next steps – and that is exactly what our part in this new research has shown.