Cancer drug could be repurposed to provide treatment for brain aneurysms

An important class of drug used to treat cancer patients could be used to treat brain aneurysms, according to new research published this week. Brain aneurysms are a bulge in a blood vessel caused 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.

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 affected by brain aneurysms as they usually cause no symptoms until they rupture, but experts believe it could be anywhere from 1 in 100 to as many as 1 in 20 people.

Treatment is difficult, involving complex surgery which is currently only attempted in select cases. In a notable example, Game of Thrones actress Emilia Clarke suffered 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.

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 was unexpected, as mutations in this gene have been previously identified 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-associated 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.

Professor O'Driscoll said: "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.

"The lead authors and our collaborators on this paper based in the US, are now working on the next stages to test this drug further."

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.

Dr Manuel Ferreira, lead author of the report from the University Of Washington School Of Medicine, said: "We are now very close to treating these aneurysm patients with PDGFRB variants with specific receptor tyrosine kinase inhibitors".

Yigit Karasozen, Joshua W Osbun, Carolina Angelica Parada, Tina Busald, Philip Tatman, Luis F Gonzalez-Cuyar, Christopher J Hale, Diana Alcantara, Mark O'Driscoll, William B Dobyns, Mitzi Murray, Louis J Kim, Peter Byers, Michael O Dorschner, Manuel Ferreira Jr.
Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms.
AJHG, Report, Volume 104, ISSUE 5, P968-976, May 02, 2019. doi: 10.1016/j.ajhg.2019.03.014.

Most Popular Now

Aspirin green light for brain bleed stroke patient…

People who suffer a stroke caused by bleeding in the brain - known as brain haemorrhage - can take common medicines without raising their risk of another stroke, a major ...

Cancer cells are quick-change artists adapting to …

Until now, researchers have assumed that the growth of solid tumors originates from cancer stem cells characterized by specific surface markers, which develop in a fixed...

APRINOIA Therapeutics awarded grant from The Micha…

APRINOIA Therapeutics, a clinical-stage biotechnology company with a pipeline of therapeutics and imaging diagnostics for neurodegenerative diseases, announces today that...

Benralizumab not effective reducing exacerbations …

More than 15.3 million people in the U.S. suffer from chronic obstructive pulmonary disease (COPD), which is the third leading cause of death in this country, according t...

Pfizer announces top-line results from Phase 3 Tri…

Pfizer Inc. (NYSE: PFE) announced today that a Phase 3 study to assess the use of LYRICA® (pregabalin) as adjunctive therapy for epilepsy patients 5 to 65 years of age wi...

Novartis phase II data for new inhaled combination…

Novartis announced today that new phase II data for IND/GLY/MF (QVM149), an investigational, once-daily, fixed dose combination asthma treatment containing indacaterol ac...

New data show Symbicort reduces attacks in mild as…

New data from Novel START, an open-label trial designed to reflect real-world practice, has demonstrated the effectiveness of Symbicort Turbuhaler (budesonide/formoterol)...

Cannabis use among older adults rising rapidly

Cannabis use among older adults is growing faster than any other age group but many report barriers to getting medical marijuana, a lack of communication with their docto...

Merck pioneers new effort to see MS from the insid…

Merck, a leading science and technology company, joins the global multiple sclerosis (MS) community in recognition of World MS Day, an initiative created by the Multiple ...

Amgen joins with community oncology networks for n…

Amgen (NASDAQ: AMGN), along with leading community oncology networks, today announced the launch of Amgen Community Oncology Research Collaborators (ACORC), a new initiat...

Bayer receives U.S. FDA breakthrough therapy desig…

Bayer announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for copanlisib (Aliqopa™) for the treatment of adult patie...

Roche's personalised medicine entrectinib shrank t…

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced positive data from the Phase I/II STARTRK-NG study, evaluating the investigational medicine entrectinib in children and adole...