04:44pm Thursday 14 December 2017

Scientists discover common Diabetes drug reduces sight-threatening rise in brain pressure

Research led by the University of Birmingham, UK, published today in Science Translational Medicine, shows that a GLP-1 agonist drug, currently used to treat patients with Type II diabetes could be repurposed to treat raised brain pressure1.

Raised brain pressure is common in emergency situations such as traumatic brain injury, hydrocephalus and stroke, and is also the cardinal feature of Idiopathic Intracranial Hypertension (IIH), which causes disabling daily headaches and severely raised pressure around the nerves in the eye.  It also causes permanent vision loss in 25% of people2.

The Birmingham researchers examined whether GLP-1 agonist drugs could reduce intracranial pressure in an animal model of raised brain pressure, and found that the GPL-1 agonist exendin-4 reduces intracranial pressure both rapidly and dramatically.

Corresponding author Dr Alexandra Sinclair, of the University of Birmingham’s Institute of Metabolism and Systems Research, said: “Our findings show that exendin-4 reduces brain pressure within 10 minutes of dosing and by 44%, which is a greater extent than anything else we’ve tested before, and the treatment effects last at least 24 hours.

There are currently no bespoke treatments for IIH, which mostly affects women in their 20s and 30s.  The primary treatment in IIH is acetazolamide, but many patients deteriorate and remain unwell despite treatment and the drug also has such severe side effects that our previous trials have shown that 48 per cent of patients stop taking it.”

Obesity is the major causative risk factor for IIH2,3 and GLP-1 agonists cause weight loss in both diabetic and non-diabetic patients. Thus this new therapeutic approach provides both a direct treatment for raised brain pressure and also a disease modifying approach through driving weight loss in IIH.

The Birmingham team will be moving forward rapidly to clinical trials.

Alexandra Sinclair commented: “GLP-1 agonists are safe and widely used drugs for the treatment of diabetes which means that these findings are rapidly translatable into a novel treatment strategy for IIH.  They are also potentially game-changing for other conditions featuring raised brain pressure including stroke and brain trauma.”

The findings will be presented on September 8th and 9th in Vancouver at the International Headache Society Meeting, followed by the British Endocrine Society meeting in the UK from November 6th to 8th.

Exenatide, a synthetic version of exendin-4, has received Orphan Drug Designation for the treatment of Idiopathic Intracranial Hypertension from the European Medicines Authority and the US Food & Drug Administration4,5.

ENDS

 

About Idiopathic Intracranial Hypertension

  • Idiopathic Intracranial Hypertension is a rare condition, with an incidence in the general population of 1-2 per 100,000, rising to 20 per 100,000 in women who are obese.  However the incidence is rising dramatically in line with the global obesity epidemic
  • IIH is caused by raised intracranial pressure, resulting in chronic disabling daily headaches and optic nerve swelling leading to blindness in 25%
  • A previous study by the University of Birmingham research team has shown that weight loss is successful in relieving IIH.

 

Media enquiries

Dr Alexandra Sinclair is available for interview.

For further editorial information or to arrange a media interview, contact Ruth Ashton, Reputation and Communications Development Manager, University of Birmingham, at r.c.ashton@bham.ac.uk, +44 (0)121 414 8646, or +44 (0) 7989 558 041.

Investors

For further information about licensing or investment, contact: Dr Jonathan Watkins, Head of IP Services, University of Birmingham, at j.watkins.1@bham.ac.uk, or +44 (0)121 414 9090.

 

About the University of Birmingham

The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 5,000 international students from over 150 countries.

References:

  1. Botfield et al (2017). Glucagon-like peptide-1 receptor agonists as a therapeutic to reduce intracranial pressure. Science Translational Medicine.
  2. Markey et al (2016). Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions. Lancet Neurol 15(1): 78-91.
  3. From: https://nei.nih.gov/health/iih/intracranial, accessed 14 August 2017
  4. European Medicines Agency, EU/3/16/1629, accessed 14 August 2017
  5. S. FDA, Orphan Drug Designations and Approvals, accessed 14 August 2017

 


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