New drug to reduce brain pressure could treat blinding headaches

Summary: Exenatide, an injectable peptide currently in phase two clinical trials for the treatment of type 2 diabetes, reduces symptoms of blinding headaches associated with idiopathic intercranial hypertension, a new study reports.

Source: University of Birmingham

Patients with ‘blinding’ headaches known as idiopathic intercranial hypertension (IIH) could be treated with an injectable peptide used for type 2 diabetes, according to a new trial.

The study, published in the journal Braintoday reports on a Phase 2 trial of a drug called exenatide, a GLP-1 receptor agonist, as a potential treatment for IIH.

The IIH pressure trial conducted by a team of neurologists from the University of Birmingham and Birmingham University Hospitals found that for the seven patients who received regular injections of the drug, currently approved for use in type 1 diabetes 2, caused a drop in pressure in the brain during both short-term (2.5 hours and 24 hours) and long-term (12 weeks) measurements.

The trial also saw significant reductions in the number of headaches over the 12 weeks that participants participated, with an average of 7.7 fewer headache days per month from baseline, compared to only 1.5 days less in the placebo arm.

Alex Sinclair is Professor of Neurology at the Institute for Metabolism and Systems Research at the University of Birmingham, Honorary Consultant Neurologist at University Hospitals Birmingham NHS Foundation Trust and Principal Investigator of the study. Professor Alex Sinclair said:

“This is a major trial for the rare and debilitating disease IIH which can lead to people, usually women, going blind and suffering debilitating daily headaches. There are currently no approved drugs to treat IIH, so this finding is a major step forward for patients with IIH.

“We are delighted to see that the phase two trial resulted in our treatment group having lower brain pressure both immediately and after 12 weeks and almost 8 days less headache over the period. of 12 weeks, and that all women were able to continue treatment throughout with few adverse effects.We now hope to see a much larger trial of exenatide to literally take the pressure off for the many people around the world suffering from ‘IIH.

Shot in the arm for IIH treatment

Idiopathic intracranial hypertension (IIH) is a debilitating condition that increases pressure in the brain and can lead to chronic headaches and even permanent vision loss. The disease, which often leaves patients with a reduced quality of life, mainly affects women between the ages of 25 and 36, and weight gain is a major risk factor for developing IIH and disease relapses.

This shows a cartoon of a person with a headache
The trial also saw significant reductions in the number of headaches over the 12 weeks that participants participated, with an average of 7.7 fewer headache days per month from baseline, compared to only 1.5 days less in the placebo arm. Image is in public domain

Once thought to be rare, the incidence of IIH is now increasing dramatically alongside the global rise in obesity and there has been a 350% increase in incidence over the past 10 years. Currently, there are no licensed drug options, and existing drugs used off-label are complicated by bothersome side effects.

A key finding was the rapid action of the drug, with results indicating that brain pressure was significantly reduced within two and a half hours of taking the drug. This rapid onset of action is vital in a condition that can cause rapid blindness if left untreated.

Dr James Mitchell, senior lecturer in neurology at the University of Birmingham and first author of the paper, said:

“The results of this clinical trial are a boost in finding clinical treatments for IIH. Although we need to do further trials before such a treatment can be available to patients in the future, we are encouraged by the significant results of this trial which made a real difference for those in the treatment arm and this treatment may prove relevant for other conditions causing increased brain pressure.

In this study, the drug was given by injection twice a day into the subcutaneous tissue. To reduce the need for frequent injections in the future, a weekly subcutaneous injection called Presendin will be trialed by University of Birmingham start-up Invex Therapeutics.

Shelly Williamson, chair of the IIH patient charity UK, said:

“This is such exciting progress. New drug options are vitally important for IIH and this trial brings hope to the millions of patients living with the disease. We look forward to the next steps and to see the drug being tested in two large phase 3 clinical trials.”

The IIH Advance is a phase 3 clinical trial in adolescents conducted in the UK, sponsored by the University of Birmingham and the IIH Evolve is ongoing in adults sponsored internationally by Invex Therapeutics. Ultimately, the goal is to get enough evidence to allow the drug to be licensed for use in IIH patients in the future.

About this headache and current pharmacology research

Author: Tim Mayo
Source: University of Birmingham
Contact: Tim Mayo – University of Birmingham
Picture: Image is credited to Neuroscience News and was created with DALL-E 2 AI technology

Original research: Free access.
“The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial” by Alex Sinclair et al. Brain


The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data demonstrated a novel strategy for lowering intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signaling.

Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in intracranial hypertension. idiopathic. Telemetric intracranial pressure catheters have allowed long-term monitoring of intracranial pressure. The trial recruited adult women with active idiopathic intracranial hypertension (intracranial pressure > 25 cmCSF and papilledema) who received subcutaneous exenatide or placebo. The three primary outcomes were intracranial pressure at 2.5 h, 24 h and 12 weeks and the alpha set First of all less than 0.1.

Of the 16 women recruited, 15 completed the study (mean age 28 ± 9 years, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and significantly lowered intracranial pressure at 2.5 h −5.7 ± 2.9 cmCSF (P = 0.048); 24 h −6.4 ± 2.9 cmCRL (P = 0.030); and 12 weeks −5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signal was noted.

These data provide confidence to proceed with a Phase 3 trial in idiopathic intracranial hypertension and highlight the potential for use of the GLP-1 receptor agonist in other conditions characterized by elevated intracranial pressure.

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