New drug to lower intracranial pressure could treat blinding headaches

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

Source: University of Birmingham

Patients with “blinding” headaches known as idiopathic intracranial hypertension (IIH) could be treated with an injectable peptide used in type 2 diabetes, a new study has found.

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

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

The study also showed a significant reduction in the number of headaches over the 12 weeks participants participated, with an average of 7.7 fewer headache days per month compared to baseline, compared to just 1.5 fewer days in the placebo arm .

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

“This is an important study for the rare and debilitating disease IIH, which can cause people, usually women, to go blind and suffer from debilitating daily headaches. There are currently no approved drugs to treat IIH, and so this finding is a major advance for IIH patients.

“We are pleased to see that the Phase 2 study resulted in our treatment group having lower intracranial pressure and almost 8 fewer headache days over the 12-week period both immediately and at 12 weeks, and all women continued treatment could consistently with few side effects. We now hope for a much larger study of exenatide to literally ease the pressure on the many people around the world who suffer 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, predominantly affects women aged 25 to 36 years, and weight gain is a major risk factor for developing IIH and disease recurrence.

The study also showed a significant reduction in the number of headaches over the 12 weeks participants participated, with an average of 7.7 fewer headache days per month compared to baseline, compared to just 1.5 fewer days in the placebo arm . The image is in the public domain

The once thought to be rare incidence of IIH is now increasing dramatically in line with the global rise in obesity, and there has been a 350 percent increase in incidence over the past 10 years. There are currently no approved drug options, and existing off-label drugs are complicated by unpleasant side effects.

A key finding was the drug’s rapid effect, with results suggesting that intracranial 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, if left untreated, can quickly lead to blindness.

dr James Mitchell, Lecturer in Neurology at the University of Birmingham and first author of the article, said:

“The results of this clinical study are a shot in the arm in finding clinical treatments for IIH. Although we need to conduct further studies before such a treatment could be available to patients in the future, we are encouraged by the significant results from this study, which have made a real difference for patients in the treatment arm, and this treatment may have benefits for conditions other than prove relevant which leads to increased intracranial pressure.”

In this study, the drug was injected into the subcutaneous tissue twice a day. To reduce the need for frequent injections in the future, a once-weekly subcutaneous injection called Presendin is being tested by Invex Therapeutics, a University of Birmingham start-up.

Shelly Williamson, Chair of Patient Advocacy IIH UK, said:

“This is such exciting progress. New drug options are critical for IIH, and this study brings hope to millions of patients living with the disease. We are very much looking forward to the next steps and to having the drug tested in two large phase 3 clinical trials.”

IIH Advance is a phase 3 clinical trial in adolescents being conducted in the UK and sponsored by the University of Birmingham, and IIH Evolve is being conducted in adults sponsored internationally by Invex Therapeutics. Ultimately, the aim is to gain enough evidence to approve the drug for use in IIH patients in the future.

About this news from headache and pharmacology research

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

Original research: Open 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 lower intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signaling.

Here we extrapolate these results to patients by conducting a randomized, double-blind, placebo-controlled study to evaluate the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters allowed long-term monitoring of intracranial pressure. The study enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure > 25 cmCSF and papilledema) who received subcutaneous exenatide or placebo. The three primary endpoints were intracranial pressure at 2.5 h, 24 h, and 12 weeks and alpha set a priori at less than 0.1.

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

These data provide confidence to proceed with a phase 3 study in idiopathic intracranial hypertension and underscore the potential to use GLP-1 receptor agonists in other disorders characterized by increased intracranial pressure.

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