119
Views
0
CrossRef citations to date
0
Altmetric
Review

Experimental drugs for the treatment of idiopathic intracranial hypertension (IIH): shedding light on phase I and II trials

, ORCID Icon, , & ORCID Icon
Pages 1123-1131 | Received 03 Oct 2023, Accepted 22 Nov 2023, Published online: 25 Nov 2023

References

  • Mollan SP, Davies B, Silver NC, et al. Idiopathic intracranial hypertension: consensus guidelines on management. J Neurol Neurosurg Psychiatry. 2018 Oct;89(10):1088–1100. doi: 10.1136/jnnp-2017-317440
  • Thaller M, Homer V, Hyder Y, et al. The idiopathic intracranial hypertension prospective cohort study: evaluation of prognostic factors and outcomes. J Neurol. 2023 Feb;270(2):851–863. doi: 10.1007/s00415-022-11402-6
  • Mollan SP, Grech O, Sinclair AJ. Headache attributed to idiopathic intracranial hypertension and persistent post-idiopathic intracranial hypertension headache: a narrative review. Headache. 2021 Jun;61(6):808–816. doi: 10.1111/head.14125
  • Mollan SP, Wakerley BR, Alimajstorovic Z, et al. Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension. J Headache Pain. 2021 Oct 7;22(1):118. doi: 10.1186/s10194-021-01321-8
  • Hyder YF, Homer V, Thaller M, et al. Defining the phenotype and prognosis of people with idiopathic intracranial hypertension after cerebrospinal fluid diversion surgery. Am J Ophthalmol. 2023 Jun;250:70–81. doi: 10.1016/j.ajo.2023.01.016
  • Mollan SP, Bodoza S, Ní Mhéalóid Á, et al. Visual field pointwise analysis of the idiopathic intracranial hypertension weight trial (IIH: WT). Transl Vis Sci Technol. 2023 May 1;12(5):1. doi: 10.1167/tvst.12.5.1
  • Piccus R, Thaller M, Sinclair AJ, et al. Current and emerging diagnostic and management approaches for idiopathic intracranial hypertension. Expert Rev Neurother. 2023 May;23(5):457–466. doi: 10.1080/14737175.2023.2206567
  • Mollan SP, Aguiar M, Evison F, et al. The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019 Mar;33(3):478–485. doi: 10.1038/s41433-018-0238-5
  • Daniels AB, Liu GT, Volpe NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007 Apr;143(4):635–641. doi: 10.1016/j.ajo.2006.12.040
  • Mollan SP, Tahrani AA, Sinclair AJ. The potentially modifiable risk factor in idiopathic intracranial hypertension: body weight. Neurol Clin Pract. 2021 Aug;11(4):e504–e507. doi: 10.1212/CPJ.0000000000001063
  • Mollan S, Hemmings K, Herd CP, et al. What are the research priorities for idiopathic intracranial hypertension? A priority setting partnership between patients and healthcare professionals. BMJ Open. 2019 Mar 15;9(3):e026573. doi: 10.1136/bmjopen-2018-026573
  • Hornby C, Mollan SP, Botfield H, et al. Metabolic concepts in idiopathic intracranial hypertension and their potential for therapeutic intervention. J Neuroophthalmol. 2018 Dec;38(4):522–530. doi: 10.1097/WNO.0000000000000684
  • Hornby C, Botfield H, O’Reilly MW, et al. Evaluating the fat distribution in idiopathic intracranial hypertension using dual-energy X-ray absorptiometry scanning. Neuroophthalmology. 2018 Apr;42(2):99–104. doi: 10.1080/01658107.2017.1334218
  • Westgate CS, Botfield HF, Alimajstorovic Z, et al. Systemic and adipocyte transcriptional and metabolic dysregulation in idiopathic intracranial hypertension. JCI Insight. 2021 May 24;6(10): doi: 10.1172/jci.insight.145346
  • Adderley NJ, Subramanian A, Nirantharakumar K, et al. Association between idiopathic intracranial hypertension and risk of cardiovascular diseases in women in the United Kingdom. JAMA Neurol. 2019 Sep 1;76(9):1088–1098. doi: 10.1001/jamaneurol.2019.1812
  • Thaller M, Mytton J, Wakerley BR, et al. Idiopathic intracranial hypertension: evaluation of births and fertility through the hospital episode statistics dataset. BJOG. 2022 Nov;129(12):2019–2027. doi: 10.1111/1471-0528.17241
  • Thaller M, Adderley NJ, Subramanian A, et al. Co-morbid polycystic ovarian syndrome with idiopathic intracranial hypertension. Neuroophthalmology. 2023;47(1):49–52. doi: 10.1080/01658107.2022.2162089
  • O’Reilly MW, Westgate CS, Hornby C, et al. A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics. JCI Insight. 2019 Mar 21;4(6). doi: 10.1172/jci.insight.125348
  • van Rossum EF. Obesity and cortisol: new perspectives on an old theme. Obesity (Silver Spring). 2017 Mar;25(3):500–501. doi: 10.1002/oby.21774
  • Westgate CSJ, Markey K, Mitchell JL, et al. Increased systemic and adipose 11β-HSD1 activity in idiopathic intracranial hypertension. Eur J Endocrinol. 2022 Aug 1;187(2):323–333. doi: 10.1530/EJE-22-0108
  • Mollan SP, Mitchell JL, Ottridge RS, et al. Effectiveness of bariatric surgery vs community weight management intervention for the treatment of idiopathic intracranial hypertension: a randomized clinical trial. JAMA Neurol. 2021 Jun 1;78(6):678–686. doi: 10.1001/jamaneurol.2021.0659
  • Mollan SP, Mitchell JL, Yiangou A, et al. Association of Amount of weight Lost after bariatric surgery with intracranial pressure in women with idiopathic intracranial hypertension. Neurology. 2022 Sep 13;99(11):e1090–e1099. doi: 10.1212/WNL.0000000000200839
  • Mollan SP, Mytton J, Tsermoulas G, et al. Idiopathic intracranial hypertension: evaluation of admissions and emergency readmissions through the hospital episode statistic dataset between 2002–2020. Life. 2021 May 5;11(5):417. doi: 10.3390/life11050417
  • Adderley NJ, Subramanian A, Perrins M, et al. Headache, opiate use, and prescribing trends in women with idiopathic intracranial hypertension: a population-based matched cohort study. Neurology. 2022 Aug 19;99(18):e1968–78. doi: 10.1212/WNL.0000000000201064
  • Wall M, McDermott MP, Kieburtz KD, et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA. 2014 Apr 23-30;311(16):1641–1651. doi: 10.1001/jama.2014.3312
  • McCluskey G, Doherty-Allan R, McCarron P, et al. Meta-analysis and systematic review of population-based epidemiological studies in idiopathic intracranial hypertension. Eur J Neurol. 2018 Oct;25(10):1218–1227. doi: 10.1111/ene.13739
  • Markey K, Mitchell J, Botfield H, et al. 11β-hydroxysteroid dehydrogenase type 1 inhibition in idiopathic intracranial hypertension: a double-blind randomized controlled trial. Brain Commun. 2020;2(1):fcz050. doi: 10.1093/braincomms/fcz050
  • Mitchell JL, Lyons HS, Walker JK, et al. The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial. Brain. 2023 May 2;146(5):1821–1830. doi: 10.1093/brain/awad003
  • Lyons HS, Mollan SLP, Liu GT, et al. Different characteristics of pre-pubertal and post-pubertal idiopathic intracranial hypertension: a narrative review. Neuroophthalmology. 2023;47(2):63–74. doi: 10.1080/01658107.2022.2153874
  • Mollan SP, Chong YJ, Grech O, et al. Current perspectives on idiopathic intracranial hypertension without Papilloedema. Life. 2021 May 24;11(6):472. doi: 10.3390/life11060472
  • GA W, Wells G, Shea B, editors. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2014 https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
  • Gallezot JD, Nabulsi N, Henry S, et al. Imaging the enzyme 11β-hydroxysteroid dehydrogenase type 1 with PET: evaluation of the novel radiotracer (11)C-AS2471907 in human Brain. J Nucl Med. 2019 Aug;60(8):1140–1146. doi: 10.2967/jnumed.118.219766
  • Sinclair AJ, Onyimba CU, Khosla P, et al. Corticosteroids, 11beta-hydroxysteroid dehydrogenase isozymes and the rabbit choroid plexus. J Neuroendocrinol. 2007 Aug;19(8):614–620. doi: 10.1111/j.1365-2826.2007.01569.x
  • Veilleux A, Rhéaume C, Daris M, et al. Omental adipose tissue type 1 11 beta-hydroxysteroid dehydrogenase oxoreductase activity, body fat distribution, and metabolic alterations in women. J Clin Endocrinol Metab. 2009 Sep;94(9):3550–3557. doi: 10.1210/jc.2008-2011
  • Sandeep TC, Andrew R, Homer NZ, et al. Increased in vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone. Diabetes. 2005 Mar;54(3):872–879. doi: 10.2337/diabetes.54.3.872
  • Sinclair AJ, Walker EA, Burdon MA, et al. Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients with idiopathic intracranial hypertension: a link between 11beta-HSD1 and intracranial pressure regulation? J Clin Endocrinol Metab. 2010 Dec;95(12):5348–5356. doi: 10.1210/jc.2010-0729
  • Rauz S, Cheung CM, Wood PJ, et al. Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension. QJM. 2003 Jul;96(7):481–490. doi: 10.1093/qjmed/hcg085
  • Salpietro V, Polizzi A, Bertè LF, et al. Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis. Neuro Endocrinol Lett. 2012;33(6):569–573.
  • Boyle CD. Recent advances in the discovery of 11beta-HSD1 inhibitors. Curr Opin Drug Discovery Dev. 2008 Jul;11(4):495–511.
  • Hardy RS, Botfield H, Markey K, et al. 11βHSD1 inhibition with AZD4017 improves lipid profiles and lean muscle mass in idiopathic intracranial hypertension. J Clin Endocrinol Metab. 2020;106(1):174–187. doi: 10.1210/clinem/dgaa766
  • Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409–1439. doi: 10.1152/physrev.00034.2006
  • Botfield HF, Uldall MS, Westgate CSJ, et al. A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydrocephalus. Sci Transl Med. 2017 Aug 23:9(404). doi: 10.1126/scitranslmed.aan0972
  • Pollay M, Hisey B, Reynolds E, et al. Choroid plexus Na+/K±activated adenosine triphosphatase and cerebrospinal fluid formation. Neurosurgery. 1985 Nov;17(5):768–772. doi: 10.1227/00006123-198511000-00007
  • Lindvall-Axelsson M, Hedner P, Owman C. Corticosteroid action on choroid plexus: reduction in Na±K±ATPase activity, choline transport capacity, and rate of CSF formation. Exp Brain Res. 1989;77(3):605–610. doi: 10.1007/BF00249613
  • Lindvall-Axelsson M, Nilsson C, Owman C, et al. Inhibition of cerebrospinal fluid formation by omeprazole. Exp Neurol. 1992 Mar;115(3):394–399. doi: 10.1016/0014-4886(92)90204-4
  • Fisone G, Snyder GL, Fryckstedt J, et al. Na+,k(+)-ATPase in the choroid plexus. Regulation by serotonin/protein kinase C pathway. J Biol Chem. 1995 Feb 10;270(6):2427–2430. doi: 10.1074/jbc.270.6.2427
  • Han M-E, Kim H-J, Lee Y-S, et al. Regulation of cerebrospinal fluid production by caffeine consumption. BMC Neurosci. 2009 Sep 03;10(1):110. doi: 10.1186/1471-2202-10-110
  • Therien AG, Blostein R. Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol. 2000 Sep;279(3):C541–66. doi: 10.1152/ajpcell.2000.279.3.C541
  • Ferguson SS. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev. 2001 Mar;53(1):1–24.
  • Suzuki Y, Zhang H, Saito N, et al. Glucagon-like peptide 1 activates protein kinase C through Ca2±dependent activation of phospholipase C in insulin-secreting cells. J Biol Chem. 2006 Sep 29;281(39):28499–28507. doi: 10.1074/jbc.M604291200
  • Shigeto M, Kaku K. Are both protein kinase A- and protein kinase C-dependent pathways involved in glucagon-like peptide-1 action on pancreatic insulin secretion? J Diabetes Investig. 2014 Jul;5(4):347–348. doi: 10.1111/jdi.12225
  • Jones B, Sands C, Alexiadou K, et al. The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction. J Clin Endocrinol Metab. 2022 Jan 18;107(2):e767–e782. doi: 10.1210/clinem/dgab608
  • Abdeen G, le Roux CW. Mechanism underlying the weight loss and complications of Roux-en-Y gastric bypass. Rev Obes Surg. 2016 Feb;26(2):410–421. doi: 10.1007/s11695-015-1945-7
  • MJ AZ, Yiangou A, Yiangou A, et al. Determining the role of novel metabolic pathways in driving intracranial pressure reduction after weight loss. Brain Commun. 2023;5(5). doi: 10.1093/braincomms/fcad272
  • Mollan SP, Momin SNA, Khatkar PS, et al. A Neuro-Ophthalmologist’s Guide to Advances in Intracranial Pressure Measurements. Eye Brain. 2023 Dec 31;15(null):113–124. doi: 10.2147/EB.S404642
  • Wang JY, Wang QW, Yang XY, et al. GLP-1 receptor agonists for the treatment of obesity: role as a promising approach. Front Endocrinol. 2023;14:1085799. doi: 10.3389/fendo.2023.1085799
  • Fineman MS, Mace KF, Diamant M, et al. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diab Obes Metab. 2012 Jun;14(6):546–554. doi: 10.1111/j.1463-1326.2012.01561.x
  • Speake T, Whitwell C, Kajita H, et al. Mechanisms of CSF secretion by the choroid plexus. Microsc Res Tech. 2001 Jan 1;52(1):49–59. doi: 10.1002/1097-0029(20010101)52:1<49:AID-JEMT7>3.0.CO;2-C
  • Mollan SP, Fraser CL, Digre KB, et al. Guidelines of the International headache Society for controlled clinical trials in idiopathic intracranial hypertension. Cephalalgia. 2023 Aug;43(8):3331024231197118. doi: 10.1177/03331024231197118
  • Kobeissi H, Bilgin C, Ghozy S, et al. Common design and data elements reported on idiopathic intracranial hypertension trials: a systematic review. J Neuroophthalmol. 2023 Jun 21;Publish Ahead of Print. doi: 10.1097/WNO.0000000000001902
  • Mollan SP, Sinclair AJ. Outcomes measures in idiopathic intracranial hypertension. Expert Rev Neurother. 2021 Jun;21(6):687–700. doi: 10.1080/14737175.2021.1931127
  • Yiangou A, Mitchell JL, Fisher C, et al. Erenumab for headaches in idiopathic intracranial hypertension: a prospective open-label evaluation. Headache. 2021 Jan;61(1):157–169. doi: 10.1111/head.14026
  • Grech O, Seneviratne SY, Alimajstorovic Z, et al. Nuclear magnetic resonance spectroscopy metabolomics in idiopathic intracranial hypertension to identify markers of disease and headache. Neurology. 2022 Sep 8;99(16):e1702–14. doi: 10.1212/WNL.0000000000201007
  • Grech O, Clouter A, Mitchell JL, et al. Cognitive performance in idiopathic intracranial hypertension and relevance of intracranial pressure. Brain Commun. 2021 Sep 2;3(3):fcab202. doi: 10.1093/braincomms/fcab202

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.