Efficacy of galcanezumab in proline-rich transmembrane protein 2 (PRRT2)-associated familial hemiplegic migraine: A case series

Costanza Sottani; Giulia Di Lazzaro; Paolo Calabresi; Maria Grazia Pomponi; Francesco Danilo Tiziano; Anna Rita Bentivoglio; Serenella Servidei; Catello Vollono

doi:10.1111/head.14840

Efficacy of galcanezumab in proline-rich transmembrane protein 2 (PRRT2)-associated familial hemiplegic migraine: A case series

Headache. 2024 Sep 30. doi: 10.1111/head.14840. Online ahead of print.

Authors

Costanza Sottani¹, Giulia Di Lazzaro^{1

2}, Paolo Calabresi^{1

2}, Maria Grazia Pomponi³, Francesco Danilo Tiziano^{3

4}, Anna Rita Bentivoglio^{1

2}, Serenella Servidei^{1

5}, Catello Vollono^{1

5}

Affiliations

¹ Neurology Section, Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
² UOC Neurologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
³ UOC Genetica Medica, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
⁴ Section of Genomic Medicine, Department of Public Health and Life Sciences, Università Cattolica del Sacro Cuore, Rome, Italy.
⁵ UOC Neurofisiopatologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

PMID: 39345003
DOI: 10.1111/head.14840

Abstract

Background: Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura. Variants in calcium voltage-gated channel subunit alpha1 A (CACNA1A), ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2), and sodium voltage-gated channel alpha subunit 1 (SCN1A) genes have a well-established association with the development of FHM. Recent studies suggest that other genes may also have a significant role in the pathogenesis of FHM, including proline-rich transmembrane protein 2 (PRRT2). To our knowledge, there are currently no documented reports of the use of monoclonal antibodies targeting calcitonin gene-related peptide in FHM caused by a specific identified genetic mutation - and in particular not in FHM associated with PRRT2 mutations. The aim of our work is to describe the efficacy of galcanezumab as a prophylaxis treatment on patients from an Italian family consisting of six patient carriers of a PRRT2 pathogenic variant.

Methods: Inclusion criteria for treatment eligibility consisted of a confirmed diagnosis of genetically confirmed FHM as defined by the International Classification of Headache Disorders, third edition, number of headache days/month ≥4, and at least two previously failed migraine prophylaxis treatments. We evaluated clinical data of patients treated with galcanezumab regarding number of headache days/month, frequency of aura, disability caused by HM using the Migraine Disability Assessment (MIDAS), attack severity through a numerical rating scale (NRS), acute medications intake, and response to acute medications at baseline (t0) and after 3 (t1) and 6 (t2) months of treatment.

Results: Three out of six family members met inclusion criteria for treatment with galcanezumab. The average number of headache days/month, acute medications, and MIDAS significantly decreased in all treated patients, as well as the average NRS score. Aura frequency reduced by ≥50% compared to the baseline in all three patients. No adverse events related to galcanezumab were reported.

Conclusion: Galcanezumab is a valid and well-tolerated treatment option in PRRT2-associated FHM.

Keywords: calcitonin gene‐related peptide; galcanezumab; hemiplegic familial migraine; proline‐rich transmembrane protein 2.