Translational impact of basic science promotes a new era of precision medicine for migraine
Abstract Precision medicine has emerged as a powerful approach to improve treatment outcomes for many medical conditions by consideration of the genetic characteristics of the patient. Migraine is likely to be the world’s most common neurological disorder affecting over 1 billion people, approximately 700 million of whom are women. Yet, patient sex, the most basic genetic difference, is rarely considered in selection of therapies for people with migraine. Preclinical studies reveal that calcitonin gene-related peptide (CGRP), a neurotransmitter thought to be causal in promoting migraine in many patients, elicits female selective pain and headache-like responses. Consistent with this, we report a subgroup analysis of publicly available clinical data evaluating small molecule CGRP receptor antagonists for the acute migraine revealing preferential efficacy in women. Analyses of human post-mortem sensory neurons from male and female donors reveal sexual dimorphism at transcript, protein and functional levels. These findings raise the possibility that regardless of common diagnosis and phenotype, mechanisms promoting migraine pain may differ between sexes. Such qualitative sex differences suggest that clinical trials should include sex-specific analyses, that sex stratified treatment guidelines may improve treatment outcomes in migraine and that the uniform therapeutic approach to pain-related disorders in men and women requires reassessment..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 31. Juli Zur Gesamtaufnahme - year:2023 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Porreca, Frank [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2023.07.25.23293169 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI040353214 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI040353214 | ||
| 003 | DE-627 | ||
| 005 | 20230801090233.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230729s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2023.07.25.23293169 |2 doi | |
| 035 | |a (DE-627)XBI040353214 | ||
| 035 | |a (biorXiv)10.1101/2023.07.25.23293169 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Porreca, Frank |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Translational impact of basic science promotes a new era of precision medicine for migraine |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Precision medicine has emerged as a powerful approach to improve treatment outcomes for many medical conditions by consideration of the genetic characteristics of the patient. Migraine is likely to be the world’s most common neurological disorder affecting over 1 billion people, approximately 700 million of whom are women. Yet, patient sex, the most basic genetic difference, is rarely considered in selection of therapies for people with migraine. Preclinical studies reveal that calcitonin gene-related peptide (CGRP), a neurotransmitter thought to be causal in promoting migraine in many patients, elicits female selective pain and headache-like responses. Consistent with this, we report a subgroup analysis of publicly available clinical data evaluating small molecule CGRP receptor antagonists for the acute migraine revealing preferential efficacy in women. Analyses of human post-mortem sensory neurons from male and female donors reveal sexual dimorphism at transcript, protein and functional levels. These findings raise the possibility that regardless of common diagnosis and phenotype, mechanisms promoting migraine pain may differ between sexes. Such qualitative sex differences suggest that clinical trials should include sex-specific analyses, that sex stratified treatment guidelines may improve treatment outcomes in migraine and that the uniform therapeutic approach to pain-related disorders in men and women requires reassessment. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Navratilova, Edita |4 aut | |
| 700 | 1 | |a Hirman, Joe |4 aut | |
| 700 | 1 | |a MaassenVanDenBrink, Antoinette |4 aut | |
| 700 | 1 | |a Lipton, Richard B. |4 aut | |
| 700 | 1 | |a Dodick, David W. |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 31. Juli |
| 773 | 1 | 8 | |g year:2023 |g day:31 |g month:07 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2023.07.25.23293169 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 31 |c 07 | ||