RARE DISEASE
Ehlers-Danlos syndrome
Ehlers-Danlos syndrome
Ehlers-Danlos syndrome
Synonyms: EDS
Synonyms: EDS
Synonyms: EDS
Drug discovery
3
drugs
With orphan designations
Overview
Ehlers-Danlos syndrome (EDS) comprises 13 heritable connective tissue disorders characterized by collagen defects, leading to joint hypermobility, skin fragility, chronic pain, and multisystem involvement (e.g., cardiovascular, gastrointestinal, autonomic dysfunction). The hypermobile type (hEDS) is most common. Diagnosis relies on clinical criteria and genetic testing (except hEDS). Management focuses on symptom mitigation and musculoskeletal stabilization [1][6][15].
Burden
Therapies
Physical/occupational therapy: Joint stabilization, low-impact exercise, and adaptive devices [3][16].
Pain management: NSAIDs, neuromodulators (e.g., gabapentin), and non-pharmacological approaches (e.g., warm baths, TENS) [3][8][13].
Multidisciplinary care: Includes POTS/dysautonomia management, cognitive behavioral therapy, and genetic counseling [5][16].
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare skin diseases, rare systemic and rheumatological diseases
Research Papers
760 drug discovery papers about Ehlers-Danlos syndrome, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
760 drug discovery papers about Ehlers-Danlos syndrome, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-08 | Excessive Hypocapnic Cerebral Vasoconstriction in Hypermobile Ehlers-Danlos Syndrome Assessed With Real-Time Magnetic Resonance Imaging During Lower-Body Negative Pressure.
Orthostatic intolerance is common in hypermobile Ehlers-Danlos syndrome (hEDS) with one third of patients fulfilling postural orthostatic tachycardia syndrome criteria. Our aim was to assess cerebral blood flow in patients with hEDS and postural orthostatic tachycardia syndrome during orthostasis, which may be responsible for orthostatic intolerance. In 18 individuals with hEDS and postural orthostatic tachycardia syndrome and 20 healthy controls, we conducted real-time phase contrast magnetic resonance imaging of the middle cerebral artery with and without an orthostatic challenge through 30 mm Hg lower-body negative pressure. During lower-body negative pressure, heart rate increased more in hEDS than in controls (15.0±8.3 bpm versus 7.8±7.7 bpm, P=0.009); blood pressure remained unchanged; middle cerebral artery flow per heartbeat decreased more in hEDS (-28%±16% versus -15%±13% in controls, P=0.013) with decreased mean volumetric flow in hEDS (-12%±17%, P<0.001 versus -6%±8% in controls, P=0.102); average middle cerebral artery peak blood flow velocity decreased in both groups (hEDS: 44.6±8.1 cm/s to 37.6±8.4 cm/s, P<0.001; controls: 40.3±10.9 cm/s to 36.9±11.1 cm/s, P=0.018); respiration rate increased in hEDS (14.3±5.1/min to 17.4±5.3/min, P=0.002) leading to a decrease in end-tidal CO2 (39.2±4.2 mm Hg to 35.6±6.4 mm Hg, P=0.025), and cerebrovascular resistance increased more in hEDS (50.8%±48.4%, P<0.001) versus (20.3%±20.6%, P=0.005) in controls. Individuals with hEDS and postural orthostatic tachycardia syndrome maintain cerebral perfusion primarily through tachycardic compensation during orthostatic stress despite hypocapnic vasoconstriction. URL: https://drks.de/search/en; Unique Identifier: DRKS00028279.
2026-06-17 | Ciprofloxacin Exposure Promotes Aortic Dissection and Arterial Rupture in a Mouse Model of Vascular Ehlers-Danlos Syndrome.
We tested the hypothesis that ciprofloxacin exposure increases the incidence of aortic dissection and arterial rupture in vEDS mice. While data support that fluoroquinolones exacerbate lethal sequela in some types of aortic pathology, the potential danger of these drugs has not been studied in the context of vascular Ehlers-Danlos syndrome (vEDS). Eight-week-old male and female vEDS mice (Col3a1[G209S/WT]) and wild-type littermates (Col3a1[WT/WT]) were randomly assigned to receive either ciprofloxacin (n=25) or vehicle control (n=24) through daily gavage for 2 weeks and were monitored for 4 weeks. We compared groups based on survival, aortic dissection and rupture incidence, and aortic tissue levels of collagen, lysyl oxidase (LOX), matrix metalloproteinases (MMP), macrophages, and apoptosis. All vEDS mice that received vehicle and all littermate controls survived the 4-week study period. In contrast, 44% of vEDS mice that received ciprofloxacin died (P<0.001) due to aortic or arterial rupture manifesting as hemopericardium or hemothorax, most within 7 days of exposure. Findings were similar in male and female vEDS mice. Compared to aortic tissue from vehicle-treated vEDS mice, tissue from ciprofloxacin-treated vEDS mice exhibited decreased collagen content, decreased LOX, increased MMP 2 and 9 levels, increased macrophage infiltration, and increased apoptosis (all P<0.001). In a mouse model of vEDS, ciprofloxacin exposure resulted in aortic inflammation, collagen disruption, cell death, reduced LOX, and increased risk of fatal dissection and rupture of the aorta and branch arteries. These novel translational findings strongly support recommendations to avoid fluoroquinolones in patients with vEDS.
2026-05-26 | Too high and too loose: dysautonomia and the hypertensive paradox in hypermobility disorders.
Hypertension in hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) represents an increasingly recognized but poorly understood clinical phenomenon. This review addresses the unique pathophysiology, diagnostic considerations, and management challenges of hypertension occurring in the context of dysautonomia - a comorbidity affecting up to 70% of patients with hEDS/HSD. Emerging evidence identifies distinct hypertensive endotypes in hEDS/HSD, including hyperadrenergic dysautonomia, paroxysmal hypertension, cervicogenic hypertension, and nocturnal/supine hypertension. Pathophysiologic mechanisms involve connective tissue laxity, altered baroreflex function, small fiber neuropathy, and mast cell activation. Standard antihypertensive therapies may paradoxically worsen symptoms by exacerbating orthostatic intolerance, while targeted approaches using alpha-blockers and central sympatholytics show promise in hyperadrenergic phenotypes. Management of hypertension in hEDS/HSD requires adaptation of standard guidelines to accommodate dysautonomia-specific considerations, including withdrawal of provocative medications, avoidance of volume-depleting agents, and phenotype-directed pharmacotherapy. Long-term cardiovascular outcomes remain poorly defined, highlighting critical research gaps and the need for evidence-based consensus guidelines tailored to this unique patient population.
2026-04-28 | Outpatient buprenorphine micro-induction for an older adult with chronic pain and opioid use disorder: a case report.
Buprenorphine micro-induction enables a gradual transition from full opioid agonists without requiring abstinence, minimizing the risk of precipitated withdrawal. This approach is particularly beneficial for older adults with chronic pain who remain on long-term opioid therapy and may be reluctant or medically unfit to undergo traditional induction protocols. A 68-year-old woman with Ehlers-Danlos Syndrome, complex surgical history, and severe opioid use disorder who was taking 280 (Morphine Milligram Equivalents per Day), including prescribed morphine and illicit hydromorphone. She underwent an outpatient buprenorphine-naloxone micro-induction while continuing full agonist use until target dose was reached. Doses were titrated over seven days with minimal withdrawal symptoms. She successfully transitioned to buprenorphine-naloxone 4-1 mg QID (Four Times Per Day), reporting improved pain, mobility, and overall functioning. Outpatient micro-induction can be safely implemented in older adults with chronic opioid exposure, particularly those receiving prescription opioids from outside prescribers for chronic pain. This case underscores the utility of pharmacogenomics, trauma-informed care, and interdisciplinary coordination to facilitate successful transition to MOUD.
2026-04-28 | Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome.
Aortic dissection or rupture is a leading cause of mortality in vascular Ehlers-Danlos syndrome (VEDS), a disorder caused by mutations in the COL3A1 gene. Col3a1G938D/+ mice recapitulate features of VEDS, including high risk of aortic rupture. As in people with VEDS, aortic risk in this model accelerates at the onset of puberty, especially in males. We identify developmentally regulated gene programs associated with this vulnerability and that are targeted by treatments that mitigate aortic risk. Both genetic and pharmacological inhibition of the androgen receptor (AR) eliminated survival differences between sexes, while treatment with a dual AR and mineralocorticoid receptor (MR) antagonist provided near-complete and durable protection in both sexes. Pathways targeted by dual AR/MR inhibition, including those related to extracellular matrix (ECM) organization and cell-ECM interactions, largely overlapped with those also modulated by isolated MR antagonism. Selective targeting of MR signaling emerged as an effective therapeutic strategy in both sexes that avoids sexual side effects in males.
2026-08-08 | Excessive Hypocapnic Cerebral Vasoconstriction in Hypermobile Ehlers-Danlos Syndrome Assessed With Real-Time Magnetic Resonance Imaging During Lower-Body Negative Pressure.
Orthostatic intolerance is common in hypermobile Ehlers-Danlos syndrome (hEDS) with one third of patients fulfilling postural orthostatic tachycardia syndrome criteria. Our aim was to assess cerebral blood flow in patients with hEDS and postural orthostatic tachycardia syndrome during orthostasis, which may be responsible for orthostatic intolerance. In 18 individuals with hEDS and postural orthostatic tachycardia syndrome and 20 healthy controls, we conducted real-time phase contrast magnetic resonance imaging of the middle cerebral artery with and without an orthostatic challenge through 30 mm Hg lower-body negative pressure. During lower-body negative pressure, heart rate increased more in hEDS than in controls (15.0±8.3 bpm versus 7.8±7.7 bpm, P=0.009); blood pressure remained unchanged; middle cerebral artery flow per heartbeat decreased more in hEDS (-28%±16% versus -15%±13% in controls, P=0.013) with decreased mean volumetric flow in hEDS (-12%±17%, P<0.001 versus -6%±8% in controls, P=0.102); average middle cerebral artery peak blood flow velocity decreased in both groups (hEDS: 44.6±8.1 cm/s to 37.6±8.4 cm/s, P<0.001; controls: 40.3±10.9 cm/s to 36.9±11.1 cm/s, P=0.018); respiration rate increased in hEDS (14.3±5.1/min to 17.4±5.3/min, P=0.002) leading to a decrease in end-tidal CO2 (39.2±4.2 mm Hg to 35.6±6.4 mm Hg, P=0.025), and cerebrovascular resistance increased more in hEDS (50.8%±48.4%, P<0.001) versus (20.3%±20.6%, P=0.005) in controls. Individuals with hEDS and postural orthostatic tachycardia syndrome maintain cerebral perfusion primarily through tachycardic compensation during orthostatic stress despite hypocapnic vasoconstriction. URL: https://drks.de/search/en; Unique Identifier: DRKS00028279.
2026-06-17 | Ciprofloxacin Exposure Promotes Aortic Dissection and Arterial Rupture in a Mouse Model of Vascular Ehlers-Danlos Syndrome.
We tested the hypothesis that ciprofloxacin exposure increases the incidence of aortic dissection and arterial rupture in vEDS mice. While data support that fluoroquinolones exacerbate lethal sequela in some types of aortic pathology, the potential danger of these drugs has not been studied in the context of vascular Ehlers-Danlos syndrome (vEDS). Eight-week-old male and female vEDS mice (Col3a1[G209S/WT]) and wild-type littermates (Col3a1[WT/WT]) were randomly assigned to receive either ciprofloxacin (n=25) or vehicle control (n=24) through daily gavage for 2 weeks and were monitored for 4 weeks. We compared groups based on survival, aortic dissection and rupture incidence, and aortic tissue levels of collagen, lysyl oxidase (LOX), matrix metalloproteinases (MMP), macrophages, and apoptosis. All vEDS mice that received vehicle and all littermate controls survived the 4-week study period. In contrast, 44% of vEDS mice that received ciprofloxacin died (P<0.001) due to aortic or arterial rupture manifesting as hemopericardium or hemothorax, most within 7 days of exposure. Findings were similar in male and female vEDS mice. Compared to aortic tissue from vehicle-treated vEDS mice, tissue from ciprofloxacin-treated vEDS mice exhibited decreased collagen content, decreased LOX, increased MMP 2 and 9 levels, increased macrophage infiltration, and increased apoptosis (all P<0.001). In a mouse model of vEDS, ciprofloxacin exposure resulted in aortic inflammation, collagen disruption, cell death, reduced LOX, and increased risk of fatal dissection and rupture of the aorta and branch arteries. These novel translational findings strongly support recommendations to avoid fluoroquinolones in patients with vEDS.
2026-05-26 | Too high and too loose: dysautonomia and the hypertensive paradox in hypermobility disorders.
Hypertension in hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) represents an increasingly recognized but poorly understood clinical phenomenon. This review addresses the unique pathophysiology, diagnostic considerations, and management challenges of hypertension occurring in the context of dysautonomia - a comorbidity affecting up to 70% of patients with hEDS/HSD. Emerging evidence identifies distinct hypertensive endotypes in hEDS/HSD, including hyperadrenergic dysautonomia, paroxysmal hypertension, cervicogenic hypertension, and nocturnal/supine hypertension. Pathophysiologic mechanisms involve connective tissue laxity, altered baroreflex function, small fiber neuropathy, and mast cell activation. Standard antihypertensive therapies may paradoxically worsen symptoms by exacerbating orthostatic intolerance, while targeted approaches using alpha-blockers and central sympatholytics show promise in hyperadrenergic phenotypes. Management of hypertension in hEDS/HSD requires adaptation of standard guidelines to accommodate dysautonomia-specific considerations, including withdrawal of provocative medications, avoidance of volume-depleting agents, and phenotype-directed pharmacotherapy. Long-term cardiovascular outcomes remain poorly defined, highlighting critical research gaps and the need for evidence-based consensus guidelines tailored to this unique patient population.
2026-04-28 | Outpatient buprenorphine micro-induction for an older adult with chronic pain and opioid use disorder: a case report.
Buprenorphine micro-induction enables a gradual transition from full opioid agonists without requiring abstinence, minimizing the risk of precipitated withdrawal. This approach is particularly beneficial for older adults with chronic pain who remain on long-term opioid therapy and may be reluctant or medically unfit to undergo traditional induction protocols. A 68-year-old woman with Ehlers-Danlos Syndrome, complex surgical history, and severe opioid use disorder who was taking 280 (Morphine Milligram Equivalents per Day), including prescribed morphine and illicit hydromorphone. She underwent an outpatient buprenorphine-naloxone micro-induction while continuing full agonist use until target dose was reached. Doses were titrated over seven days with minimal withdrawal symptoms. She successfully transitioned to buprenorphine-naloxone 4-1 mg QID (Four Times Per Day), reporting improved pain, mobility, and overall functioning. Outpatient micro-induction can be safely implemented in older adults with chronic opioid exposure, particularly those receiving prescription opioids from outside prescribers for chronic pain. This case underscores the utility of pharmacogenomics, trauma-informed care, and interdisciplinary coordination to facilitate successful transition to MOUD.
2026-04-28 | Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome.
Aortic dissection or rupture is a leading cause of mortality in vascular Ehlers-Danlos syndrome (VEDS), a disorder caused by mutations in the COL3A1 gene. Col3a1G938D/+ mice recapitulate features of VEDS, including high risk of aortic rupture. As in people with VEDS, aortic risk in this model accelerates at the onset of puberty, especially in males. We identify developmentally regulated gene programs associated with this vulnerability and that are targeted by treatments that mitigate aortic risk. Both genetic and pharmacological inhibition of the androgen receptor (AR) eliminated survival differences between sexes, while treatment with a dual AR and mineralocorticoid receptor (MR) antagonist provided near-complete and durable protection in both sexes. Pathways targeted by dual AR/MR inhibition, including those related to extracellular matrix (ECM) organization and cell-ECM interactions, largely overlapped with those also modulated by isolated MR antagonism. Selective targeting of MR signaling emerged as an effective therapeutic strategy in both sexes that avoids sexual side effects in males.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
3 orphan drug designations for Ehlers-Danlos syndrome.
3 orphan drug designations for Ehlers-Danlos syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Enzastaurin hydrochloride | small molecules | EMA | 2022-02-24 | — | Orphix Consulting GmbH |
enzastaurin | small molecules | FDA | 2021-12-07 | — | Aytu BioPharma, Inc. |
celiprolol | small molecules | FDA | 2015-01-05 | — | Acer Therapeutics, Inc. |
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