Faculty Bibliography
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342
Autoantibodies blocking M3 muscarinic receptors cause postganglionic cholinergic dysautonomia
A 10-year-old girl presented with ileus, urinary retention, dry mouth, lack of tears, fixed dilated pupils, and diffuse anhidrosis 7-days after a febrile illness. We hypothesized that her syndrome was due to autoimmunity against muscarinic acetylcholine receptors, blocking their activation. Using an indirect enzyme-linked immunosorbent assay for all five muscarinic receptors (M1 -M5 ) we identified in the patient's serum antibodies that selectively bound to M3 receptors. In-vitro functional studies confirmed that these autoantibodies selectively blocked M3 receptor activation. Thus, autoantibodies against M3 acetylcholine receptors can cause acute postganglionic cholinergic dysautonomia. This article is protected by copyright. All rights reserved.
PMID: 32833276
ISSN: 1531-8249
CID: 4583782
Cerebellar and parkinsonian phenotypes of multiple system atrophy: differences and similarities at baseline from the Natural History Study of the Synucleinopathies [Meeting Abstract]
ISI:000536058008260
ISSN: 0028-3878
CID: 4561832
Differences and Similarities Between the Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease in the Natural History Study of the Synucleinopathies [Meeting Abstract]
ISI:000536058008079
ISSN: 0028-3878
CID: 4561812
Effects of Once-Daily Ampreloxetine (TD-9855), a Norepinephrine Reuptake Inhibitor, on Blood Pressure in Subjects With Symptomatic Neurogenic Orthostatic Hypotension [Meeting Abstract]
ISI:000536058001177
ISSN: 0028-3878
CID: 4561132
An Open-Label Phase 2 Study to Explore the Durability of Effect, and Safety of Once-Daily Oral Ampreloxetine (TD-9855), a Norepinephrine Reuptake Inhibitor, for the Symptomatic Treatment of Neurogenic Orthostatic Hypotension in Subjects With Synucleinopathies [Meeting Abstract]
ISI:000536058001166
ISSN: 0028-3878
CID: 4561122
Cutaneous Alpha-Synuclein Deposition Across the Synucleinopathies [Meeting Abstract]
ISI:000536058003261
ISSN: 0028-3878
CID: 4561362
Nerve Conduction Studies in Familial Dysautonomia [Meeting Abstract]
ISI:000536058007226
ISSN: 0028-3878
CID: 4561762
Presentation, Causes, and Hemodynamic Features of Acquired Afferent Baroreflex Failure [Meeting Abstract]
ISI:000536058007136
ISSN: 0028-3878
CID: 4561712
Anticipatory Autonomic responses in Patients with Postural Tachycardia Syndrome [Meeting Abstract]
ISI:000536058007250
ISSN: 0028-3878
CID: 4561782
Effects of Once-Daily Ampreloxetine (TD- 9855), a Norepinephrine Reuptake Inhibitor, on Blood Pressure in Subjects With Symptomatic Neurogenic Orthostatic Hypotension Associated With Synucleinopathies [Meeting Abstract]
Background and aims: In neurogenic orthostatic hypotension (nOH), standing blood pressure (BP) falls due to inadequate norepinephrine (NE) release. Ampreloxetine, a novel, long-acting, NE reuptake inhibitor, has shown durable symptom improvement in subjects with nOH associated with synucleinopathies. The objective of this study was to evaluate BP regulation in subjects with symptomatic nOH treated with open-label ampreloxetine.
Method(s): In a phase 2 study, subjects received ampreloxetine once-daily (3-20mg) for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 score (OHSA#1; dizziness, lightheadedness, feeling faint); standing/sitting/supine systolic BP (SBP); standing duration; and plasma NE.
Result(s): 17 symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). Mean increase in 3-minute standing SBP from baseline at Weeks 4 and 20 was 9.0mmHg and 10.8mmHg, respectively; >50% of subjects maintained SBP >80mmHg. Sitting SBP changes were less, with little change in supine SBP. At Week 4, 67% of subjects could stand for >5 mins, 31% improvement from baseline. NE plasma levels rose from pre-dose to Week 4 (1664.93-2231.67pmol/l). Baseline NE plasma levels correlated with standing BP increase. Ampreloxetine was well tolerated. Durable symptom improvement in nOH was accompanied by increase in standing and sitting SBP, standing duration, and NE plasma levels, with little effect on supine SBP.
Conclusion(s): These encouraging findings on BP regulation in nOH with ampreloxetine treatment for up to 5 months are being evaluated in ongoing Phase 3, double-blind, confirmatory studies in subjects with nOH
Method(s): In a phase 2 study, subjects received ampreloxetine once-daily (3-20mg) for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 score (OHSA#1; dizziness, lightheadedness, feeling faint); standing/sitting/supine systolic BP (SBP); standing duration; and plasma NE.
Result(s): 17 symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). Mean increase in 3-minute standing SBP from baseline at Weeks 4 and 20 was 9.0mmHg and 10.8mmHg, respectively; >50% of subjects maintained SBP >80mmHg. Sitting SBP changes were less, with little change in supine SBP. At Week 4, 67% of subjects could stand for >5 mins, 31% improvement from baseline. NE plasma levels rose from pre-dose to Week 4 (1664.93-2231.67pmol/l). Baseline NE plasma levels correlated with standing BP increase. Ampreloxetine was well tolerated. Durable symptom improvement in nOH was accompanied by increase in standing and sitting SBP, standing duration, and NE plasma levels, with little effect on supine SBP.
Conclusion(s): These encouraging findings on BP regulation in nOH with ampreloxetine treatment for up to 5 months are being evaluated in ongoing Phase 3, double-blind, confirmatory studies in subjects with nOH
EMBASE:632534545
ISSN: 1468-1331
CID: 4558242
