Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

Clinical Autonomic Research - In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective...     

Pharmacokinetics and pharmacodynamics of ampreloxetine,a novel,selective norepinephrine reuptake inhibitor,in symptomatic neurogenic orthostatic hypotension

Clinical Autonomic Research - Ampreloxetine is a novel, selective, long-acting norepinephrine reuptake (NET) inhibitor being investigated as a once-daily oral treatment for symptomatic neurogenic...     

Response to: Human papillomavirus (HPV) vaccine safety concerning POTS,CRPS and related conditions

Clinical Autonomic Research -     

Usefulness of tilt-induced heart rate changes in the differential diagnosis of vasovagal syncope and chronic autonomic failure

Objective  

To determine whether the heart rate changes during tilt table testing could be used in the differential diagnosis between vasovagal syncope and chronic autonomic failure.     

Improvement of daytime hypercapnia with nocturnal non-invasive ventilation in familial dysautonomia

Clinical Autonomic Research -     

Kinetin improves IKBKAP mRNA splicing in patients with familial dysautonomia

Familial dysautonomia (FD) is caused by an intronic splice mutation in the IKBKAP gene that leads to partial skipping of exon 20 and tissue-specific reduction in I-κ-B kinase complex-associated protein/elongation protein 1 (IKAP/ELP-1) expression. Kinetin (6-furfurylaminopurine) has been shown to improve splicing and increase WT IKBKAP mRNA and IKAP protein expression in FD cell lines and carriers. To determine whether oral kinetin treatment could alter mRNA splicing in FD subjects and was tolerable, we administered kinetin to eight FD individuals homozygous for the splice mutation. Subjects received 23.5 mg/Kg/d for 28 d. An increase in WT IKBKAP mRNA expression in leukocytes was noted after 8 d in six of eight individuals; after 28 d, the mean increase compared with baseline was significant (p = 0.002). We have demonstrated that kinetin is tolerable in this medically fragile population. Not only did kinetin produce the desired effect on splicing in FD patients but also that effect seems to improve with time despite lack of dose change. This is the first report of a drug that produces in vivo mRNA splicing changes in individuals with FD and supports future long-term trials to determine whether kinetin will prove therapeutic in FD patients.     

Impact of depressive symptoms on self-perceived severity of autonomic dysfunction in multiple system atrophy: relevance for patient-reported outcomes in clinical trials

Clinical Autonomic Research - To assess the relationship between depressive symptoms and self-perceived severity of autonomic dysfunction in patients with multiple system atrophy (MSA)....