This RDCRC on Rare Autonomic Diseases encompasses 5 major centers: Vanderbilt University, Mayo/Rochester, New York University, Beth Israel Deaconess/Harvard, and the NINDS/Clinical Center. Major support groups for autonomic disorders are engaged and participate. During the renewal period, our research efforts will focus on the rare autonomic diseases of multiple system atrophy (MSA), pure autonomic failure (PAF), and hyperadrenergic postural tachycardia syndrome (POTS), as well as dementia with Lewy bodies and other synucleinopathies. The overall objectives of our Consortium are to improve our understanding of the pathophysiology of these diseases to develop novel therapies to not only alleviate patients' symptoms but also to intervene in disease progression, and hopefully when possible to find a cure. Over the past four years, we met virtually all specific goals of our initial funding cycle. We developed a website that educates patients, researchers and clinicians, and assists with recruitment for the various consortium studies. We enrolled 469 patients in the ongoing natural history study of neurogenic orthostatic hypotension (and a total of 656 in all projects). We met target enrollment ahead of schedule in a randomized, double-blind, placebo-controlled trial of rifampicin in patients with MSA. While rifampicin did not improve MSA, this study taught us much, providing valuable insights and strategies that have been incorporated into the design of the clinical projects in our renewal. We also completed enrollment in a proof-of-concept study to examine the role of norepinephrine reuptake blockade as both a diagnostic and therapeutic tool in patients with neurogenic orthostatic hypotension. For this renewal, in addition to continuing with an expanded phenotyping and natural history study, we propose three new clinical projects and three new pilot projects. A trial of mesenchymal stem cells is directed at combating the growth factor deficiency recently identified in MSA. Our studies suggest that atomoxetine can improve orthostatic tolerance. We are proposing similar studies with reducing splanchnic capacitance in neurogenic orthostatic hypotension, harnessing residual sympathetic tone with 3,4- diaminopyridine in MSA and a novel vagal stimulation strategy in hyperadrenergic POTS. These studies will be linked with efforts to expand our development of autonomic biomarkers. Continuation of the Autonomic RDCRC will enable us to build on our recent new knowledge to understand and hopefully alter the course of these diseases. We will work collaboratively with patient advocacy groups. We will address informative biomarkers and elucidate mechanisms to find genuinely effective agents for the rare autonomic diseases.
Autonomic disorders cause loss of regulation of the heart, blood vessels, stomach, bowel and bladder. Affected patients frequently have palpitations or lose consciousness, and some have a rapidly fatal course. The Autonomic Consortium proposes to join with patient support groups to harness the knowledge and energies of physicians and investigators in the major centers where these patients are cared for, so that they can discover ways to treat and to cure these diseases.
| Ogaki, Kotaro; Martens, Yuka A; Heckman, Michael G et al. (2018) Multiple system atrophy and apolipoprotein E. Mov Disord 33:647-650 |
| Palma, Jose-Alberto; Spalink, Christy; Barnes, Erin P et al. (2018) Neurogenic dysphagia with undigested macaroni and megaesophagus in familial dysautonomia. Clin Auton Res 28:125-126 |
| Singh, Kanwaljit; Palma, Jose-Alberto; Kaufmann, Horacio et al. (2018) Prevalence and characteristics of sleep-disordered breathing in familial dysautonomia. Sleep Med 45:33-38 |
| Norcliffe-Kaufmann, Lucy; Galindo-Mendez, Brahyan; Garcia-Guarniz, Ana-Lucia et al. (2018) Transcranial Doppler in autonomic testing: standards and clinical applications. Clin Auton Res 28:187-202 |
| Mehr, Shahram E; Barbul, Adrian; Shibao, Cyndya A (2018) Gastrointestinal symptoms in postural tachycardia syndrome: a systematic review. Clin Auton Res 28:411-421 |
| Wenning, Gregor; Trojanowski, John Q; Kaufmann, Horacio et al. (2018) Is multiple system atrophy an infectious disease? Ann Neurol 83:10-12 |
| Cutsforth-Gregory, Jeremy K; McKeon, Andrew; Coon, Elizabeth A et al. (2018) Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure. Mayo Clin Proc 93:1440-1447 |
| Palma, Jose-Alberto (2018) Autonomic dysfunction in Parkinson's disease and other synucleinopathies: Introduction to the series. Mov Disord 33:347-348 |
| van den Berg, Maarten P; Almomani, Rowida; Biaggioni, Italo et al. (2018) Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. Circ Res 122:846-854 |
| Bar-Aluma, Bat-El; Efrati, Ori; Kaufmann, Horacio et al. (2018) A Controlled Trial of Inhaled Bronchodilators in Familial Dysautonomia. Lung 196:93-101 |
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