project 1 - Autonomic Rare Diseases Clinical Research Consortium

  • Low, Phillip Anson (PI)
  • Goldstein, D. (PI)
  • Freeman, R.O.Y. (PI)
  • Kaufmann, Horacio (PI)
  • Freeman, R.O.Y. (PI)
  • Goldstein, D. (PI)
  • Robertson, David Herlie (PI)
  • Biaggioni, Italo (PI)

Project: Research project


JECT 1 NYU PROJECT SUMMARY (See instructions):
Pure autonomic failure (PAF) is a neurodegenerative disorder characterized clinically by orthostatic
hypotension (OH) and pathologically by intracellular deposits of the protein alpha synuclein. As in Parkinson
disease (PD), in PAF alpha synuclein aggregates in neuronal cytoplasmic inclusions called Lewy bodies
(LBs). LB in PAF are numerous in peripheral autonomic neurons with only a few in the substantia nigra and
scattered in the CNS. PAF is one of three LB disorders, a category that includes PD and dementia with Lewy
bodies (DLB). Each of these disorders affects different neuronal groups relatively selectively, resulting in
distinct but overlapping autonomic, motor, and cognitive phenotypes. Because of paucity of data on the
natural history of PAF, however, it is not known whether the striatum and other cortical areas remain intact in
PAF over time. Specific Aim 1 of this project is to conduct a prospective, longitudinal study to define the
natural history of PAF and determine whether the disease remains confined to autonomic neurons or
develops eventually into one of the other LB disorders, i.e., PD or DLB. If PAF patients sustain the "pure"
autonomic phenotype, PAF might entail neuroprotective features that prevent the disorder from spreading to
the brain affecting motor and cognitive function. Understanding the mechanisms of this neuroprotection
could aid in the development of treatments for all LB disorders. The characteristic clinical manifestation of
PAF, neurogenic orthostatic hypotension, can also be the initial manifestation of multiple system atrophy
(MSA), a neurodegenerative disorder in which alpha synuclein accumulates in glial cytoplasmic inclusions
rather than in Lewy bodies. Whereas the three LB disorders involve loss of postganglionic noradrenergic
neurons in the heart, these neurons are usually spared in MSA. Therefore, peripheral noradrenergic
involvement detected by neurochemica! or neuroimaging studies, might be useful as a biomarker of PAF vs.
early "premotor" MSA. In Specific aim 2 we will test the hypothesis that patients who have the clinical
phenotype of PAF but have preserved postganglionic sympathetic neurons do not have PAF but have early
MSA or other as vet undefined disorders.
Effective start/end date7/1/096/30/19


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


Multiple System Atrophy
Autonomic Nervous System Diseases
Rare Diseases
Myelin Basic Protein
Transgenic Mice
Orthostatic Hypotension
Neurogenic Urinary Bladder
Cerebellar Ataxia
Inclusion Bodies
Controlled Clinical Trials
Parkinsonian Disorders
Erectile Dysfunction
Mesenchymal Stromal Cells


  • Medicine(all)
  • Neuroscience(all)