Current treatments in familial dysautonomia

Expert Opin Pharmacother. 2014 Dec;15(18):2653-71. doi: 10.1517/14656566.2014.970530. Epub 2014 Oct 17.


Introduction: Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (type III). The disease is caused by a point mutation in the IKBKAP gene that affects the splicing of the elongator-1 protein (ELP-1) (also known as IKAP). Patients have dramatic blood pressure instability due to baroreflex failure, chronic kidney disease, and impaired swallowing leading to recurrent aspiration pneumonia, which results in chronic lung disease. Diminished pain and temperature perception result in neuropathic joints and thermal injuries. Impaired proprioception leads to gait ataxia. Optic neuropathy and corneal opacities lead to progressive visual loss.

Areas covered: This article reviews current therapeutic strategies for the symptomatic treatment of FD, as well as the potential of new gene-modifying agents.

Expert opinion: Therapeutic focus on FD is centered on reducing the catecholamine surges caused by baroreflex failure. Managing neurogenic dysphagia with effective protection of the airway passages and prompt treatment of aspiration pneumonias is necessary to prevent respiratory failure. Sedative medications should be used cautiously due to the risk of respiratory depression. Non-invasive ventilation during sleep effectively manages apneas and prevents hypercapnia. Clinical trials of compounds that increase levels of IKAP (ELP-1) are underway and will determine whether they can reverse or slow disease progression.

Keywords: future directions; hereditary autonomic neuropathy; hypertensive surges; nausea; splicing modification therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists / pharmacology
  • Adrenergic alpha-1 Receptor Agonists / therapeutic use
  • Blood Pressure / drug effects
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Dopamine Agents / therapeutic use
  • Dysautonomia, Familial / complications
  • Dysautonomia, Familial / drug therapy*
  • Dysautonomia, Familial / genetics
  • Eye Diseases / complications
  • Eye Diseases / drug therapy
  • Gastrointestinal Diseases / complications
  • Gastrointestinal Diseases / drug therapy
  • Humans
  • Lung Diseases / complications
  • Lung Diseases / drug therapy
  • Transcriptional Elongation Factors
  • Urologic Diseases / complications
  • Urologic Diseases / drug therapy


  • Adrenergic alpha-1 Receptor Agonists
  • Carrier Proteins
  • Dopamine Agents
  • Elp1 protein, human
  • Transcriptional Elongation Factors