Noradrenergic Drug Treatment of Obstructive Sleep Apnea

Technology #18111

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Noradrenergic A7 and A5 neuronal groups are activated by episodic airway occlusions, as indicated by enhanced cFos expression. This figure shows neurons that were immunopositive to both DBH and c-Fos.Yohimbine data. (A) Shows yohimbine administered by microinjections at bilateral A7 and A5 (n=5) or systematically by intervenous injectin (n=5) increased the amplitude of hypoglossal nerve discharge and enhanced the  airway occlusion-induced hypoglossal long-term facilitation compared with control (n=12). *P<0.05 (vs. preinjection baseline, broken line); #P<0.05. (B) is a replot of (A) for direct comparison of the amplitude of hypoglossal nerve discharge before and after episodic airway occlusion in the hyhimbine microinjection group (left panel) and systemic yohimibine group (right panel). $P<0.05.
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Inventors
Chi-Sang Poon
Institute for Medical Engineering and Science, MIT
Gang Song
Institute for Medical Engineering and Science, MIT
Managed By
Tod Woolf
MIT Technology Licensing Officer
Patent Protection

Noradrenergic Drug Treatment of Obstructive Sleep Apnea

PCT Patent Application Filed

Applications

This invention is an effective pharmacotherapy treatment of sleep apnea. It may also be used for the treatment of any disorder in which the patient benefits from noradrenergic drug treatment including cataplexy, ADHD, ADD, and depression.

Problem Addressed

Current treatments for the common disease obstructive sleep apnea (OSA) include mechanical, surgical, behavioral or electrical interventions but have limited efficacy. Therefore, for improved patient comfort, convenience, and treatment, an efficacious pharmacotherapy is highly desired. It has been discovered that disinhibition of central noradrenergic neurons by α2-adrenoceptor antagonism restores hypoglossal motoneuron excitability and experience-dependent hypoglossal motor learning and memory capacity for increased control of pharyngeal muscle activity thereby mitigating OSA. This technology focuses on α2-adrenoceptors expressed in central noradrenergic neurons as an effective druggable target for the treatment of OSA. 

Technology

It has been shown that A7 and A5 noradrenergic neurons when stimulated (disinhibited) by an α2-adrenoceptor specific antagonist, such as yohimbine, results in up-regulation of hypoglossal motoneuron excitability hence providing an effective treatment for OSA. Furthermore, systematic yohimbine doses enhance experience-dependent learning and memory of the hypoglossal motor defense against airway obstruction during REM sleep. While some adrenoceptor agonists may elicit severe adverse effects, yohimbine has only minor side-effects even with continuous use, making it ideal for the safe treatment of OSA. Because yohimbine is quickly eliminated through metabolism, this treatment requires a new sustained release formulation that may allow novel composition of matter claims. This invention is the first effective pharmacotherapy treatment for OSA.

Advantages

  • Oral drug treatment is less intrusive/invasive and expensive than current OSA treatments such as continuous positive airway pressure, surgery or electrical nerve stimulation
  • Yohminbine is a safe drug that has been routinely used as an herbal supplement with relatively minor side-effects