1 / 27

Relationship Between Parkinson’s Disease and Narcolepsy

Relationship Between Parkinson’s Disease and Narcolepsy. Eunjung Lee Jacinthe Chong Wenjia Dai Zipeng Shang. PHM142 Fall 2014 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson. Outline. What is Parkinson’s Disease and Narcolepsy? Symptoms and Relationship

octavia-marius
Télécharger la présentation

Relationship Between Parkinson’s Disease and Narcolepsy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Relationship Between Parkinson’s Disease and Narcolepsy Eunjung Lee Jacinthe Chong Wenjia Dai Zipeng Shang PHM142 Fall 2014 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson

  2. Outline • What is Parkinson’s Disease and Narcolepsy? • Symptoms and Relationship • Mechanisms of Dopamine and Hypocretin • PD Extrapyramidal System • Hypocretin synthesis and action • Demographics and Relationship • Treatment • Narcolepsy and PD drugs

  3. What is Narcolepsy? • Chronic neurological disease characterized by: • Excessive Daytime Sleepiness (EDS) • Cataplexy (muscle weakness) • Abnormal REM sleep • Linked to the peptide hypocretin (orexin) deficiency in the cerebrospinal fluid

  4. What is Parkinson’s Disease? • Progressive neurodegenerative disease • Most commonly known for motor symptoms • Bradykinesia, rigidity, resting tremor • Also accompanied with non-motor symptoms • Sleep disorders • Mood disorders and cognitive deficits • Can have sleep attacks that resemble narcoleptic sleep attacks

  5. How are they linked? • Share symptoms of sleep disorders • Degeneration of cells that produce hypocretin in PD • Lower hypocretin levels in narcolepsy • Many patients with advanced PD also display most symptoms of narcolepsy

  6. Mechanism of Dopamine and Hypocretin

  7. Parkinson’s Disease: Extrapyramidal System

  8. Synthesis of Dopamine and Norepinephrine

  9. Narcolepsy

  10. Hypothalamus and Hypocretin

  11. Autoimmunity • Suspected autoimmune response killing hypocretin-secreting neurons • Polymorphisms in HLA gene encoding for HLA proteins and MHC proteins • Antigens presented on cell surface of neurons • For narcolepsy, variant in TCRA gene as well, encoding for receptor on T-cells • Increased likelihood of T-cells producing autoimmune response • Dopaminergic neurons in substantianigra also present MHC-1 proteins, targeted by T-cells in Parkinson’s Disease

  12. Demographics and Relationship between Narcolepsy and Parkinson’s Disease

  13. Normal level of dopamine ↓ level of dopamine Age of onset mostly between 50-60 Age of onset usually between 35-45 ↓ level of hypocretin 1 million patients in US 20 million patients worldwide 150,000 patients in America 3 million patients worldwide • - Daytime sleep attacks • Nocturnal insomnia • REM sleep disorder • Hallucinations • Depression Slightly higher rate of incidence in men ↑ rate of occurrence inwhites ↓ African-Americans and Asians ↑ in Japanese people (1/600) And ↓ Israel and US

  14. Does one cause the other? • Daytime sleepiness in 76% of PD patients • 75% of patients with REM sleep behavior disorder developed Parkinsonian conditions • However no direct evidence for narcolepsy causing Parkinson’s Disease

  15. Drug Therapy for Narcolepsy and Parkinson’s Disease

  16. Narcolepsy: Symptoms & Treatments Cataplexy • Sodium oxybate • Antidressants Excessive Daytime Sleepiness and Sleep Attacks • Amphetamines • Methylphenidate • Modafinil • Sodium oxybate

  17. Narcolepsy: Symptoms & Treatments Excessive Daytime Sleepiness and Sleep Attacks • Amphetamines • Methylphenidate • Modafinil • Sodium oxybate • Central nervous system stimulants • Early treatment for EDS and sleep attacks • Patients can develop tolerance • Not commonly prescribed since modafinil came onto the market

  18. Narcolepsy: Symptoms & Treatments Excessive Daytime Sleepiness and Sleep Attacks • Amphetamines • Methylphenidate • Modafinil • Sodium oxybate • Central nervous system stimulants • Most commonly prescribed for EDS in narcolepsy • Side effects: headache and nausea

  19. Narcolepsy: Symptoms & Treatments Cataplexy • Sodium oxybate • Antidressants Excessive Daytime Sleepiness and Sleep Attacks • CNS depressant • Can treat both EDS and cataplexy • Contraindicated for sedative hypnotic agents and alcohol

  20. Treatment of Motor Symptoms of Parkinson’s Disease • Levodopa • Converted into dopamine in presynaptic dopaminergic neurons • Effects enhanced with DOPA decarboxylase inhibitors such as carbidopa • Most effective therapy, but associated with motor complications • Dopamine agonists • Modest efficacy in early stages of PD • E.g. pramipexole, ropininirole, pergolide (removed from market) • Anticholinergics • Not recommended due to side effects

  21. Side effects of PD drugs • Sleep attacks associated with dopaminergic drugs. • Stimulating D3 receptors increases incidence of sleep attacks • Due to reduction of hypocretin levels in the CSF. • Replacing pramipexole with pergolide resolved sleep attacks and increased hypocretin levels in the CSF.

  22. Narcolepsy Drugs for the Treatment of Sleep Disorders in PD? • Modafinil • 3 studies, conflicting results • Insufficient evidence for efficacy in treatment of EDS in PD patients. • Sodium oxybate • One study showed promising results. • Insufficient evidence

  23. Possible Future Therapies? • Hypocretin • BBB is impermeable • Hypocretin agonists • None reported yet • Hypocretin systems have been used to treat sleep disorders • Hypocretin receptor antagonist for treatment of insomnia

  24. References • Asai, H., Hirano, M., Furiya, Y., Udaka, F., Morikawa, M., Kanbayashi, T., Shimizu, T., and Ueno, S. (2009). ClinNeurolNeurosurg, 111(4), 341-344. doi: 10.1016/j.clineuro.2008.11.007. • Billiard, M. (2008). Narcolepsy: current treatment options and future approaches. Neuropsychiatr Dis Treat, 4(3), 557-566. • Cebrián C, Zucca FA, Mauri P, Steinbeck JA, Studer L, Scherzer CR, Kanter E, Budhu S, Mandelbaum J, Vonsattel JP, Zecca L, Loike JD, Sulzer D (2014) MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration. Nat Comms 5:3633. DOI: 10.1038/ncomms4633 http://dx.doi.org/10.1038/ncomms4633 • e-CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2014 [cited 2014 Oct 9]. Available from: http://www.e-cps.ca. Also available in paper copy from the publisher. • Gray Jean, editor. e-Therapeutics+ [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2014 [cited 2014 Oct 9]. Available from: http://www.e-therapeutics.ca.myaccess.library.utoronto.ca Also available in paper copy from the publisher. • Haq, I.Z.; Naidu, Y.; Reddy, P. & Chaudhuri, K.R. (2010). Narcolepsy in Parkinson’s disease. Expert Review of Neurotherapeutics, 10(6), 879-884. doi: 10.1586/ern.10.56 • Hungs, M. & Mignot, E. (2001). Hypocretin/orexin, sleep and narcolepsy. BioEssays : news and reviews in molecular, cellular and developmental biology, 23(5), 379-408. doi: 10.1002/bies.1058 • Jankovic, J., & Aguilar L.G. (2008). Current approaches to the treatment of Parkinson’s disease. Neuropsychiatr Dis Treat, 4(4): 743-757. • Kobayashi, K. (2001). Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. Journal of Investigative Dermatology Symposium Proceedings, 6(1), 115-121. doi: 10.1046/j.0022-202x.2001.00011.x

  25. Kornum, B. R., Faraco, J., & Mignot, E. (2011). Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain. Current Opinion in Neurobiology, 21(6), 897-903. • Mieda, M., and Sakurai, T. (2013). Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. CNS Drugs, 27(2), 83-90. doi: 10.1007/s40263-012-0036-8. • National Sleep Foundation. (2014). Parkinson's Disease and Sleep. Retrieved October 18, 2014 from http://sleepfoundation.org/sleep-topics/parkinsons-disease-and-sleep • Nishino, S. (2007). Clinical And Neurobiological Aspects Of Narcolepsy.Sleep Medicine, 8(4), 373-399. • Ondo, W.G., Perkins, T., Swick, T., Hull, K.L., Jimenez, J.E., Garris, T.S., and Pardi, D. (2008). Sodium oxybate for excessive daytime sleepiness in parkinson disease. Arch Neurol, 65(10), 1337-1340. doi: 10.1001/archneur.65.10.1337. • Seppi, K., Weintraub, D., Coelho, M., Perez-Lloret, S., Fox, S. H., Katzenschlager, R., Hametner, E.-M., Poewe, W., Rascol, O., Goetz, C. G. and Sampaio, C. (2011). The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease. MovDisord, 26: S42–S80. doi: 10.1002/mds.23884 • Swick, T. J. (2012). Parkinson's Disease and Sleep/Wake Disturbances. Parkinson's Disease, 2012, 1-14. • UCLA. (2007, May 4). Link Between Parkinson's And Narcolepsy Discovered. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2007/05/070504122134.htm

  26. Summary Overview: • Parkinson’s Disease: progressive neurodegenerative disease well known for motor symptoms but also include non-motor symptoms like sleep disorders • Narcolepsy: chronic neurological disease characterized by excessive daytime sleepiness, cataplexy, and abnormal REM sleep behavior Relationship: • Both diseases have a decrease in hypocretin levels (or neurons secreting hypocretin) – believed to be responsible for sleep symptoms in both diseases • Polymorphisms in HLA gene lead to antigen presenting neurons in the brain, becoming a target for T-cells to attack and destroy neurons that regulate the sleep-wake cycle • No evidence to show one causing the other but share common sleep disorder symptoms that can potentially be treated with same classes of drugs Function of Hypocretin: • To integrate information from different systems in the body (i.e. the circadian cycle) in order to determine or promote wakefulness • Stimulates catecholaminergic(dopamine, norepinephrine and epinephrine) pathways in the brain stabilizing wakefulness or sleep Drugs: • Modafinil and Sodium oxybate are used to treat narcolepsy while Levodopa and dopamine agonists are used to treat PD • Hypocretin agonists are a possible future therapy for narcolepsy and sleep disorder symptoms in PD

More Related