International Journal of Cell Biology and Cellular Functions Original Research
The Current State of Huntington's Disease Treatment: An Overview of Palliative Care and Symptom Management
Abstract
Huntington's disease (HD) is a neurodegenerative ailment that adversely affects the basal ganglia and the cortex of the brain. Although there is no recognized cure for HD, symptomatic relief and therapeutic management of the condition have improved over the course of time. This review paper provides an up-to-date overview of the current treatment options and symptom management strategies utilized in the care of HD patients. Additionally, it highlights the existing research strategies being employed to develop new treatments or technologies for managing the disease. Finally, the paper examines potential future prospects, including gene therapies and other novel approaches to treating HD. The article concludes that while there is still much work to be done to find a cure for HD, current treatment options and research strategies offer hope for a better quality of life for HD patients and their families.Keywords
References (60)
- Huntington's Disease Society of America. (2016). History of Huntington’s Disease | Huntington’s Disease Society of America. Hdsa.org. https://hdsa.org/what-is-hd/history-and-genetics-of-huntingtons-disease/history-of-huntingtons-disease/
- Stoker TB, Mason SL, Greenland JC, Holden ST, Santini H, Barker RA. Huntington’s disease: diagnosis and management. Practical Neurology. 2021;22(1):32-41. doi:10.1136/practneurol-2021-003074
- Dayalu P, Albin RL. Huntington Disease. Neurologic Clinics. 2015;33(1):101-114. doi:10.1016/j.ncl.2014.09.003
- Caron, N. S., Wright, G. E. B., & Hayden, M. R. (1998). Huntington Disease. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.
- Frank S. Treatment of Huntington's Disease. Neurotherapeutics. 2014;11(1):153-160. doi:10.1007/s13311-013-0244-z
- National Institute of Neurological Disorders and Stroke. (2022, July 25). Huntington’s Disease | National Institute of Neurological Disorders and Stroke. Www.ninds.nih.gov. https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease
- Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, et al. Huntington disease. Nature Reviews Disease Primers. 2015;1(1). doi:10.1038/nrdp.2015.5
- Durr A, Gargiulo M, Feingold J. The presymptomatic phase of Huntington disease. Revue Neurologique. 2012;168(11):806-808. doi:10.1016/j.neurol.2012.07.003
- Mayo Clinic. (2020, April 14). Huntington’s disease - Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117
- Dayalu P, Albin RL. Huntington Disease. Neurologic Clinics. 2015;33(1):101-114. doi:10.1016/j.ncl.2014.09.003
- Walker FO. Huntington's disease. The Lancet. 2007;369(9557):218-228. doi:10.1016/s0140-6736(07)60111-1
- Montoya, A., Price, B. H., Menear, M., & Lepage, M. (2006). Brain imaging and cognitive dysfunctions in Huntington’s disease. Journal of Psychiatry & Neuroscience : JPN, 31(1), 21–29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325063/
- Dickey AS, La Spada AR. Therapy development in Huntington disease: From current strategies to emerging opportunities. American Journal of Medical Genetics Part A. 2017;176(4):842-861. doi:10.1002/ajmg.a.38494
- Aziz NA, van der Marck MA, Pijl H, Olde Rikkert MGM, Bloem BR, Roos RAC. Weight loss in neurodegenerative disorders. Journal of Neurology. 2008;255(12):1872-1880. doi:10.1007/s00415-009-0062-8
- van Duijn E, Kingma EM, van der Mast RC. Psychopathology in Verified Huntington’s Disease Gene Carriers. The Journal of Neuropsychiatry and Clinical Neurosciences. 2007;19(4):441-448. doi:10.1176/jnp.2007.19.4.441
- van der Burg JM, Björkqvist M, Brundin P. Beyond the brain: widespread pathology in Huntington's disease. The Lancet Neurology. 2009;8(8):765-774. doi:10.1016/s1474-4422(09)70178-4
- Myers RH. Huntington’s disease genetics. NeuroRX. 2004;1(2):255-262. doi:10.1602/neurorx.1.2.255
- Katsuno M, Banno H, Suzuki K, Takeuchi Y, Kawashima M, Tanaka F, et al. Molecular Genetics and Biomarkers of Polyglutamine Diseases. Current Molecular Medicine. 2008;8(3):221-234. doi:10.2174/156652408784221298
- Squitieri F, Frati L, Ciarmiello A, Lastoria S, Quarrell O. Juvenile Huntington's disease: Does a dosage-effect pathogenic mechanism differ from the classical adult disease? Mechanisms of Ageing and Development. 2006;127(2):208-212. doi:10.1016/j.mad.2005.09.012
- Nance MA, Myers RH. Juvenile onset Huntington's disease—clinical and research perspectives. Mental Retardation and Developmental Disabilities Research Reviews. 2001;7(3):153-157. doi:10.1002/mrdd.1022
- (2020, August 18). Huntington disease: MedlinePlus Genetics. Medlineplus.gov. https://medlineplus.gov/genetics/condition/huntington-disease/#inheritance
- Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, et al. A Protein Interaction Network Links GIT1, an Enhancer of Huntingtin Aggregation, to Huntington's Disease. Molecular Cell. 2004;15(6):853-865. doi:10.1016/j.molcel.2004.09.016
- Glajch, K. E., & Sadri-Vakili, G. (2015). Epigenetic Mechanisms Involved in Huntington's Disease Pathogenesis. Journal of Huntington's disease, 4(1), 1–15. https://doi.org/10.3233/JHD-159001
- Liu Z, Zhou T, Ziegler AC, Dimitrion P, Zuo L. Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications. Oxidative Medicine and Cellular Longevity. 2017;2017(1). doi:10.1155/2017/2525967
- Cattaneo E, Zuccato C, Tartari M. Normal huntingtin function: an alternative approach to Huntington's disease. Nature Reviews Neuroscience. 2005;6(12):919-930. doi:10.1038/nrn1806
- Rubinsztein DC, Carmichael J. Huntington's disease: molecular basis of neurodegeneration. Expert Reviews in Molecular Medicine. 2003;5(20):1-21. doi:10.1017/s1462399403006549
- Matlahov I, van der Wel PC. Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington’s disease. Experimental Biology and Medicine. 2019;244(17):1584-1595. doi:10.1177/1535370219856620
- Nopoulos PC. Huntington disease: a single-gene degenerative disorder of the striatum. Dialogues in Clinical Neuroscience. 2016;18(1):91-98. doi:10.31887/dcns.2016.18.1/pnopoulos
- Reiner A, Dragatsis I, Dietrich P. Genetics and Neuropathology of Huntington's Disease. International Review of Neurobiology. 2011:325-372. doi:10.1016/b978-0-12-381328-2.00014-6
- Sadri-Vakili G, Cha JHJ. Mechanisms of Disease: histone modifications in Huntington's disease. Nature Clinical Practice Neurology. 2006;2(6):330-338. doi:10.1038/ncpneuro0199
- Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature. 2001;413(6857):739-743. doi:10.1038/35099568
- Petruska J, Hartenstine MJ, Goodman MF. Analysis of Strand Slippage in DNA Polymerase Expansions of CAG/CTG Triplet Repeats Associated with Neurodegenerative Disease. Journal of Biological Chemistry. 1998;273(9):5204-5210. doi:10.1074/jbc.273.9.5204
- Mayo Clinic. (2018). Huntington’s disease - Diagnosis and treatment - Mayo Clinic. Mayoclinic.org. https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/diagnosis-treatment/drc-20356122
- Frank S. Treatment of Huntington's Disease. Neurotherapeutics. 2014;11(1):153-160. doi:10.1007/s13311-013-0244-z
- Ferguson MW, Kennedy CJ, Palpagama TH, Waldvogel HJ, Faull RLM, Kwakowsky A. Current and Possible Future Therapeutic Options for Huntington’s Disease. Journal of Central Nervous System Disease. 2022;14. doi:10.1177/11795735221092517
- de Tommaso. Management of Huntington’s disease: role of tetrabenazine. Therapeutics and Clinical Risk Management. 2011:123. doi:10.2147/tcrm.s17152
- Kim A, Lalonde K, Truesdell A, Gomes Welter P, Brocardo PS, Rosenstock TR, et al. New Avenues for the Treatment of Huntington’s Disease. International Journal of Molecular Sciences. 2021;22(16):8363. doi:10.3390/ijms22168363
- Gibson JS, Claassen DO. State-of-the-art pharmacological approaches to reduce chorea in Huntington’s disease. Expert Opinion on Pharmacotherapy. 2021;22(8):1015-1024. doi:10.1080/14656566.2021.1876666
- Vishwas S, Gulati M, Kapoor B, Gupta S, Singh SK, Awasthi A, et al. Expanding the Arsenal Against Huntington's Disease-Herbal Drugs and Their Nanoformulations. Current Neuropharmacology. 2021;19(7):957-989. doi:10.2174/1570159x18666201109090824
- André VM, Cepeda C, Levine MS. Dopamine and Glutamate in Huntington's Disease: A Balancing Act. CNS Neuroscience & Therapeutics. 2010;16(3):163-178. doi:10.1111/j.1755-5949.2010.00134.x
- McLauchlan DJ, Lancaster T, Craufurd D, Linden DEJ, Rosser AE. Different depression: motivational anhedonia governs antidepressant efficacy in Huntington’s disease. Brain Communications. 2022;4(6). doi:10.1093/braincomms/fcac278
- Tan, V. (n.d.). Antidepressants - Huntington’s Disease News. https://huntingtonsdiseasenews.com/antidepressants/
- A'Campo, L. E., Spliethoff-Kamminga, N. G., & Roos, R. A. (2012). The Patient Education Program for Huntington's Disease (PEP-HD). Journal of Huntington's disease, 1(1), 47–56. https://doi.org/10.3233/JHD -2012-120002
- Living with Huntington’s Disease - Huntington’s Disease News. (2018). Huntington’s Disease News. https://huntingtonsdiseasenews.com/living-with-huntingtons-disease/
- Liou, S. (2011, July 2). About Lifestyle and Huntington’s Disease. HOPES Huntington’s Disease Information. https://hopes.stanford.edu/about-lifestyle-and-huntingtons-disease/
- Tabrizi SJ, Estevez-Fraga C, van Roon-Mom WMC, Flower MD, Scahill RI, Wild EJ, et al. Potential disease-modifying therapies for Huntington's disease: lessons learned and future opportunities. The Lancet Neurology. 2022;21(7):645-658. doi:10.1016/s1474-4422(22)00121-1
- Kaemmerer WF, Grondin R. The effects of huntingtin-lowering: what do we know so far? Degenerative Neurological and Neuromuscular Disease. 2019;Volume9:3-17. doi:10.2147/dnnd.s163808
- Marxreiter F, Stemick J, Kohl Z. Huntingtin Lowering Strategies. International Journal of Molecular Sciences. 2020;21(6):2146. doi:10.3390/ijms21062146
- Djajadikerta A, Keshri S, Pavel M, Prestil R, Ryan L, Rubinsztein DC. Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases. Journal of Molecular Biology. 2020;432(8):2799-2821. doi:10.1016/j.jmb.2019.12.035
- Rosser AE, Busse ME, Gray WP, Badin RA, Perrier AL, Wheelock V, et al. Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder. Brain. 2022;145(5):1584-1597. doi:10.1093/brain/awac086
- Huntington’s Disease Research Directions. (2009, November 21). News-Medical.net. https://www.news-medical.net/health/Huntingtons-Disease-Research-Directions.aspx
- Jurcau A, Jurcau MC. Therapeutic Strategies in Huntington’s Disease: From Genetic Defect to Gene Therapy. Biomedicines. 2022;10(8):1895. doi:10.3390/biomedicines10081895
- Rosser AE, Busse ME, Gray WP, Badin RA, Perrier AL, Wheelock V, et al. Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder. Brain. 2022;145(5):1584-1597. doi:10.1093/brain/awac086
- Dash D, Mestre TA. Therapeutic Update on Huntington's Disease: Symptomatic Treatments and Emerging Disease-Modifying Therapies. Neurotherapeutics. 2020;17(4):1645-1659. doi:10.1007/s13311-020-00891-w
- Tetrabenazine: MedlinePlus Drug Information. (n.d.). Medlineplus.gov. https://medlineplus.gov/druginfo/meds/a618009.html
- Seppi K, Mueller J, Bodner T, Brandauer E, Benke T, Weirich-Schwaiger H, et al. Riluzole in Huntington's disease (HD): an open label study with one year follow up. Journal of Neurology. 2001;248(10):866-869. doi:10.1007/s004150170071
- Yeo K, Gupta M, Correll CU. Huntington’s Disease With Psychotic Features. The Primary Care Companion For CNS Disorders. 2021;23(4). doi:10.4088/pcc.20l02745
- Szymuś K, Bystrzyński A, Kwaśniak-Butowska M, Konkel A, Leśnicka A, Nowacka M, et al. Sexual dysfunction in Huntington’s Disease — a systematic review. Neurologia i Neurochirurgia Polska. 2020;54(4):305-311. doi:10.5603/jnns.a2020.0025
- Mayo Clinic. (2018). Huntington’s disease - Diagnosis and treatment - Mayo Clinic. Mayoclinic.org; Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/diagnosis-treatment/drc-20356122
- Andhale R, Shrivastava D. Huntington's Disease: A Clinical Review. Cureus. 2022. doi:10.7759/cureus.28484