The Current State of Huntington’s Disease Treatment: An Overview of Palliative Care and Symptom Management

[{“box”:0,”content”:”[user_role]

n

n

n

n

n

By

n

n

    n t

  1. n

      [foreach 286]n

      1. n

    n

    n

    Richa Sanyal

    n

    n

      n t

    1. n

    [/foreach]n

    n

    n

      [foreach 286] [if 1175 not_equal=””]n t

    1. Student,Department of Biotechnology, University Institute of Biotechnology, Chandigarh University,Punjab,India

      2. n[/if 1175][/foreach]

    n

    n

    n

    n

    n

    Abstract

    nHuntington’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.

    n

    n

    n

    Keywords: Huntington’s disease, chorea, CAG trinucleotides, tetrabenazine, ASO therapies, RNA interference therapy, stem cell therapy, zinc-finger therapies

    n[if 424 equals=”Regular Issue”][This article belongs to International Journal of Cell Biology and Cellular Functions(ijcbcf)]

    n

    [/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in International Journal of Cell Biology and Cellular Functions(ijcbcf)][/if 424][if 424 equals=”Conference”]This article belongs to Conference [/if 424]

    n

    n

    nn

    nn

    Full Text

    nn[if 992 equals=”Open Access”]https://storage.googleapis.com/journals-stmjournals-com-wp-media-to-gcp-offload/2023/06/9ce00bf0-35-52-the-current-state-of-huntington-disease.pdfn[else]nnvar fieldValue = “[user_role]”;nif (fieldValue == ‘indexingbodies’) {ndocument.write(‘‘);ndocument.write(‘https://storage.googleapis.com/journals-stmjournals-com-wp-media-to-gcp-offload/2023/06/9ce00bf0-35-52-the-current-state-of-huntington-disease.pdf’);n} else if (fieldValue === ‘administrator’) {ndocument.write(‘‘);ndocument.write(”);n}else if (fieldValue === ‘ijcbcf’) {n document.write(‘‘);n} else {n document.write(‘ ‘);n}nn[/if 992]n

    n[if 379 not_equal=””]n

    Browse Figures

    n

    n

    [foreach 379]n

    n[/foreach]n

    nn

    n

    n[/if 379]n

    n

    References

    n[if 1104 equals=””]n

    1. 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/
    2. Stoker, T. B., Mason, S. L., Greenland, J. C., Holden, S. T., Santini, H., & Barker, R. A. (2022). Huntington’s disease: diagnosis and management. Practical neurology, 22(1), 32–41. https://doi.org/10.1136/practneurol-2021-003074
    3. Dayalu, P., & Albin, R. L. (2015). Huntington disease: pathogenesis and treatment. Neurologic clinics, 33(1), 101–114. https://doi.org/10.1016/j.ncl.2014.09.003
    4. 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.
    5. Frank S. (2014). Treatment of Huntington’s disease. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics, 11(1), 153–160. https://doi.org/10.1007/s13311-013-0244-z
    6. 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
    7. Bates, G. P., Dorsey, R., Gusella, J. F., Hayden, M. R., Kay, C., Leavitt, B. R., Nance, M., Ross, C. A., Scahill, R. I., Wetzel, R., Wild, E. J., & Tabrizi, S. J. (2015). Huntington disease. Nature reviews. Disease primers, 1, 15005. https://doi.org/10.1038/nrdp.2015.5
    8. Durr, A., Gargiulo, M., & Feingold, J. (2012). The presymptomatic phase of Huntington disease. Revue neurologique, 168(11), 806–808. https://doi.org/10.1016/j.neurol.2012.07.003
    9. 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
    10. Dayalu, P., & Albin, R. L. (2015). Huntington Disease. Neurologic Clinics, 33(1), 101–114. https://doi.org/10.1016/j.ncl.2014.09.003
    11. Walker F. O. (2007). Huntington’s disease. Lancet (London, England), 369(9557), 218–228. https://doi.org/10.1016/S0140-6736(07)60111-1
    12. 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/
    13. Dickey, A. S., & La Spada, A. R. (2018). Therapy development in Huntington disease: From current strategies to emerging opportunities. American journal of medical genetics. Part A, 176(4), 842–861. https://doi.org/10.1002/ajmg.a.38494
    14. Aziz, N. A., van der Marck, M. A., Pijl, H., Olde Rikkert, M. G., Bloem, B. R., & Roos, R. A. (2008). Weight loss in neurodegenerative disorders. Journal of neurology, 255(12), 1872–1880. https://doi.org/10.1007/s00415-009-0062-8
    15. van Duijn, E., Kingma, E. M., & van der Mast, R. C. (2007). Psychopathology in verified Huntington’s disease gene carriers. The Journal of neuropsychiatry and clinical neurosciences, 19(4), 441–448. https://doi.org/10.1176/jnp.2007.19.4.441
    16. van der Burg, J. M., Björkqvist, M., & Brundin, P. (2009). Beyond the brain: widespread pathology in Huntington’s disease. The Lancet. Neurology, 8(8), 765–774. https://doi.org/10.1016/S1474-4422(09)70178-4
    17. Myers R. H. (2004). Huntington’s disease genetics. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics, 1(2), 255–262. https://doi.org/10.1602/neurorx.1.2.255
    18. Katsuno, M., Banno, H., Suzuki, K., Takeuchi, Y., Kawashima, M., Tanaka, F., Adachi, H., & Sobue, G. (2008). Molecular genetics and biomarkers of polyglutamine diseases. Current molecular medicine, 8(3), 221–234. https://doi.org/10.2174/156652408784221298
    19. Squitieri, F., Frati, L., Ciarmiello, A., Lastoria, S., & Quarrell, O. (2006). Juvenile Huntington’s disease: does a dosage-effect pathogenic mechanism differ from the classical adult disease?. Mechanisms of ageing and development, 127(2), 208–212. https://doi.org/10.1016/j.mad.2005.09.012
    20. Nance, M. A., & Myers, R. H. (2001). Juvenile onset Huntington’s disease–clinical and research perspectives. Mental retardation and developmental disabilities research reviews, 7(3), 153–157. https://doi.org/10.1002/mrdd.1022
    21. (2020, August 18). Huntington disease: MedlinePlus Genetics. Medlineplus.gov. https://medlineplus.gov/genetics/condition/huntington-disease/#inheritance
    22. Goehler, H., Lalowski, M., Stelzl, U., Waelter, S., Stroedicke, M., Worm, U., Droege, A., Lindenberg, K. S., Knoblich, M., Haenig, C., Herbst, M., Suopanki, J., Scherzinger, E., Abraham, C., Bauer, B., Hasenbank, R., Fritzsche, A., Ludewig, A. H., Büssow, K., Coleman, S. H., … Wanker, E. E. (2004). A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington’s disease. Molecular cell, 15(6), 853–865. https://doi.org/10.1016/j.molcel.2004.09.016
    23. 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
    24. Liu, Z., Zhou, T., Ziegler, A. C., Dimitrion, P., & Zuo, L. (2017). Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications. Oxidative medicine and cellular longevity, 2017, 2525967. https://doi.org/10.1155/2017/2525967
    25. Cattaneo, E., Zuccato, C., & Tartari, M. (2005). Normal huntingtin function: an alternative approach to Huntington’s disease. Nature reviews. Neuroscience, 6(12), 919–930. https://doi.org/10.1038/nrn1806
    26. Rubinsztein, D. C., & Carmichael, J. (2003). Huntington’s disease: molecular basis of neurodegeneration. Expert reviews in molecular medicine, 5(20), 1–21. https://doi.org/10.1017/S1462399403006549
    27. Matlahov, I., & van der Wel, P. C. (2019). Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington’s disease. Experimental biology and medicine (Maywood, N.J.), 244(17), 1584–1595. https://doi.org/10.1177/1535370219856620
    28. Nopoulos P. C. (2016). Huntington disease: a single-gene degenerative disorder of the striatum. Dialogues in clinical neuroscience, 18(1), 91–98. https://doi.org/10.31887/DCNS.2016.18.1/pnopoulos
    29. Reiner, A., Dragatsis, I., & Dietrich, P. (2011). Genetics and neuropathology of Huntington’s disease. International review of neurobiology, 98, 325–372. https://doi.org/10.1016/B978-0-12-381328-2.00014-6
    30. Sadri-Vakili, G., & Cha, J. H. (2006). Mechanisms of disease: Histone modifications in Huntington’s disease. Nature clinical practice. Neurology, 2(6), 330–338. https://doi.org/10.1038/ncpneuro0199
    31. Steffan, J. S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B. L., Kazantsev, A., Schmidt, E., Zhu, Y. Z., Greenwald, M., Kurokawa, R., Housman, D. E., Jackson, G. R., Marsh, J. L., & Thompson, L. M. (2001). Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature, 413(6857), 739–743. https://doi.org/10.1038/35099568
    32. Petruska, J., Hartenstine, M. J., & Goodman, M. F. (1998). Analysis of strand slippage in DNA polymerase expansions of CAG/CTG triplet repeats associated with neurodegenerative disease. The Journal of biological chemistry, 273(9), 5204–5210. https://doi.org/10.1074/jbc.273.9.5204
    33. 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
    34. Frank S. (2014). Treatment of Huntington’s disease. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics, 11(1), 153–160. https://doi.org/10.1007/s13311-013-0244-z
    35. Ferguson, M. W., Kennedy, C. J., Palpagama, T. H., Waldvogel, H. J., Faull, R. L. M., & Kwakowsky, A. (2022). Current and Possible Future Therapeutic Options for Huntington’s Disease. Journal of central nervous system disease, 14, 11795735221092517. https://doi.org/10.1177/11795735221092517
    36. de Tommaso, M., Serpino, C., & Sciruicchio, V. (2011). Management of Huntington’s disease: role of tetrabenazine. Therapeutics and clinical risk management, 7, 123–129. https://doi.org/10.2147/TCRM.S17152
    37. Kim, A., Lalonde, K., Truesdell, A., Gomes Welter, P., Brocardo, P. S., Rosenstock, T. R., & Gil-Mohapel, J. (2021). New Avenues for the Treatment of Huntington’s Disease. International journal of molecular sciences, 22(16), 8363. https://doi.org/10.3390/ijms22168363
    38. Gibson, J. S., & Claassen, D. O. (2021). State-of-the-art pharmacological approaches to reduce chorea in Huntington’s disease. Expert opinion on pharmacotherapy, 22(8), 1015–1024. https://doi.org/10.1080/14656566.2021.1876666
    39. Vishwas, S., Gulati, M., Kapoor, B., Gupta, S., Singh, S. K., Awasthi, A., Khan, A., Goyal, A., Bansal, A., Baishnab, S., Singh, T. G., Arora, S., Porwal, O., Kumar, A., & Kumar, V. (2021). Expanding the Arsenal Against Huntington’s Disease-Herbal Drugs and Their Nanoformulations. Current neuropharmacology, 19(7), 957–989. https://doi.org/10.2174/1570159X18666201109090824
    40. André, V. M., Cepeda, C., & Levine, M. S. (2010). Dopamine and glutamate in Huntington’s disease: A balancing act. CNS neuroscience & therapeutics, 16(3), 163–178. https://doi.org/10.1111/j.1755-5949.2010.00134.x
    41. McLauchlan, D. J., Lancaster, T., Craufurd, D., Linden, D. E. J., & Rosser, A. E. (2022). Different depression: motivational anhedonia governs antidepressant efficacy in Huntington’s disease. Brain communications, 4(6), fcac278. https://doi.org/10.1093/braincomms/fcac278
    42. Tan, V. (n.d.). Antidepressants – Huntington’s Disease News. https://huntingtonsdiseasenews.com/antidepressants/
    43. 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
    44. Living with Huntington’s Disease – Huntington’s Disease News. (2018). Huntington’s Disease News. https://huntingtonsdiseasenews.com/living-with-huntingtons-disease/
    45. 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/
    46. Tabrizi, S. J., Estevez-Fraga, C., van Roon-Mom, W. M. C., Flower, M. D., Scahill, R. I., Wild, E. J., Muñoz-Sanjuan, I., Sampaio, C., Rosser, A. E., & Leavitt, B. R. (2022). Potential disease-modifying therapies for Huntington’s disease: lessons learned and future opportunities. The Lancet Neurology, 21(7), 645–658. https://doi.org/10.1016/s1474-4422(22)00121-1
    47. Kaemmerer, W. F., & Grondin, R. C. (2019). The effects of huntingtin-lowering: what do we know so far?. Degenerative neurological and neuromuscular disease, 9, 3–17. https://doi.org/10.2147/DNND.S163808
    48. Marxreiter, F., Stemick, J., & Kohl, Z. (2020). Huntingtin Lowering Strategies. International journal of molecular sciences, 21(6), 2146. https://doi.org/10.3390/ijms21062146
    49. Djajadikerta, A., Keshri, S., Pavel, M., Prestil, R., Ryan, L., & Rubinsztein, D. C. (2020). Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases. Journal of molecular biology, 432(8), 2799–2821. https://doi.org/10.1016/j.jmb.2019.12.035
    50. Rosser, A. E., Busse, M. E., Gray, W. P., Badin, R. A., Perrier, A. L., Wheelock, V., Cozzi, E., Martin, U. P., Salado-Manzano, C., Mills, L. J., Drew, C., Goldman, S. A., Canals, J. M., & Thompson, L. M. (2022). Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder. Brain: a journal of neurology, 145(5), 1584–1597. https://doi.org/10.1093/brain/awac086
    51. Huntington’s Disease Research Directions. (2009, November 21). News-Medical.net. https://www.news-medical.net/health/Huntingtons-Disease-Research-Directions.aspx
    52. Jurcau, A., & Jurcau, M. C. (2022). Therapeutic Strategies in Huntington’s Disease: From Genetic Defect to Gene Therapy. Biomedicines, 10(8), 1895. https://doi.org/10.3390/biomedicines10081895
    53. Rosser, A. E., Busse, M. E., Gray, W. P., Badin, R. A., Perrier, A. L., Wheelock, V., Cozzi, E., Martin, U. P., Salado-Manzano, C., Mills, L. J., Drew, C., Goldman, S. A., Canals, J. M., & Thompson, L. M. (2022). Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder. Brain: a journal of neurology, 145(5), 1584–1597. https://doi.org/10.1093/brain/awac086
    54. Dash, D., & Mestre, T. A. (2020). Therapeutic Update on Huntington’s Disease: Symptomatic Treatments and Emerging Disease-Modifying Therapies. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics, 17(4), 1645–1659. https://doi.org/10.1007/s13311-020-00891-w
    55. Tetrabenazine: MedlinePlus Drug Information. (n.d.). Medlineplus.gov. https://medlineplus.gov/druginfo/meds/a618009.html
    56. Seppi, K., Mueller, J., Bodner, T., Brandauer, E., Benke, T., Weirich-Schwaiger, H., Poewe, W., & Wenning, G. K. (2001). Riluzole in Huntington’s disease (HD): an open label study with one year follow up. Journal of Neurology, 248(10), 866–869. https://doi.org/10.1007/s004150170071
    57. Yeo, K., Gupta, M., & Correll, C. U. (2021). Huntington’s Disease With Psychotic Features. The Primary Care Companion for CNS Disorders, 23(4). https://doi.org/10.4088/pcc.20l02745
    58. Szymuś, K., Bystrzyński, A., Kwaśniak-Butowska, M., Konkel, A., Leśnicka, A., Nowacka, M., & Sławek, J. (2020). Sexual dysfunction in Huntington’s Disease – a systematic review. Neurologia i neurochirurgia polska, 54(4), 305–311. https://doi.org/10.5603/JNNS.a2020.0025
    59. 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
    60. Andhale, R., & Shrivastava, D. (2022). Huntington’s Disease: A Clinical Review. Cureus, 14(8), e28484. https://doi.org/10.7759/cureus.28484

    nn[/if 1104][if 1104 not_equal=””]n

      [foreach 1102]n t

    1. [if 1106 equals=””], [/if 1106][if 1106 not_equal=””],[/if 1106]

      2. n[/foreach]

    n[/if 1104]

    nn

    nn[if 1114 equals=”Yes”]n

    n[/if 1114]

    n

    n

    Regular Issue Subscription Original Research

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    n

    Volume 01
    Issue 01
    Received April 13, 2023
    Accepted May 3, 2023
    Published May 17, 2023

    n

    n

    Views: 527
    n

    [if 1190 not_equal=””]n

    Editor

    n

    [foreach 1188]n

    n[/foreach]

    n[/if 1190] [if 1177 not_equal=””]n

    Reviewer

    n

    [foreach 1176]n

    n[/foreach]

    n[/if 1177]

    n

    nn .post-views{n text-align: center;n }n .ALLreveiwers img,.ALLeditors img{n width: 50px;n height: 50px;n border-radius: 50px;n margin: 10px;n }n .ALLreveiwers,.ALLeditors{n border-bottom:1px solid black;n }n .modaltext{color:white; padding: 0px 30px 0px 30px; text-decoration:none;}n .modaltext:hover{color:black background-color:rgb(255 221 204); color:black;}n .modal-content{ margin-top: 50%;}n Edit n function myfun() {n x=document.getElementById(“editor”);n y=document.getElementById(“down”);n z=document.getElementById(“up”);n if(x.style.display==”none”){n x.style.display=”block”;n }n else {n x.style.display=”none”;n }n if(y.style.display==”none”){n y.style.display=”block”;n }n else {n y.style.display=”none”;n }n if(z.style.display==”none”){n z.style.display=”block”;n }n else {n z.style.display=”none”;n }n }n function myfun2() {n x=document.getElementById(“reviewer”);n y=document.getElementById(“down2”);n z=document.getElementById(“up2″);n if(x.style.display==”none”){n x.style.display=”block”;n }n else {n x.style.display=”none”;n }n if(y.style.display==”none”){n y.style.display=”block”;n }n else {n y.style.display=”none”;n }n if(z.style.display==”none”){n z.style.display=”block”;n }n else {n z.style.display=”none”;n }n }n n table, tr, td{n padding: 10px;n border: none;n }n

    n

    n

    n h2{font-size:16px !important; font-family: ‘Roboto’, Slab !important; line-height: 1.4em;}n h3{font-size:18px !important;font-family: ‘Roboto’, Slab !important;}n h4{font-family: ‘Roboto’, Slab !important;}n a{color:blue; font-size:15px !important;font-family: ‘Roboto’, Slab !important;}n li, p{font-size: 15px !important; font-family: ‘Roboto’, Slab !important; text-align: justify;}n .authdiv img{max-width:17px; max-height:17px;}n .authdiv{display:flex; padding: 1px 2px;”}n n function myFunction2() {n var x = document.getElementById(“browsefigure”);n if (x.style.display === “block”) {n x.style.display = “none”;}n else {x.style.display = “Block”;}}n document.querySelector(“.prevBtn”).addEventListener(“click”, () => {n changeSlides(-1);});n document.querySelector(“.nextBtn”).addEventListener(“click”, () => {n changeSlides(1);});n var slideIndex = 1;n showSlides(slideIndex);n function changeSlides(n) {n showSlides((slideIndex += n));}n function currentSlide(n) {n showSlides((slideIndex = n));}n function showSlides(n) {n var i;n var slides = document.getElementsByClassName(“Slide”);n var dots = document.getElementsByClassName(“Navdot”);n if (n > slides.length) {slideIndex = 1;}n if (n (item.style.display = “none”));n Array.from(dots).forEach(n item => (item.className = item.className.replace(” selected”, “”))n );n slides[slideIndex – 1].style.display = “block”;n dots[slideIndex – 1].className += ” selected”;n }n

    “}]