The Protein With Big Impact

Huntington’s disease (HD) is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin gene (HTT ), which leads to the production of the mutant huntingtin (mHTT) protein. The degree of symptom severity, disease stage, and markers of neuronal damage have been shown to correlate with levels of mHTT protein in the cerebrospinal fluid in patients with HD. This toxic mHTT protein production is believed to result in neurotoxicity, as normal cellular processes important for cellular survival are disrupted.1,2

 

How is the understanding of the mHTT protein helping further HD research?

Hear from researchers Nancy Wexler and Lauren Byrne on why the identification of the fundamental cause of Huntington’s disease was so significant, and how that finding informs today’s research.

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mHTT Protein's Role in Huntington's Disease Progression

The production of this toxic mutant huntingtin protein leads to the pathological cascade of Huntington's disease. Levels of mHTT protein in cerebrospinal fluid have been shown to correlate with disease phase, symptom severity, and markers of neuronal damage in people with Huntington’s disease.13

The exact mechanism by which mHTT protein causes neuronal death is still being elucidated, however research suggests that it may interfere with a number of cellular processes such as DNA transcription and axonal transport.10

mHTT protein and HD

Download a PDF about how the mHTT protein leads to the Huntington’s disease cascade.

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Right Now, We’re Building on 100+ Years of Progress

Huntington’s disease research has come a long way since the condition was first described in 1872. Eventually this led to the discovery of mHTT as the underlying cause of HD.2

We’re proud to help further the knowledge of the mHTT protein, in hopes of one day improving the lives of those affected by this condition.

George Huntington

In 1872, the first clinical description of HD was written by George Huntington.3

Country of Venezuela

After a monumental survey of the largest extended family in Venezuela, the Huntington’s Disease Collaborative Research Group identified the huntingtin gene (HTT) in 1983.14

mHTT protein

The 1993 discovery of a CAG repeat expansion in the HTT gene revealed the formation of the toxic mHTT protein—the cause of HD.1,2

A Leader in Huntington’s Disease Research

Today’s milestones are built on the contributions of researchers like Nancy Wexler. Hear her compelling story and why she’s optimistic about the future of HD.1,2

    • Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72:971-983.

      Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72:971-983.

    • Ghosh R, Tabrizi SJ. Huntington disease. In: Geschwind DH, Paulson HL, Klein C, eds. Handbook of Clinical Neurology, Vol 147. Elsevier BV; 2018;255-278. https://doi.org/10.1016/B978-0-444-63233-3.00017-8. 

      Ghosh R, Tabrizi SJ. Huntington disease. In: Geschwind DH, Paulson HL, Klein C, eds. Handbook of Clinical Neurology, Vol 147. Elsevier BV; 2018;255-278. https://doi.org/10.1016/B978-0-444-63233-3.00017-8. 

    • Huntington G. On chorea. J Neuropsychiatry Clin Neurosci. 2003;15(1):109-113.

      Huntington G. On chorea. J Neuropsychiatry Clin Neurosci. 2003;15(1):109-113.

    • Moscovich M, Munhoz RP, Becker N, et al. Américo Negrette and Huntington’s disease. Arq Neuropsiquiatr. 2011;69(4):711-713.

      Moscovich M, Munhoz RP, Becker N, et al. Américo Negrette and Huntington’s disease. Arq Neuropsiquiatr. 2011;69(4):711-713.

    • Rodrigues FB, Byrne LM, Wild EJ. Biofluid biomarkers in Huntington’s Disease. Methods Mol Biol. 2018;1780:329-396.

      Rodrigues FB, Byrne LM, Wild EJ. Biofluid biomarkers in Huntington’s Disease. Methods Mol Biol. 2018;1780:329-396.

    • Yohrling G, Raimundo K, Crowell V, Lovecky D, Vetter L, Seeberger L. Prevalence of Huntington’s Disease in the US [abstract taken from HSG 2019]. Neurotherapeutics. https://doi.org/10.1007/s13311-019-00788-3. Published October 8, 2019.

      Yohrling G, Raimundo K, Crowell V, Lovecky D, Vetter L, Seeberger L. Prevalence of Huntington’s Disease in the US [abstract taken from HSG 2019]. Neurotherapeutics. https://doi.org/10.1007/s13311-019-00788-3. Published October 8, 2019.

    • Bates GP, Dorsey R, Gusella JF, et al. Huntington disease. Nat Rev Dis Primers. 2015;1:15005.

      Bates GP, Dorsey R, Gusella JF, et al. Huntington disease. Nat Rev Dis Primers. 2015;1:15005.

    • Anderson KE, van Duijn E, Craufurd D, et al. Clinical management of neuropsychiatric symptoms of Huntington disease: expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders. J Huntingtons Dis. 2018;7(3):355-366.

      Anderson KE, van Duijn E, Craufurd D, et al. Clinical management of neuropsychiatric symptoms of Huntington disease: expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders. J Huntingtons Dis. 2018;7(3):355-366.

    • Roos RAC. Huntington disease: a clinical review. Orphanet J Rare Dis. 2010;5:40. doi:10.1186/1750-1172-5-40.

      Roos RAC. Huntington disease: a clinical review. Orphanet J Rare Dis. 2010;5:40. doi:10.1186/1750-1172-5-40.

    • Frank S. Treatment of Huntington’s disease. Neurotherapeutics. 2014;11(1):153-160.

      Frank S. Treatment of Huntington’s disease. Neurotherapeutics. 2014;11(1):153-160.

    • Nance M, Paulsen JS, Rosenblatt A, Wheelock V. A Physician’s Guide to the Management of Huntington’s Disease. 3rd ed. New York, NY: Huntington's Disease Society of America; 2011.

      Nance M, Paulsen JS, Rosenblatt A, Wheelock V. A Physician’s Guide to the Management of Huntington’s Disease. 3rd ed. New York, NY: Huntington's Disease Society of America; 2011.

    • Huntington’s Disease Society of America. HDSA Family Guide Series: Physical and Occupational Therapy—Huntington’s Disease. http://hdsa.org/wp-content/uploads/2015/03/PhysicalOccupationalTherapy_FamilyGuide.pdf. Accessed May 17, 2019.

      Huntington’s Disease Society of America. HDSA Family Guide Series: Physical and Occupational Therapy—Huntington’s Disease. http://hdsa.org/wp-content/uploads/2015/03/PhysicalOccupationalTherapy_FamilyGuide.pdf. Accessed May 17, 2019.

    • Wild EJ, Boggio R, Langbehn D, et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients. J Clin Invest. 2015;125(5):1979-1986.

      Wild EJ, Boggio R, Langbehn D, et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients. J Clin Invest. 2015;125(5):1979-1986.

    • Gusella JF, Wexler NS, Conneally PM, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983;306:234-238.

      Gusella JF, Wexler NS, Conneally PM, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature. 1983;306:234-238.