mHTT protein: The fundamental cause of Huntington’s disease 

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); a gain-of-function mutation leading to the production of toxic mutant huntingtin (mHTT) protein.6 The degree of symptom severity, disease stage, and markers of neuronal damage have been shown to correlate with levels of the mHTT protein in the cerebrospinal fluid in individuals with HD. This toxic mHTT causes progressive neuronal degeneration, ultimately leading to neuronal cell death.4-6,33

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 HD was so significant, and how that finding informs today’s research into potential disease-modifying therapies that may slow or stop disease progression. 

The role of the mHTT protein in HD progression

The production of this toxic mutant huntingtin protein leads to progressive neuronal degeneration, ultimately leading to neuronal cell death.34 Levels of mHTT protein in cerebrospinal fluid have been shown to correlate with disease stage, symptom severity and markers of neuronal damage in people with HD.34

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.35

HD protein_mRNA_4.10

Today, we’re building on 100+ years of progress

HD research has come a very long way since the condition was first described in 1872.6,7 Years of research led to the discovery of the mHTT protein as the fundamental cause of HD, opening the door to new avenues of research for future treatment approaches.5

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.

Jump to the New frontiers in the treatment of Huntington's disease section for more information

George Huntington

In 1872, the first clinical description of HD was written by George Huntington.1

Country of Venezuela

After a monumental survey of the largest extended family with HD in Venezuela, the Huntington’s Disease Collaborative Research Group mapped the huntingtin gene (HTT) in 1983.36

mHTT protein

The 1993 discovery of a CAG repeat expansion in the HTT gene revealed the formation of the toxic mHTT protein–the fundamental cause of HD.4,5

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.4,5


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