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Animal Models Provide Hints For How To Fight Huntington's Disease


Stephen Luntz

Stephen has a science degree with a major in physics, an arts degree with majors in English Literature and History and Philosophy of Science and a Graduate Diploma in Science Communication.

Freelance Writer

323 Animal Models Provide Hints For How To Fight Huntington's Disease
Laboratory mice are one of the species helping us understand Huntington's disease. Mirko Sobotta/Shutterstock

Although only five to 10 people in 100,000 worldwide suffer from Huntington's disease, research into its progression helps us understand more common, but more complex, neurodegenerative diseases such as Parkinson's disease.

Huntington's was once considered the prime example of a disease that was entirely genetic, with no environmental influence. Now, however, there is strong evidence that exercise can reduce and delay the symptoms of Huntington's in both mice and humans.


Hopes for treating Huntington's rest on tackling the mutant version of the huntingtin's (HTT) gene, which triggers brain cell deaths. Unfortunately, as Professor Xiao-Jiang Li of Emory University writes in the Proceedings of the National Academy of Science (PNAS), “HTT is essential for early embryonic development.”

However, it is not known if HTT is required in adults. Thus, Li engineered mice to have their HTT genes deleted, but only on exposure to the estrogen-blocker tamoxifen. In doing so, he controlled deletion timing. Triggering the deletion in juvenile mice proved disastrous, as the mice developed a terminal form of pancreatitis. But mice that had aged more than four months survived the deletion apparently unharmed.

"When it comes to gene suppression or editing strategies for Huntington's disease, a major concern has been possible side effects because of huntingtin's essential function," said Li in a statement. "Our studies suggest that such concerns may be allayed if deletion of huntingtin occurs only in the adult brain."

Li acknowledged far more research is needed before we can think about transferring the technique to humans in case more subtle problems manifest in mice.


The same edition of PNAS contains a report on work on zebra finches that helps explain how the HTT gene causes damage.

Studying zebra finches can tell us things about the progression of Huntington's disease that mice can't, because the early symptoms are easier to detect. Wang LiQiang/Shutterstock

Although mice already provide a model for Huntington's disease, the discovery of a similar condition in zebra finches last year was hailed as significant. Being songbirds, finches devote much of their brains, known as "area X," to singing. The loss of capacity to vocalize is an early sign of Huntington's disease. As healthy zebra finches sing the same song all their adult lives, even subtle changes in their song can be a detectable warning sign.

Therefore, senior author Professor Richard Mooney of Duke University caused the Huntington's gene to be expressed only in area X. He found that even though only one kind of brain cell (the medium spiny neuron) was affected, a different type (pallidial neurons) lost their timing.


"That suggests that there's something lost in the complexity of the signals that these output neurons normally transmit," said Mooney in a statement. He hopes pallidial neurons might represent a treatment target.

The team also observed that some birds seem to be able to partially recover their singing capacity, and Mooney hopes this could inspire possible treatments: "If new neurons drive recovery, it may be that the songbird will provide a model for understanding how neural replacement in humans can be used to drive behavioral recovery in a range of neurodegenerative diseases."


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