Huntington's disease affects the brain, causing speech impairment.
Huntington's disease (HD) is "an inherited neurological disease causing involuntary movements, severe emotional disturbance and cognitive decline," according to the National Human Genome Research Institute.
HD is one of many neurological disorders affecting speech, causing a stutter, mispronunciation of words and difficulty making coherent sentences. It is also fatal.
Some 30,000 people in the US have HD, another 35,000 people show some symptoms and 75,000 people carry the abnormal gene that will eventually lead to the disease. For those with the gene, it is unavoidable, and there is no cure.
Understanding of the molecular and neurological dysfunctions that cause the symptoms of HD is limited. A single abnormal gene on chromosome 4 is known to be responsible. The gene codes for production of a protein called "huntingtin," whose function is still unknown.
The defect causes malformation of the protein, which then clumps in the brain, causing the progressive breakdown and death of nearby cells. Cells of the basal ganglia are particularly affected - an area responsible for coordinating movement - and of the cortex, which controls thought, perception and memory.
The defective version of the gene has excessive repeats of a three-base sequence, "CAG." In the normal Huntington gene, this sequence is repeated between 11 and 29 times. In the mutant gene, the repeat occurs over and over again, from 40 times to more than 80.
A 50% chance of HD if one parent has gene
The child of a parent with HD has a 50% chance of inheriting the gene; those who do will ultimately show signs of the disease, usually in mid-life.Those who do not inherit the gene will not develop the disease or pass the gene on to subsequent generations.
- HD affects 1 in 7,300 people in North America and Europe
- It is most common in people of European ancestry
- In British Columbia, there are 17.2 cases per 100,000 among people of European ancestry, but only 2.1 in other ethnic groups.
Researchers at Fernando Nottebohn's Laboratory of Animal Behavior at Rockefeller University in New York have recently used finches to carry out research into neurodegeneration, with interesting results.
As study author Wan-Chun Liu points out, rats and mice - the most common lab animals - cannot reveal much about speech disorders. But songbirds can learn vocalizations.
The songbirds used by Liu are zebra finches - small, red-beaked birds common in pet stores.
Scientists at Rockefeller had previously examined the interplay between the inborn program for song in young birds and the influence of social factors, uncovering parallels to speech acquisition in human babies.
From there came the idea of using songbirds to study the neurological basis for HD.
At the same time, Nottebohm was studying the neural circuits responsible for song learning, including the cortical-basal ganglia pathways.
Genetic change impairs birdsong
Liu bred finches with a singular genetic mutation, the introduction of mHTT, the mutant human gene responsible for HD.
Since HD is determined by a single gene, it was easy to isolate its effects on the birds.
Liu's team introduced the mHTT gene into eggs, then screened the chicks for the mutation after hatching. The affected birds were used to breed successive generations, in whom the genetic mutation occurred naturally. That way, the researchers could ensure that each bird developed the disease as it would manifest in humans.
As they grew, the transgenic finches all displayed behavior disorders associated with Huntington's, such as tremors. Most of the mutant males - the singing sex - had problems learning their songs while young, and, once fully grown, produced aberrant songs.
"Some of the birds stuttered. If the normal song was 'ABCDE,' these mutant birds could only sing 'AAAA.'"
Liu selected the birds that appeared the most vocally impaired, and, using specialized computer software, monitored subtle changes in these finches' songs as their muscular degradation progressed, providing detailed records of how vocal patterns were affected.
This kind of progressive speech impairment is associated with dysfunction in the cortical-basal ganglia brain circuit in both humans and songbirds, so Liu could make assumptions based on this trial about how the human brain circuit changes.
The results are the clearest findings to date as to how this kind of neurodegeneration occurs.
There are significant implications for future drug development, as scientists will now be able to test therapeutic treatments on vocal degeneration. A new drug could be injected into a specific brain area and evaluated by how it impacts the degradation of vocal ability in songbirds.
Liu hopes this could be a turning point, not just for HD, but also for other diseases such as Alzheimer's and Parkinson's.
Medical News Today recently reported that speech patterns in young people could predict future psychosis.
Written by Yvette Brazier