Huntington's disease is a neurodegenerative disorder affecting many (possibly all) parts of the brain. Onset usually occurs between thirty and fifty years of age, and the symptoms become progressively worse over the next ten or fifteen. Death is often due to pneumonia, as the Huntington's victim eventually becomes unable to cough well enough to clear the lungs of infectious matter. The primary symptom, uncontrollable movements known as chorea, comes from the death of neurons in the basal ganglia. Other symptoms include loss of general intellectual function as well as dementia, both caused by neuron death in other brain areas, notably over the entire cerebral cortex.

Mutation of a single gene, named huntingtin, seems to be entirely responsible for the disease. A repeated sequence of CAG codons is part of the huntingtin protein's structure, even when it is working correctly. When a stuttering mutation causes there to be 36 or more repeats, the huntingtin protein will be pathological, and the victim will eventually get Huntington's. With 35 or fewer repeats, no symptoms or problems will ever occur. Because of this easily identified genetic basis, testing can be done to determine positively whether or not a patient will get Huntington's later in life.

Exactly how the mutant huntingtin protein interferes with neurons is still in question, with new research being published monthly. One theory is that the long chain of glutamine (which is coded for by CAG) can become entangled with the glutamine chains of other proteins, such as CPB. These entanglements would aggregate and cause plaques that are dangerous to the neuron, much as with Alzheimer's disease. Another possibility is that the mutant huntingtin protein interferes with brain-derived neurotrophic factor (BDNF). This is supported by the fact that neurons with the BDNF gene knocked out die in much the same way as Huntington's neurons, and that cells cultured with the mutant huntingtin produce little or no BDNF.

The precise mechanism of neuron death in Huntington's is also not known, but some general features are. Neuron death appears to be caused by excitotoxicity, much like the Olney's lesions caused by interference with NMDA channels. Excitotoxicity happens when a neuron is flooded excitatory amino acids (glutamate in particular) released from surrounding neurons. Neuron death follows from excitotoxicity because the neuron is overstimulated for too long a period, which overheats it to the point of death -- the neuron literally burns out. When each neuron dies it releases stored up excitatory amino acids, and the process continues in a chain reaction. This process is probably made much worse by the damage already done to neurons by the huntingtin proteins, as described above.

Both the mechanism and area non-selectivity of this process closely resemble the damage done in Olney's lesions. I would guess that the brain damage done by extreme dissociative drug abuse would closely resemble early stages of Huntington's disease.

Huntington's disease affects approximately 1/10,000 of the general population. The genetic cause is a flaw in chromosome 4. In the normal case there are 4-35 repeats of the CAG sequence.

The number of CAG repeats directly affects the severity of the disease. Individuals with a higher number of extra repeats usually experience earlier onset of symptoms.

Successes in some Animal studies involving fetal tissue transplant into the striatum suggested a possibility that transplant treatments might be effective in humans. Several early attempts included some positive reports, however there had been no proper or rigorous protocols developed or completed. Studies with complete and agreed protocols are now in progress. Research has also been performed in porcine tissue transplants.

Huntington's researchers are also engaging in drug discovery methods, looking at both gene therapy methods and means to either inhibit the malfunction of the damaged huntingtin protein or help the body to fight the problem.


Huntington’s Disease:

This inherited condition is fatal and usually ends with the patient choking or dying of pneumonia. This condition is also known as Huntington's Chorea


The most noticeable symptom of Huntngton's disease is continuous involuntary, out of control, movement across the whole body. Eventually, the abilities to speak, stand, and walk are impaired. Dementia occurs as learning difficulties and thinking problems. There may also be changes in personality, such as depression.

Neurpathological Observations:

Neuropathological observations have shown that sufferers have general brain shrinkage of up to 20%, with a loss of neurons over a wide range of structures, but most significantly in the striatum where 95% of neurons can be lost in advanced cases. MRI imaging techniques have detected large increases in the size of the ventricles of the brain as tissue recedes, while PET scans show that there is a reduction in glucose metabolism in the striatum, which may be the reason these cells die. Levels of dopamine and glutamate seem fairly normal, just a slight elevation and reduction respectively in advanced cases. However, this constant level of dopamine may contribute to the problem. Some of the cells which degenerate are GABA cells which act to inhibit dopamine. The lost of this inhibitory device could be a significant factor in the progression of Huntington’s disease. This view is further supported by the observations that dopamine antagonists tend to alleviate symptoms, whereas L-DOPA has been found to exacerbate them.


There are very few effective treatments for Huntington’s disease, and no means at all to halt its progression. However, the most logical course of action seemed to be finding a way to alleviate the GABA degeneration, in a similar way to the dopamine replacement in Parkinson's disease sufferers. But such a method has failed to work because the GABA system acts too quickly and the simple artificial replenishment of GABA does not mimic normal function. This additional GABA also affects surrounding areas of the striatum which are not degenerating. The only currently available treatment that has shown any success is the use of dopamine antagonists, but the efficacy of this treatment is reduced with the disease's inexorable progression.


Effective treatment seems to be impossible without identifying and understanding the defective gene which causes Huntington’s disease. Such knowledge could allow affected foetuses to be identified, but there are obvious ethical issues here. There has however, been speculation that the tissue degeneration could be caused by the production of a toxin within the striatum, or its connected structures. One possible chemical could be quinolinic acid, which is produced in human brains. External toxins have also been suggested. Kanic acid, which kills cells, has been found to replicate the chemical changes seen in Huntington's when injected into rat striatum, but nothing more. There is also the possibility of excess glutamaic acid causing the cataclysmic over-stimulation of cells. If this is so, the blocking of striatal NMDA receptors may prove a successful treatment.


As with many degenerative brain conditions, there is no current cure, and certianly no greatly effective treatment can be provided until the aetiology of the condition has been fully understood.


"Brain, Biochemestry and Brain Disorders", P. G. Strange, Oxford University Press, 1992

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