In their initial study,^[14] these investigators found that, as expected, turning the gene on produced degeneration of neurons in the mice's striatum, as occurs in people with HD. The amazing finding was that if the gene was subsequently turned off, the progression of the neurodegeneration appeared not only to stop, but also to partly reverse itself. This finding raised hopes that interfering with the abnormal HD gene in people could some day affect the course of their disease for the better.

At this year's meeting, the group from Messina, Italy, and New York City bolstered the expectation that we may in the future be able to treat HD itself, and not only its symptoms. Arancio and associates^[15] studied the strength of connections between cells in the brains of mice with the conditionally expressed HD mutation. The strength of these connections is known to increase when the connected cells are active at the same time. This strengthening, known as long-term potentiation (LTP), is likely one of the fundamental components of the biological substrate of learning and memory. The researchers found that LTP is impaired when the HD mutation is turned on, and that this impairment disappears when the mutated gene is turned off. The impairment in LTP may be part of the reason why HD patients develop cognitive deficits. If this is the case, then the fact that the LTP impairment can disappear when the gene mutation is blocked strengthens the hope that reversing HD may be possible. Based on these studies, therapies should be aimed at blocking the expression of the mutated HD gene, or interfering with the action of this gene's product (a protein known as "huntingtin").

Another study, described by Kieburtz, from Rochester, NY,^[16] was also aimed at affecting the course of HD. Because creatine has been shown to prolong survival in transgenic mice with the HD mutation, the Huntington's Study Group began a double-blind placebo-controlled study to examine the effect of 2 doses of creatine on HD patients. The investigators reported that the drug was tolerated and safe in 50 patients with HD. This was a step forward in the evaluation of this treatment for HD. The study is ongoing, and whether creatine has any beneficial effect on HD is still unknown.