The implications of the following findings are revolutionary. The CAG count by blood sample may be vastly different than the CAG counts found in HD affected tissue. Further, one's CAG count in affected tissue may increase with age. Kennedy's disease (KD), a muscle wasting disease, is also caused by a CAG expansion. In Kennedy's disease the CAG count is further increased in muscle tissue.

We have two different disorders caused by a genetic CAG expansion in two different genes. In HD the affected cells are brain cells. In KD the affected cells are muscle cells. In both disorders the CAG count is expanded in the affected tissue beyond that measured by blood sample.

My theory, now conditionally accepted by two anonymous researchers, is that HD is an autoimmune disorder. What is 'self' may be measured by white blood cells with their stable CAG count. What is 'not self' in ever increasing degree may be the affected tissue with the age dependant expanding CAG count.

Researchers have a new challenge. How does the CAG count increase by non-replicative means and does this identify the cell as a self-antigen? A drug that reverses the age dependant CAG expansion in affected tissue may be the prize we seek. --Jerry 4Feb01

Hum Mol Genet 2000 Oct 12;9(17):2539-2544;Kennedy L,et al.

An unstable CAG triplet repeat expansion encoding a polyglutamine stretch within the ubiquitously expressed protein huntingtin is responsible for causing Huntington's disease (HD).

By quantifying the repeat sizes of individual mutant alleles in tissues derived from an accurate genetic mouse model of HD we show that the mutation becomes very unstable in striatal tissue. The expansion-biased changes increase with age, such that some striatal cells from old HD mice contain mutations that have tripled in size.

If this pattern of repeat instability is recapitulated in human striatal tissue, the concomitant increased polyglutamine load may contribute to the patterns of selective neuronal cell death in HD. Our findings also suggest that trinucleotide repeat instability can occur by mechanisms that are not replication-based.