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result sql = Prion diseases: current understanding of epidemiology and pathogenesis, and therapeutic advances.
Prion diseases: current understanding of epidemiology and pathogenesis, and therapeutic advances.
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char = l;code = 108
char = l;code = 108
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = o;code = 111
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = y;code = 121
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;;code = 59
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = v;code = 118
char = C;code = 67
char = J;code = 74
char = D;code = 68
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = 9;code = 57
char = 9;code = 57
char = 4;code = 52
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = a;code = 97
char = k;code = 107
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 0;code = 48
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = D;code = 68
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = 2;code = 50
char = 0;code = 48
char = 0;code = 48
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = 8;code = 56
char = 3;code = 51
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = b;code = 98
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = v;code = 118
char = C;code = 67
char = J;code = 74
char = D;code = 68
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = o;code = 111
char = r;code = 114
char = l;code = 108
char = d;code = 100
char = w;code = 119
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = r;code = 114
char = P;code = 80
char = (;code = 40
char = c;code = 99
char = );code = 41
char = );code = 41
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = P;code = 80
char = r;code = 114
char = P;code = 80
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = r;code = 114
char = P;code = 80
char = (;code = 40
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = );code = 41
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = r;code = 114
char = P;code = 80
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = r;code = 114
char = P;code = 80
char = (;code = 40
char = s;code = 115
char = c;code = 99
char = );code = 41
char = );code = 41
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = P;code = 80
char = r;code = 114
char = P;code = 80
char = (;code = 40
char = s;code = 115
char = c;code = 99
char = );code = 41
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = v;code = 118
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = u;code = 117
char = t;code = 116
char = -;code = 45
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = T;code = 84
char = S;code = 83
char = E;code = 69
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = e;code = 101
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = a;code = 97
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = v;code = 118
char = C;code = 67
char = J;code = 74
char = D;code = 68
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = P;code = 80
char = r;code = 114
char = P;code = 80
char = (;code = 40
char = s;code = 115
char = c;code = 99
char = );code = 41
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = d;code = 100
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result sql = The bovine spongiform encephalopathy (BSE) epidemic, along with the related threat to human health posed by the transmission of the BSE agent to humans, has highlighted the importance of prion diseases. These fatal neurodegenerative diseases are characterised by spongiform changes in the CNS, and comprise a wide spectrum of clinicopathological entities in humans and animals, such as Creutzfeldt-Jakob disease (CJD) and its emerging new variant (vCJD) in humans, and BSE and scrapie in animals. This article reviews the geographical distribution and the temporal trends of CJD and vCJD; the major events in the pathogenesis of prion diseases; the risk factors for sporadic CJD and vCJD; and the possible strategies for treating them. Worldwide statistics indicate that sporadic CJD has a stable incidence of one case per million people per year; in contrast, the incidence of vCJD appears to have increased exponentially from its characterisation in 1994 to a peak in 2000. As of December 2005, 183 definite or probable cases of vCJD had been reported worldwide. The crucial event in the pathogenesis of prion diseases is the conversion of the normally occurring cellular prion protein (PrP(c)) into a pathogenic form, called protease-resistant PrP (PrP(res)) or scrapie PrP (PrP(sc)). Pathogenetic studies in rodent models have shown that PrP(sc) is found in the enteric nervous system and in the gut-associated lymphoid tissue following oral scrapie ingestion. The role of the lymphoreticular system in the pathogenesis of TSE seems to be related to the strains of agents and the host genotype. Therapeutic approaches to vCJD are mainly based on the inhibition or prevention of the pathological change that creates PrP(sc). Derivatives of acridine (such as mepacrine [quinacrine]) and the phenothiazine psychotropics have been proposed as possible therapies because of their activity in cellular models; however, neither class was able to affect the protease resistance of preexisting PrP fibrils. More encouragingly, in animal models of prion disease, tetracyclines were found to reduce prion infectivity by direct inactivation of PrP(sc). While these findings are promising, the suitability of these compounds for clinical use is still limited by their low efficacy once symptoms are apparent. Treatments based on the vaccination approach have also produced positive results, but further investigations are necessary to establish their clinical application.

Publication: CNS Drugs 2006 ;20(1)::15-28.
Publication Date: 2006
Study Author(s): Caramelli, Maria;Ru, Giuseppe;Acutis, Pierluigi;Forloni, Gianluigi;
Institution: CEA-National TSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy.
Shortcut link to this study:
The bovine spongiform encephalopathy (BSE) epidemic, along with the related threat to human health posed by the transmission of the BSE agent to humans, has highlighted the importance of prion diseases. These fatal neurodegenerative diseases are characterised by spongiform changes in the CNS, and comprise a wide spectrum of clinicopathological entities in humans and animals, such as Creutzfeldt-Jakob disease (CJD) and its emerging new variant (vCJD) in humans, and BSE and scrapie in animals. This article reviews the geographical distribution and the temporal trends of CJD and vCJD; the major events in the pathogenesis of prion diseases; the risk factors for sporadic CJD and vCJD; and the possible strategies for treating them. Worldwide statistics indicate that sporadic CJD has a stable incidence of one case per million people per year; in contrast, the incidence of vCJD appears to have increased exponentially from its characterisation in 1994 to a peak in 2000. As of December 2005, 183 definite or probable cases of vCJD had been reported worldwide. The crucial event in the pathogenesis of prion diseases is the conversion of the normally occurring cellular prion protein (PrP(c)) into a pathogenic form, called protease-resistant PrP (PrP(res)) or scrapie PrP (PrP(sc)). Pathogenetic studies in rodent models have shown that PrP(sc) is found in the enteric nervous system and in the gut-associated lymphoid tissue following oral scrapie ingestion. The role of the lymphoreticular system in the pathogenesis of TSE seems to be related to the strains of agents and the host genotype. Therapeutic approaches to vCJD are mainly based on the inhibition or prevention of the pathological change that creates PrP(sc). Derivatives of acridine (such as mepacrine [quinacrine]) and the phenothiazine psychotropics have been proposed as possible therapies because of their activity in cellular models; however, neither class was able to affect the protease resistance of preexisting PrP fibrils. More encouragingly, in animal models of prion disease, tetracyclines were found to reduce prion infectivity by direct inactivation of PrP(sc). While these findings are promising, the suitability of these compounds for clinical use is still limited by their low efficacy once symptoms are apparent. Treatments based on the vaccination approach have also produced positive results, but further investigations are necessary to establish their clinical application.
PMID: 16396521

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