Methods and materials for detecting C9ORF72 hexanucleotide repeat expansion positive frontotemporal lobar degeneration or C9ORF72 hexanucleotide repeat expansion positive amyotrophic lateral sclerosis

9,448,232

14/162570

January 23, 2014

This document provides methods and materials for detecting C9ORF72 hexanucleotide (GGGGCC) (SEQ ID NO: 3) repeat expansion positive (C9+) frontotemporal lobar degeneration or C9+ amyotrophic lateral sclerosis. For example, methods and materials related to using anti-(GP)8 (SEQ ID NO: 2) antibodies to identify mammals (e.g., humans) having C9+ FTLD or C9+ ALS are provided.

Mayo Foundation for Medical Education and Research (Rochester, MN, US)

Mayo Foundation for Medical Education and Research (Rochester, MN, US)

1. An antibody preparation comprising anti-polyGP (Glycine-Proline) antibodies, wherein said anti-polyGP antibodies of said preparation are at least about 65 percent pure and comprise a label wherein said label is a radionuclide, fluorescent moiety, luminescent moiety, or an enzyme.

2. The preparation of claim 1 , wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 .

3. The preparation of claim 1 , wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 , and wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 4 is less than 10 3 mol −1 .

4. The preparation of claim 1 , wherein said anti-polyGP antibodies are antibodies to SEQ ID NO: 2.

5. The preparation of claim 1 , wherein said anti-polyGP antibodies of said preparation are monoclonal anti-polyGP antibodies.

6. An antibody preparation comprising an anti-polyGP (Glycine-Proline) antibody and a secondary antibody having the ability to bind to said anti-polyGP antibody, wherein said secondary antibody comprises a label, and wherein said label is a radionuclide, fluorescent moiety, luminescent moiety, or an enzyme.

7. The preparation of claim 6 , wherein the binding affinity of said anti-polyGP antibody for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 .

8. The preparation of claim 6 , wherein the binding affinity of said anti-polyGP antibody for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 , and wherein the binding affinity of said anti-polyGP antibody for a polypeptide consisting of SEQ ID NO: 4 is less than 10 3 mol −1 .

9. The preparation of claim 6 , wherein said anti-polyGP antibody is an antibody to SEQ ID NO: 4.

10. The preparation of claim 6 , wherein said anti-polyGP antibody of said preparation is a monoclonal antibody to SEQ ID NO: 2.

11. A method for making an antibody preparation comprising anti-polyGP (Glycine-Proline) antibodies, wherein said method comprises: (a) administering a polyGP polypeptide to a mammal under conditions wherein anti-polyGP antibodies are formed within said mammal, (b) purifying said anti-polyGP antibodies from said mammal to obtain said preparation, wherein said anti-polyGP antibodies of said preparation are at least about 65 percent pure, and (c) labeling said anti-polyGP antibodies of said preparation with a label, wherein said label is a radionuclide, fluorescent moiety, luminescent moiety, or an enzyme.

12. The method of claim 11 , wherein said mammal is a mouse.

13. The method of claim 11 , wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 .

14. The method of claim 11 , wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 , and wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 4 is less than 10 3 mol −1 .

15. A method for making an antibody preparation comprising anti-polyGP (Glycine-Proline) antibodies, wherein said method comprises: (a) culturing hybridoma cells to form supernatant comprising anti-polyGP antibodies, (b) harvesting anti-polyGP antibodies from said supernatant to form said preparation, wherein said anti-polyGP antibodies of said preparation are at least about 65 percent pure, and (c) labeling said anti-polyGP antibodies of said preparation with a label, wherein said label is a radionuclide, fluorescent moiety, luminescent moiety, or an enzyme.

16. The method of claim 15 , wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 .

17. The method of claim 15 , wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 2 is between 10 6 mol −1 and 10 12 mol −1 , and wherein the binding affinity of said anti-polyGP antibodies for a polypeptide consisting of SEQ ID NO: 4 is less than 10 3 mol −1 .

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