METHOD FOR IDENTIFYING CRMP MODULATORS

1 . A method for identifying a modulator of CRMP suitable for prevention, alleviation and/or treatment of a CRMP-associated disease, comprising

(a) selecting a substance,

(b) contacting the selected substance with CRMP, and

(c) determining whether CRMP interacts with the substance,

wherein a substance interacting with CRMP is identified as a modulator of CRMP.

2 . The method of claim 1 , wherein CRMP comprises

(i) a polypeptide selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12 and fragments thereof, and/or

(ii) a polypeptide which is at least 70% identical to the polypeptide of (i).

3 - 5 . (canceled)

6 . The method of claim 1 , wherein the CRMP is CRMP-2.

7 . (canceled)

8 . The method of claim 1 , wherein the CRMP-associated disease is selected from neurological diseases, psychiatric diseases, inflammatory diseases, epilepsy, pain syndromes, motoneuron disorders, dyskinesias, tremor syndromes, psychoses, schizophrenia, arthritis and arthritic conditions.

9 - 14 . (canceled)

15 . The method of claim 1 , wherein the CRMP-associated disease is a CRMP-2-associated disease.

16 - 20 . (canceled)

21 . The method of claim 1 , wherein in step (b), the substance is contacted with a cell capable of expressing or overexpressing CRMP and/or with a non-human animal comprising a cell capable of expressing or overexpressing CRMP.

22 - 28 . (canceled)

29 . A cell capable of overexpressing or underexpressing CRMP and/or expressing a modified CRMP polypeptide.

30 - 31 . (canceled)

32 . A non-human animal comprising a cell capable of overexpressing or underexpressing CRMP and/or expressing a modified CRMP polypeptide.

33 . (canceled)

34 . A method for identifying a compound which is a disease-modifying compound and/or a compound suitable for neuroprotective treatment, comprising

(a) selecting a substance,

(b) contacting the selected substance with CRMP, and

(c) determining whether CRMP interacts with the substance,

wherein a substance interacting with CRMP is identified as a disease-modifying compound and/or a compound suitable for neuroprotective treatment.

35 . (canceled)

36 . The method of claim 61 , wherein the compound is lacosamide.

37 . A complex comprising CRMP and a compound of Formula (I)

wherein

R is hydrogen, alkyl, alkenyl, alkynyl, aryl, aryl alkyl, heterocyclic, heterocyclic alkyl, alkyl heterocyclic, cycloalkyl or cycloalkyl alkyl, and R is unsubstituted or is substituted with at least one electron-withdrawing group and/or at least one electron-donating group;

R 1 is hydrogen, alkyl, alkenyl, alkynyl, aryl alkyl, aryl, heterocyclic alkyl, alkyl heterocyclic, heterocyclic, cycloalkyl or cycloalkyl alkyl, and is unsubstituted or substituted with at least one electron-donating group and/or at least one electron-withdrawing group;

R 2 and R 3 are independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, aryl alkyl, aryl, halo, heterocyclic, heterocyclic alkyl, alkyl heterocyclic, cycloalkyl, cycloalkyl alkyl, or Z-Y, wherein R 2 and R 3 are each independently unsubstituted or substituted with at least one electron-withdrawing group and/or at least one electron-donating group;

Z is O, S, S(O) a , NR 4 , NR′ 6 , PR 4 or a chemical bond;

Y is hydrogen, alkyl, aryl, aryl alkyl, alkenyl, alkynyl, halo, heterocyclic, heterocyclic alkyl or alkyl heterocyclic, and is unsubstituted or substituted with at least one electron-donating group and/or at least one electron-withdrawing group, provided that when Y is halo, Z is a chemical bond, or

Z-Y taken together is NR 4 NR 5 R 7 , NR 4 OR 5 , ONR 4 R 7 , OPR 4 R 5 , PR 4 OR 5 , SNR 4 R 7 , NR 4 SR 7 , SPR 4 R 5 , PR 4 SR 7 , NR 4 PR 5 R 6 , PR 4 NR 5 R 7 , N + R 5 R 6 R 7 ,

R′ 6 is hydrogen, alkyl, or alkenyl, and is unsubstituted or substituted with at least one electron-withdrawing group and/or at least one electron-donating group;

R 4 , R 5 and R 6 are independently hydrogen, alkyl, aryl, aryl alkyl, alkenyl or alkynyl, and are each independently unsubstituted or substituted with at least one electron-withdrawing group and/or at least one electron-donating group;

R 7 is R 6 , COOR 8 , or COR 8 , and is unsubstituted or substituted with at least one electron-withdrawing group and/or at least one electron-donating group;

R 8 is hydrogen, alkyl or aryl alkyl, and is unsubstituted or substituted with at least one electron-withdrawing group and/or at least one electron-donating group;

n is 1-4; and

a is 1-3;

or a pharmaceutically acceptable salt or metabolite thereof; wherein, in the compound of Formula (I), electron-withdrawing and electron-donating groups are independently selected from halo, alkyl, alkenyl, alkynyl, nitro, carboxy, formyl, carboxyamido, aryl, guaternary ammonium, haloalkyl, aryl alkanoyl, hydroxy, alkoxy, carbalkoxy, amino, alkylamino, dialkylamino, aryloxy, mercapto, alkylthio, alkylmercapto and disulfide; and wherein the compound, or salt or metabolite thereof exhibits an affinity for CRMP characterized by a K D less than about 5 μM.

38 - 41 . (canceled)

42 . The complex of claim 37 , wherein CRMP is CRMP-2 and/or the compound of Formula (I) is lacosamide.

43 - 44 . (canceled)

45 . The cell of claim 29 , comprising a complex that comprises CRMP and a compound of Formula (I) or a pharmaceutically acceptable salt or metabolite thereof having an affinity for CRMP characterized by a K D less than about 5 μM.

46 . The non-human animal of claim 32 , wherein said cell comprises a complex comprising CRMP and a compound of Formula (I) or a pharmaceutically acceptable salt or metabolite thereof having an affinity for CRMP characterized by a K D less than about 5 μM.

47 . A method for preparing a complex of any of claim 37 , comprising contacting CRMP with a compound of Formula (I) or a pharmaceutically acceptable salt or metabolite thereof having an affinity for CRMP characterized by a K D less than about 5 μM.

48 - 52 . (canceled)

53 . A diagnostic method for a CRMP-associated disease, comprising:

(a) contacting a biological sample from a subject with a compound of Formula (I) or a pharmaceutically acceptable salt or metabolite thereof having an affinity for CRMP characterized by a K D less than about 5 μM, and thereafter

(b) assaying the biological sample for a complex comprising CRMP and the compound or salt or metabolite thereof,

wherein detection of said complex is indicative of CRMP mediation of the disease and of utility of the compound or salt or metabolite thereof in treatment of the disease.

54 - 60 . (canceled)

61 . A method for modifying disease and/or for neuroprotection in a subject, comprising administering a compound of Formula (I) or a pharmaceutically acceptable salt or metabolite thereof to the subject.