Ppar-Gamma Agonists for Improvement of Cognitive Function in Apoe4 Negative Patients
Disclosed is a method for improving cognitive function in a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias, which subject is not homozygous for the APOE4 allele, comprising the steps of: (i) screening the subject to determine that the subject is not homozygous for the APOE4 allele; and then (ii) administering a safe and effective amount of a PPAR-gamma agonist to said subject.
1 . A method for improving cognitive function in a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias, which subject is not homozygous for the APOE4 allele, comprising the steps of:
(i) screening the subject to determine that the subject is not homozygous for the APOE4 allele; and then
(ii) administering a safe and effective amount of a PPAR-gamma agonist to said subject.
2 . A method according to claim 1 wherein screening step (i) involves determining that the subject is APOE4−.
3 . A method according to claim 1 wherein screening step (i) involves determining that the subject carries a single copy of the APOE4 allele.
4 . A method of screening a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias as an aid in predicting the subject's response to administration of a PPAR-gamma agonist, comprising screening to determine whether the subject carries zero or one copy of the APOE4 allele.
5 . A method according to claim 4 wherein the screening involves screening to determine whether the subject is APOE4−.
6 . A method according to claim 4 wherein the screening involves screening to determine whether the subject carries a single copy of the APOE4 allele.
7 . A method of improving cognitive function in a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias, which subject has been predetermined not to be homozygous for the APOE4 allele, which method comprises administering a safe and effective amount of a PPAR-gamma agonist to said subject.
8 . A PPAR-gamma agonist for use in improving cognitive function in a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias, which subject has been pre-determined not to be homozygous for the APOE4 allele.
9 - 10 . (canceled)
11 . A method, PPAR-gamma agonist or use according to claim 7 wherein the subject has been pre-determined to be APOE4−.
12 . A method, PPAR-gamma agonist or use according to claim 7 wherein the subject has been pre-determined to carry a single copy of the APOE4 allele.
13 . A method of improving cognitive function in a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias, which subject is not homozygous for the APOE4 allele, which method comprises administering a safe and effective amount of a PPAR-gamma agonist to said subject.
14 . A PPAR-gamma agonist for use in improving cognitive function in a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias, which subject is not homozygous for the APOE4 allele.
15 - 16 . (canceled)
17 . A method, PPAR-gamma agonist or use according to claim 13 wherein the subject is APOE4−.
18 . A method, PPAR-gamma agonist or use according to claim 13 wherein the subject carries a single copy of the APOE4 allele.
19 . A kit comprising (i) a PPAR-gamma agonist and (ii) instructions directing administration of the PPAR gamma agonist to a subject who is not homozygous for the APOE4 allele.
20 . A kit according to claim 19 wherein the instructions direct administration of the PPAR gamma agonist to a subject suffering from or susceptible to MCI, Alzheimer's disease or other dementias who is not homozygous for the APOE4 allele.
21 . A kit according to claim 19 wherein the subject has been pre-determined not to be homozygous for the APOE4 allele.
22 . A kit according to claim 19 wherein the subject is APOE4−.
23 . A kit according to claim 19 wherein the subject carries a single copy of the APOE4 allele.
24 . A kit according to claim 21 wherein the subject has been pre-determined to be APOE4−.
25 . A kit according to claim 21 wherein the subject has been predetermined to carry a single copy of the APOE4 allele.
26 . A method, PPAR-gamma agonist, use or kit according to claim 1 wherein the subject is suffering from MCI.
27 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the subject is suffering from Alzheimer's disease.
28 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the subject does not suffer from Type II diabetes.
29 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the subject does not suffer from Type II diabetes.
30 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the PPAR-gamma agonist is farglitazar.
31 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the PPAR-gamma agonist is a thiazolidinedione.
32 . A method, PPAR-gamma agonist, use or kit according to claim 31 , wherein the thiazolidinedione is pioglitazone.
33 . A method, PPAR-gamma agonist, use or kit according to claim 31 , wherein the thiazolidinedione is rosiglitazone.
34 . A method, PPAR-gamma agonist, use or kit according to claim 33 , wherein the rosiglitazone is in the form of rosiglitazone maleate.
35 . A method, PPAR-gamma agonist, use or kit according to claim 33 , wherein the rosiglitazone is provided at a dosage level of between 0.01 mg to 12 mg daily.
36 . A method, PPAR-gamma agonist, use or kit according to claim 35 , wherein the rosiglitazone is provided at a dosage level of 2 mg, 4 mg or 8 mg daily.
37 . A method, PPAR-gamma agonist, use or kit according to claim 35 , wherein the rosiglitazone is provided at a dosage level of 8 mg or more daily.
38 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the PPAR-gamma agonist is presented as an extended release formulation.
39 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the PPAR-gamma agonist is presented as an extended release tablet comprising a core which contains a depot of an immediate release formulation and a depot of a modified release formulation.
40 . A method, PPAR-gamma agonist, use or kit according to claim 39 wherein the tablet is surrounded by a coating through which holes penetrate; at least one penetrating to the immediate release depot and at least one penetrating to the modified release depot.
41 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the PPAR-gamma agonist is presented in a form suitable for administration as a single daily dose.
42 . A method, PPAR-gamma agonist, use or kit according to claim 1 , wherein the PPAR-gamma agonist is administered in combination with a further medicament for the treatment or prevention of Alzheimer's disease or other dementias.
43 . A method, PPAR-gamma agonist, use or kit according to claim 42 , wherein the further medicament is a cholinesterase inhibitor.
44 . A method, PPAR-gamma agonist, use or kit according to claim 43 , wherein the cholinesterase inhibitor is tacrine, galantamine, rivastigamine or donepezil.
45 . A method, PPAR-gamma agonist, use or kit according to claim 42 , wherein the further medicament is an NMDA receptor antagonist.
46 . A method, PPAR-gamma agonist, use or kit according to claim 45 , wherein the NMDA receptor antagonist is memantine.
47 . A method, PPAR-gamma agonist, use or kit according to claim 42 , wherein the further medicament is a non-steroidal anti-inflammatory drug.
48 . A method, PPAR-gamma agonist, use or kit according to claim 47 , wherein the non-steroidal anti-inflammatory drug is naproxen, ibuprofen, diclofenac, indomethacin, nabumetone, piroxicam, celecoxib or asprin.
49 . A method according to claim 1 , wherein the screening to determine that the subject is not homozygous for the APOE4 allele comprises the use of a PCR-based method.
50 . A method for improving cognitive function in a subject suffering from MCI or Alzheimer's disease, which subject is not homozygous for the APOE4 allele, comprising the steps of:
(i) screening the subject to determine that the subject is not homozygous for the APOE4 allele; and then
(ii) administering a safe and effective amount of a PPAR-gamma agonist to said subject.