Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-04-30
2003-06-03
Spivack, Phyllis G. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06573276
ABSTRACT:
The invention relates to the use of the functionally selective muscarinic M1 agonist talsaclidine for the preparation of a medicament for inhibiting &bgr;-amyloid synthesis and reduction in synthesis of tau proteins.
BACKGROUND OF THE INVENTION
Amyloid &bgr;-peptides (A&bgr;) are strongly aggregating peptides with approximate molecular masses of 4 kDa. The predominant forms, A&bgr;
40
and A&bgr;
42
, are 40 and 42 amino acid residues in length, and are the major proteinaceous constituents of brain amyloid deposits in a variety of diseases. A&bgr;
42
is an early and central component of amyloid in diffuse and senile plaques, while A&bgr;
40
is the major peptide form in amyloid deposits in the cerebral microvasculature. A&bgr;
40
and A&bgr;
42
are derived by endoproteaolysis of the larger amyloid precursor protein (APP) by the combined activities of &bgr;-secretases that cleaves at the amino-terminus, and a &ggr;-secretase that cleaves at the C-terminus, respectively, of the A&bgr; domain. Alternative amino-terminal cleavage by &agr;-secretase within the A&bgr; domain results in the generation of non-amyloidogenic fragments. Because A&bgr; peptides readily aggregate into insoluble amyloid plaques, lowering their generation is a major objective for the design of therapeutic and preventive strategies for the treatment of a variety of diseases. Tau proteins are central to the neuropathology of, for instance, Alzheimer's disease and tau levels are increased in affected individuals.
BRIEF DESCRIPTIONS OF THE INVENTION
Surprisingly, it has been found that the selective muscarinic M1 agonist talsaclidine selectively decreases the cerebrospinal fluid (CSF) level of A&bgr;
42
, A&bgr;
40
, and tau protein; A&bgr;
40
and tau protein dose dependently. Accordingly, one embodiment of the current invention relates to the use of talsaclidine for the preparation of a medicament for lowering the level of A&bgr;
40
, A&bgr;
42
, and tau protein.
In a preferred embodiment the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment or prophylaxis of diseases associated with the formation of diffuse and senile plaques.
Furthermore, the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment or prophylaxis of diseases associated with the formation of A&bgr;
40
-, A&bgr;
42
-, and tau-containing plaques, preferably of A&bgr;
42
-containing plaques.
Moreover, the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment or prophylaxis of amyloidosis associated with the formation of A&bgr;
40
, A&bgr;
42
and tau. Preferably the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment or prophylaxis of amyloidosis associated with the formation of A&bgr;
42
.
In particular, the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment or prophylaxis of brain amyloidosis.
Furthermore, the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment or prophylaxis of vascular amyloidosis and age-related amyloidosis.
Moreover, the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment of patients suffering from mild to moderate dementia of Alzheimer-type (DAT). Patients suffering from mild to moderate dementia of Alzheimer-type show values of about 12-28, preferably 14-28 in the Mini Mental State Examination (MMSE).
Furthermore the invention relates to the use of talsaclidine for the preparation of a medicament for the prophylactic treatment of mild to moderate dementia of Alzheimer-type.
Moreover, the invention relates to the use of talsaclidine for the preparation of a medicament for the treatment of patients suffering from mild cognitive impairment (MCI) and mild age associated memory impairment (AAMI). Patients suffering from mild MCI and AAMI show values of about 23-28 in the Mini Mental State Examination (MMSE).
Furthermore the invention relates to the use of talsaclidine for the preparation of a medicament for the prophylactic treatment of mild cognitive impairment (MCI) and mild age associated memory impairment (AAMI).
REFERENCES:
Emilien et al., Archives of Neurology, 57/4 (454-45) (2000)(abstract).
Bornemann Klaus
Dorner-Ciossek Cornelia
Hock Christoph
Meier Dieter Horst
Mendla Klaus
Boehringer Ingelheim Pharma KG
Devlin Mary-Ellen
Raymond Robert P.
Spivack Phyllis G.
Witkowski Timothy X.
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