org-2766 and Alzheimer-Disease

Clinical studies of cognitive effects of ACTH fragments carried out so far with ACTH (1-10) and (4-9) (Org. 2766) brought about inconsistent and partly disappointing results. Efficacy could not be demonstrated in patients with Alzheimer's disease (AD). A possible reason for these results is the low metabolic stability and low lipophilicity of these compounds. HOE 427 has a considerably prolonged metabolic stability, has a high lipophilicity, and is much more potent than are existing compounds in pharmacologic models of memory and learning. It also was proven to have significant effects on ACh metabolism. Single dose studies in groups of mildly cognitively impaired elderly subjects and in patients with AD showed slight but significant effects on attention and mood. The effects were less consistent in patients than in healthy subjects.

Topics: Adrenocorticotropic Hormone; Affect; Alzheimer Disease; Animals; Cognition; Double-Blind Method; Humans; Peptide Fragments; Rats

Topics: Adrenocorticotropic Hormone; Alzheimer Disease; Choline; Dementia; Dihydroergotoxine; Humans; Narcotic Antagonists; Peptide Fragments; Phosphatidylcholines; Physostigmine; Piracetam; Pyrrolidines; Succinimides

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Amino Acid Sequence; Behavior; Cognition; Double-Blind Method; Female; Humans; Male; Middle Aged; Molecular Sequence Data; Peptide Fragments; Psychological Tests; Reaction Time

Clinical studies of cognitive effects of ACTH fragments carried out so far with ACTH (1-10) and (4-9) (Org. 2766) brought about inconsistent and partly disappointing results. Efficacy could not be demonstrated in patients with Alzheimer's disease (AD). A possible reason for these results is the low metabolic stability and low lipophilicity of these compounds. HOE 427 has a considerably prolonged metabolic stability, has a high lipophilicity, and is much more potent than are existing compounds in pharmacologic models of memory and learning. It also was proven to have significant effects on ACh metabolism. Single dose studies in groups of mildly cognitively impaired elderly subjects and in patients with AD showed slight but significant effects on attention and mood. The effects were less consistent in patients than in healthy subjects.

Topics: Adrenocorticotropic Hormone; Affect; Alzheimer Disease; Animals; Cognition; Double-Blind Method; Humans; Peptide Fragments; Rats

Seventy-seven patients with Alzheimer's disease were submitted to a double-blind no cross-over study of the effect of a synthetic ACTH4-9 analog (Org 2766) on the EEG. The quantitative EEG power spectrum analysis with 22 Org 2766 and 22 placebo treated patients showed no improvement which could be related to the Org 2766 medication (6 months, 40 mg daily), either comparing the successive EEG sessions or comparing the drug treated group with the placebo treated group. The placebo treated group showed a decrease of power in the beta band after 4 and 6 months and an increase of theta after 6 months, which is regarded as a sign of deterioration of the EEG in advancing disease. These changes did not occur in the Org 2766 treated group. However, a subgroup analysis of 9 Org 2766 treated patients and 9 placebo treated patients without other CNS drugs during the study did not reveal consistent differences between the groups after 4 and 6 months of therapy. We believe that Org 2766 does not have a long-term protecting effect on the EEG.

Topics: Adrenocorticotropic Hormone; Alpha Rhythm; Alzheimer Disease; Clinical Trials as Topic; Double-Blind Method; Electroencephalography; Humans; Peptide Fragments

In a double-blind, placebo-controlled study, the central nervous system effects of an ACTH4-9 analog, Org2766 (40 mg/day), in Alzheimer's disease were assessed by measuring cerebrospinal fluid parameters during 6 months' treatment. Somatostatin-like immunoreactivity and cholinesterase activity, which are known to be reduced in cerebrospinal fluid of Alzheimer patients compared with controls, did not change during treatment. As a marker of noradrenergic and dopaminergic systems, we measured dopamine-beta-hydroxylase and homovanillic acid, but both levels were static. These results suggest that Org2766 did not interact with the transmitter systems, which are thought to be disturbed in Alzheimer's disease.

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Cholinesterases; Cyclic AMP; Dopamine beta-Hydroxylase; Double-Blind Method; Female; Homovanillic Acid; Humans; Male; Middle Aged; Peptide Fragments; Peptides

The synthetic ACTH 4-9 analog, Org 2766, was administered to 77 Alzheimer's patients for 6 months in a double-blind, placebo-controlled study. Although Org 2766 was tolerated well, no significant effect of Org 2766 could be demonstrated in terms of rating scales or cognitive functions.

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Peptide Fragments; Placebos