ebiratide 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

In an acute trial, three different dosages (60, 300, and 600 micrograms) of the endocrinologically inert but behaviorally active corticotropin 4-9 (ACTH4-9) fragment ebiratide were given to three patients with clinically probable Alzheimer's disease and five patients with a major depressive episode who were psychomotorly retarded. The drug was given intravenously in a double-blind, placebo-controlled, crossover design, and cognitive as well as psychopathologic assessments were carried out predrug and postdrug treatment. In summary, no adverse effect of the ACTH fragment was detected. In this explorative study, none of the patients improved cognitively, as measured by neuropsychologic testing. However, all patients, regardless of underlying disorder, reported a decrease of the feeling of tiredness or loss of energy, respectively. They felt more vigorous and alert. This occurred after any of the three doses of ACTH4-9, but not after placebo. In concert with reports from other studies, it is concluded that the ACTH4-9 fragment ebiratide may have activating properties in humans. However, given acutely, it does not seem to have antidementia or antidepressive efficacy.

Topics: Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Alzheimer Disease; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infusions, Intravenous; Mental Status Schedule; Middle Aged; Peptide Fragments; Psychiatric Status Rating Scales

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