A drug currently approved by the FDA for the treatment of dry mouth in Sjogren's syndrome (an autoimmune disease that affects excorine glands) has been shown to reduce levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer's patients-the first drug ever shown to have such an effect in human patients. Aβ peptide accumulates in the brain into the plaques that are a hallmark of Alzheimer's, and is a leading suspected cause of the disease. The compound AF102B, a selective activator of the M1 muscarinic receptor, blocks production of Aβ by increasing the activity of α-secretase and possibly also by inhibiting γ-secretase. The drug was therefore tested in 19 Alzheimer patients and found to reduce CSF Aβ levels by 22% in 14 patients. The drug is now in a Phase II trial that will assess its effects of cognitive status and long-term disease progression.—Hakon Heimer
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- Nitsch RM, Deng M, Tennis M, Schoenfeld D, Growdon JH. The selective muscarinic M1 agonist AF102B decreases levels of total Abeta in cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol. 2000 Dec;48(6):913-8. PubMed.