Potential Usage of Acetylcholine Muscarinic 1 Receptor Agonist to Manage Parkinson Disease
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on April 2nd, 2025
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Acetylcholine deficiency is linked to Parkinson’s disease and has been associated with increased stride time variability and a higher risk of falls. Normally, acetylcholine is released into the synaptic cleft to activate neighboring neurons, and its signaling is terminated by acetylcholinesterase, which degrades the neurotransmitter. However, acetylcholinesterase inhibitors have not reduced the disease burden and often lead to unacceptable side effects. To address this, a study funded by Takeda Pharmaceutical was conducted to assess TAK-071, a novel muscarinic acetylcholine 1 receptor agonist, for managing Parkinson’s disease.
The phase 2 clinical trial enrolled 54 participants, with an average age of 69.7 years, who were diagnosed with Parkinson’s disease according to the Movement Disorders Society criteria. Gait variability was assessed using a mobile device that monitored stride time variability during a natural-paced 2-minute walk. Participants were randomly assigned to receive either an oral placebo or TAK-071, with a daily dose of 7.5 mg for those aged 40 to 65 and 5.0 mg for those aged 66 to 85. After 6 weeks of treatment, researchers found that TAK-071 did not prevent motor dysfunction progression, as there was no difference in stride time variability between the placebo and treatment groups. However, TAK-071 appeared to slow cognitive decline, particularly in maintaining executive function. The authors suggested that future studies should also investigate agonists targeting nicotinic α4β2 acetylcholine receptors, which are widely expressed in the brainstem.
The phase 2 clinical trial enrolled 54 participants, with an average age of 69.7 years, who were diagnosed with Parkinson’s disease according to the Movement Disorders Society criteria. Gait variability was assessed using a mobile device that monitored stride time variability during a natural-paced 2-minute walk. Participants were randomly assigned to receive either an oral placebo or TAK-071, with a daily dose of 7.5 mg for those aged 40 to 65 and 5.0 mg for those aged 66 to 85. After 6 weeks of treatment, researchers found that TAK-071 did not prevent motor dysfunction progression, as there was no difference in stride time variability between the placebo and treatment groups. However, TAK-071 appeared to slow cognitive decline, particularly in maintaining executive function. The authors suggested that future studies should also investigate agonists targeting nicotinic α4β2 acetylcholine receptors, which are widely expressed in the brainstem.