SYN120

SYN120 is an investigational treatment being developed by Acorda Therapeutics for Parkinson’s disease-related dementia.

How SYN120 works

The symptoms of Parkinson’s disease are caused by the progressive death of nerve cells in the brain that produce a neurotransmitter (a chemical messenger that passes signals between nerve cells) called dopamine. Dopamine is also involved in pathways to send signals from nerve cells to muscles. As a result, the symptoms of Parkinson’s disease are primarily related to motor function.

Many patients with Parkinson’s can also experience Parkinson’s-related dementia that is generally associated with a decline in memory, cognitive function, and mood. Parkinson’s-related dementia can also lead to other issues with communication, attention span, and hallucinations. One potential cause of Parkinson’s dementia is the imbalance of different neurotransmitters in the brain, such as a decrease in acetylcholine or an increase in serotonin. Serotonin binding to its receptor on brain cells can prevent the release of acetylcholine from cells resulting in a further decrease of acetylcholine signaling. Acetylcholine is essential in pathways related to memory and learning. Therefore, preventing serotonin from binding to its receptor may induce acetylcholine release.

SYN120 is a serotonin receptor antagonist, a molecule that binds to and blocks the activity of two types of serotonin receptors in the brain. It is thought that by reducing the activity of the serotonin receptors, SYN120 may reduce the symptoms of dementia in Parkinson’s patients.

SYN120 therapy is being investigated alongside other treatments that can improve acetylcholine levels, such as cholinesterase inhibitors. Cholinesterase inhibitors can block enzymes that break down the neurotransmitter acetylcholine.

SYN120 in clinical trials

A Phase 2a proof-of-concept clinical trial (NCT02258152), called SYNAPSE, aimed to evaluate the safety, tolerability, and efficacy of SYN120 in 80 people with Parkinson’s disease-associated dementia who were already receiving a stable dose of a cholinesterase inhibitor. The trial took place at 20 U.S sites and was completed in January 2018. It was supported by a grant from the Michael J Fox Foundation.

The primary objective of the trial was to assess the change in patients’ cognitive function after 16 weeks of treatment, assessed using the cognitive drug research (CDR) computerized cognition battery.

Participants were divided into two groups. Those in the first group received 20 to 100 mg doses of SYN120 four times a day, in an escalating procedure (20 mg in week 1, 50 mg in week 2, and 100 mg for the following 14 weeks), while those in the second group received placebo.

The trial included a screening period of up to six weeks, a treatment period of 16 weeks, and a safety follow-up period of two weeks.

Other information

SYN120 was originally developed by Synosia Therapeutics, but the company was later acquired by Biotie Therapies in 2011. After Acorda acquired Biotie in 2016, it gained the global rights to SYN120 and continued supporting the Phase 2a clinical trial.

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