A research group has discovered that a brain molecule known as ophthalmic acid acts unexpectedly like a neurotransmitter, akin to dopamine, in controlling motor functions. This finding opens up a new area for treatment options for Parkinson’s disease and other movement disorders.
A research group from the University of California, Irvine has made a groundbreaking discovery about a brain molecule called ophthalmic acid, which surprisingly functions like a neurotransmitter similar to dopamine in the regulation of motor functions. This could lead to new treatment options for Parkinson’s disease and various movement disorders.
Published in the October edition of the journal Brain, the study shows that ophthalmic acid interacts with and activates calcium-sensing receptors in the brain, significantly reversing movement difficulties in mouse models of Parkinson’s for over 20 hours.
This debilitating neurodegenerative illness affects millions of individuals globally, particularly those over 50. Symptoms like shaking, tremors, and reduced movement arise from dwindling dopamine levels in the brain due to neuronal death. The leading treatment drug, L-dopa, compensates for the loss of dopamine but only lasts for two to three hours. Initially effective, L-dopa’s benefits diminish over time, and prolonged use can lead to dyskinesia, characterized by uncontrolled muscle movements in the patient’s face, arms, legs, and torso.
Co-corresponding author Amal Alachkar, a professor at the School of Pharmacy & Pharmaceutical Sciences, stated, “Our research presents a significant breakthrough that potentially redefines neuroscience by contesting the long-held belief that dopamine is the sole neurotransmitter responsible for motor function control. Astonishingly, ophthalmic acid not only facilitated movement but also provided benefits that far exceeded those of L-dopa in terms of duration. The discovery of the ophthalmic acid-calcium-sensing receptor pathway represents an entirely new system, paving the way for innovative research and treatments for movement disorders, particularly for Parkinson’s patients.”
Alachkar has been exploring the complexities of motor function beyond dopamine for over twenty years, having noticed significant motor activity in Parkinson’s mouse models even in the absence of dopamine. In her recent study, the team performed extensive metabolic evaluations of numerous brain molecules to determine which ones are linked to motor activity when dopamine levels are low. After comprehensive behavioral, biochemical, and pharmacological assessments, ophthalmic acid emerged as a viable alternative neurotransmitter.
“One of the major challenges in treating Parkinson’s is that neurotransmitters cannot pass through the blood-brain barrier. This is why patients are given L-DOPA, which is converted into dopamine within the brain,” Alachkar explained. “We are currently working on developing treatments that either deliver ophthalmic acid directly to the brain or boost the brain’s capability to produce it as we delve deeper into understanding the neurological role of this molecule.”
The research group also included doctoral student Sammy Alhassen, who has transitioned to a postdoctoral role at UCLA; lab specialist Derk Hogenkamp; project scientist Hung Anh Nguyen; doctoral student Saeed Al Masri; and co-corresponding author Olivier Civelli, who holds the Eric L. and Lila D. Nelson Chair in Neuropharmacology. Additionally, Geoffrey Abbott, a professor in physiology & biophysics and vice dean of basic science research at the School of Medicine, was part of the team.
This study received support from a grant awarded by the National Institute of Neurological Disorders and Stroke (grant number NS107671) and the Eric L. and Lila D. Nelson Chair in Neuropharmacology.
Alachkar and Civelli have filed a provisional patent covering inventions related to ophthalmate and calcium-sensing receptors in the context of motor function.
