A research team at the University of California, Irvine has discovered that a molecule called ophthalmic acid is unexpectedly acting as a neurotransmitter in the brain, similar to dopamine in regulating motor function. This discovery opens up a new therapeutic target for Parkinson’s disease and other movement disorders. The study, published in the journal Brain, found that ophthalmic acid binds to and activates calcium-sensing receptors in the brain, reversing movement impairments in Parkinson’s mouse models for more than 20 hours. This is a significant finding as existing treatments such as L-dopa only provide relief for a few hours and can lead to side effects like dyskinesia.
Parkinson’s disease is a disabling neurogenerative condition that affects millions of people worldwide, primarily those over the age of 50. Symptoms include tremors, shaking, and lack of movement, all caused by decreasing levels of dopamine in the brain as neurons die. Currently, the front-line treatment for Parkinson’s is L-dopa, which replaces lost dopamine, but its effects are short-lived, and long-term use can lead to involuntary muscle movements in patients. The discovery of ophthalmic acid as a new neurotransmitter in motor function control challenges the long-standing belief that dopamine is the exclusive neurotransmitter involved in movement regulation.
The lead researcher, Amal Alachkar, began exploring the complexities of motor function beyond dopamine more than two decades ago when she observed robust motor activity in Parkinson’s mouse models without dopamine. Through extensive metabolic examinations of brain molecules, ophthalmic acid was identified as an alternative neurotransmitter associated with motor activity in the absence of dopamine. This discovery has opened up new avenues for research and therapeutic interventions in movement disorders, particularly for Parkinson’s disease patients. The team is now working on developing products that can release ophthalmic acid in the brain or enhance the brain’s ability to synthesize it to further understand its neurological function.
The inability of neurotransmitters to cross the blood-brain barrier has been a critical hurdle in Parkinson’s treatment, which is why L-DOPA is administered to patients to be converted to dopamine in the brain. By identifying ophthalmic acid as a neurotransmitter that can potentially bypass this barrier, the research team is exploring new possibilities for more effective and long-lasting treatments for movement disorders. The study was supported by a grant from the National Institute of Neurological Disorders and Stroke and the Eric L. and Lila D. Nelson Chair in Neuropharmacology. The researchers are also named as inventors on a provisional patent covering products related to ophthalmate and calcium-sensing receptors in motor function, indicating the potential for further advancements in this area of research.