InBrain Pharma publishes article on L-DOPA limitations in Parkinson's management

InBrain Pharma, a company specializing in the treatment of neurodegenerative diseases, has announced the publication of a new article in the Journal of Parkinson's Disease. The article, titled "Effectiveness of Continuous Dopaminergic Therapies in Parkinson's Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics," addresses the pharmacokinetic and pharmacodynamic challenges associated with the use of L-DOPA in treating Parkinson's disease. The publication, dated July 2024, examines the limitations of L-DOPA, a common treatment for Parkinson's, particularly when used for continuous dopaminergic stimulation, and underscores the need for new therapeutic approaches.

Parkinson's disease is marked by a deficiency of dopamine in the brain. Since dopamine itself cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), is used as the primary treatment. However, L-DOPA has significant pharmacokinetic and pharmacodynamic challenges that become more pronounced as the disease progresses. These issues contribute to both motor and non-motor complications after a few years of treatment, prompting the development of continuous dopaminergic stimulation therapies. Unfortunately, these therapies have not fully addressed the limitations of L-DOPA.

The article reviewed ten of the most relevant studies in existing literature. The findings highlight various pharmacokinetic and pharmacodynamic issues with L-DOPA, including limited digestive and cerebral passage, peripheral distribution, short half-life, and age-related declines in central aromatic L-amino acid decarboxylase. Additionally, problems such as poor distribution in many cells and pulsatile stimulation of dopaminergic receptors were noted. Current treatments beyond oral L-DOPA have not effectively resolved these challenges.

Professor Caroline Moreau, a neurologist at Lille University Hospital and co-founder of InBrain Pharma, emphasized the importance of the new data. "Many of L-DOPA's pharmacokinetic and pharmacodynamic constraints are not resolved by existing subcutaneous or enteral continuous dopaminergic stimulation therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation. Medical needs in the management of Parkinson's disease remain very great."

In response to these unmet needs, InBrain Pharma has developed a new treatment, A-dopamine, administered via the intracerebroventricular (i.c.v.) route. This treatment aims to provide continuous personalized delivery of dopamine to patients with advanced Parkinson's disease who experience severe complications that are refractory to L-DOPA treatment. According to Professor David Devos, another co-founder of InBrain Pharma, this treatment has shown promising results. "A-dopamine treatment considerably reduced the periods during which patients suffered from dopamine-dependent tremors, slowness, pain, and difficulty walking and communicating, as well as L-dopa-induced abnormal symptoms like involuntary movements and agitation," he stated.

Preliminary results from the DIVE-I phase I/II clinical trial, conducted in collaboration with Lille University Hospital, have confirmed the treatment's excellent ergonomics, high safety profile, and significant clinical effect in controlling severe motor symptoms. This has enabled a reduction in the dosage of underlying oral L-DOPA-based treatments.

The final results of the DIVE-I clinical trial are set to be announced at the International Congress of Parkinson's Disease and Movement Disorders in Philadelphia at the end of September 2024. This new therapeutic modality is expected to change the treatment paradigm for Parkinson's disease and other neurodegenerative diseases, paving the way for precision medicine in neurology.