Nigrostriatal blood-brain barrier opening in Parkinson's disease

The Opening of the Blood-Brain Barrier in the Nigrostriatal System in Parkinson’s Disease

Research Background

Parkinson’s disease is a neurodegenerative disorder characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to impaired dopaminergic transmission in the striatum. Currently, there are no effective treatments to halt or reverse the progression of the disease. Potential therapeutic approaches, such as drug molecules and gene therapies, face challenges in crossing the blood-brain barrier (BBB) to reach relevant brain areas. This study aims to evaluate the safety, feasibility, and tissue permeability of opening the BBB in the substantia nigra and striatum regions of Parkinson’s disease patients using magnetic resonance-guided focused ultrasound (MRgFUS) technology.

Research Institutions and Authors

This study was conducted by Carmen Gasca-Salas and numerous researchers from the HM Clinical Neuroscience Center in Madrid, Spain, and was published online in 2024 in the prestigious international neurology journal, Journal of Neurology, Neurosurgery & Psychiatry.

Research Process

The study included 3 Parkinson’s disease patients with mild cognitive impairment or dementia. The MRgFUS technique was used to open the BBB in the right substantia nigra and posterior striatum regions of the patients. Two of the patients underwent a second BBB opening procedure 2-3 weeks after the initial treatment, followed immediately by 18F-Choline positron emission tomography (PET) scans. Researchers meticulously monitored and recorded various parameters throughout the MRgFUS process. The status of the BBB was evaluated using enhanced MRI sequences at baseline, 24 hours, 14 days, and 3 months post-treatment. Clinical symptom changes in the patients were also closely monitored.

Main Findings

1. The BBB was successfully opened synchronously in the substantia nigra and striatum on the same side in all 3 patients, with no severe adverse reactions.
2. Some patients showed signs of BBB opening 24 hours post-treatment, but the BBB was completely closed by 14 days post-treatment.
3. 18F-Choline PET scans in two patients indicated a significant increase in radiotracer uptake in the opened areas, suggesting that BBB opening allowed drug penetration into the brain parenchyma.
4. MRI sequences in individual patients showed small patchy T2* hypointense signals, which could indicate microbleeds, although there were no clinical symptoms observed.
5. After a 3-month follow-up, there were no significant changes in patients’ motor and non-motor symptoms.

Research Significance

This study preliminarily demonstrates that MRgFUS technology can safely and feasibly achieve BBB opening in the nigrostriatal system, allowing drug penetration into relevant brain regions. This minimally invasive technique offers a potential targeted drug delivery approach for early-stage Parkinson’s disease, holding significant clinical application prospects. Future studies need to increase the sample size to further evaluate the efficacy and safety of the technique and conduct related therapeutic trials.

Research Highlights

1. This is the first study to synchronously achieve BBB opening in the two key pathological regions of Parkinson’s disease: the substantia nigra and striatum.
2. PET imaging directly confirmed drug entry into the brain parenchyma following BBB opening.
3. Comprehensive multimodal imaging evaluation monitored BBB opening and clinical symptom changes.
4. Systematic assessment of the safety and feasibility of this new technology in Parkinson’s disease patients.