Gene Therapy Breakthrough in Parkinson’s Disease


Key Points

  • A preclinical study led by Prof. José Obeso used focused ultrasound plus microbubbles to deliver gene therapy across the blood-brain barrier (BBB).
  • Gene therapy has incredible potential to prevent, stop, or treat Parkinson’s disease.
  • The gene therapy reached the target areas, and BBB opening was temporary, safe, and well tolerated.

BBB Opening with Focused Ultrasound in Nonhuman Primates and Parkinson’s Disease Patients: Targeted AAV Vector Delivery and PET Imaging

In vivo PET imaging of BBB permeability using 18F-Choline in NHPs and patients with PD.
Source: Javier Blesa et al., BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging.Sci. Adv.9,eadf4888(2023).DOI:10.1126/sciadv.adf4888

A Parkinson’s disease (PD) study partially funded by the Foundation and led by Prof. José Obeso at HM CINAC in Madrid, Spain, used focused ultrasound plus microbubbles to deliver gene therapy safely and efficiently across the blood-brain barrier (BBB) to two regions of the brain affected by PD. Gene therapy has incredible potential to treat PD, because it could be used in three different ways: to stop the degenerative process, restore damaged neurons, or protect undamaged neurons.

The researchers proved that they could deliver modified adeno-associated virus (AAV) serotype 9 vectors to the putamen and mid brain regions of the brain in six non-human primates using Insightec’s Exablate Neuro MR-guided focused ultrasound device and Lantheus Medical Imaging’s Luminity microbubbles. They began the low-intensity pulsed sonications to open the BBB three to four minutes after administering the microbubbles through an MRI-compatible infusion pump. The AAV9 vectors were administered intravenously after BBB opening had been achieved.

The group found the BBB openings to be temporary, safe, and well tolerated by the primates. Fluorescent proteins tagged onto the AAV9 vectors confirmed delivery into the targeted regions of the brain.

A previous study used 18F-choline PET imaging in three human participants with PD dementia to demonstrate the ability of focused ultrasound to successfully open the BBB in the putamen and midbrain and allow for the delivery of large molecules that would otherwise not cross the BBB without focused ultrasound.

In an interview with the Spanish newspaper El País, Prof. Obeso said, “Our ultimate goal is to treat neurological diseases, such as Parkinson’s, early and noninvasively… If all goes well, we could start testing on patients in the summer of 2024.”

See Science Advances (Open Access)

See the Article in El País

See Coverage from The Daily Beast

See Commentary in Nature Reviews Neurology

Sneaking Past the Blood-Brain Barrier to Usher in the Age of Gene Therapy for Neurodegenerative Disease | Medical XPress