Movement disorders: magnetic resonance-guided focused ultrasound for the delivery of recombinant glucocerebrosidase to the core of Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative dyskinesia, with motor and non-motor features, caused by dopamine deficiency in the striatum, attributed to the degenerative nature of dopaminergic nerves in the substantia nigra
.
Current treatment for Parkinson's disease is primarily symptomatic, but treatments to change the condition are underway
.
However, some of the therapies under study have limited penetration into the blood-brain barrier (BBB) (e.
g.
, antibodies against α-synuclein) or use invasive neurosurgical delivery strategies (e.
g.
, convection-enhanced administration of growth factors [CED]
).

With this, Ying Meng et al.

They explored the safety and feasibility
of MRgFUS intravenous GCase at increasing doses (15 to 30 to 60 IU/kg) every 2 weeks in four PD patients with GBA1 mutations.

BBB permeability was achieved in all patients and was quantified
by dynamic contrast-enhanced magnetic resonance imaging after treatment.
No serious adverse events
occurred.

Two patients developed transient dyskinesias
after treatment.
The Blind Movement Disorders Association-Unified Parkinson's Disease Rating Scale Exercise Score decreased by 12% from baseline at 6 months (from 26±9 to 22±6).

The normalized uptake value ratio for fluorodeoxyglucose positron emission tomography of the treated shell nucleus decreased from 1.
66±0.
14 to 1.
27±0.
08
.

The significance of this study lies in the discovery of the safety and feasibility of MRgFUS GCase delivery in PD and to support further research
into this approach.