Efficacy of Oral Administration of Trehalose in Patients With Parkinson Disease
Status:
Not yet recruiting
Trial end date:
2023-05-01
Target enrollment:
Participant gender:
Summary
Parkinson's disease (PD) is a neurodegenerative disease characterized by the
neurodegeneration of substance nigra pars compacta (SNpc) and the formation of
alpha-synuclein protein aggregates in neurons. Although most PD patients are sporadic, it is
now clear that genetic factors contribute to the pathogenesis of PD. Indeed, LRRK2 G2019S
mutation is one of the most common causes of familial PD. The phenotype corresponding to this
mutation is a late-onset form of PD characterized by the accumulation of the N-ethylmaleimide
sensitive factor (NSF) in neurons. It is due to a dysfunction of the physiological autophagy
processes occurring at cellular level, mainly affecting autophagy mediated by chaperone
proteins (Chaperon Mediated Autophagy, CMA), responsible for the clearance of alpha synuclein
at the lysosomal level. This condition, although sensitive to treatment with L-DOPA and
dopamine agonists, does not currently have any specific therapy.
Recently, in a mouse model carrying the LRRK2 mutation, it has been demonstrated that
treatment with trehalose is able to reduce the accumulation of NSF deposits in neurons of
various brain areas such as the substantia nigra, striatum, cortex and hippocampus. The
reduction of protein aggregates correlates with intracellular molecules related to the
activation of apoptotic processes in damaged neurons. Moreover, it has been found a
significant improvement in motor and cognitive performance. The aim of the present study is
to evaluate the safety and tolerability of trehalose in two groups of patients affected by
idiopathic PD and PD carrying the LRRK2 mutation, respectively. Moreover, the investigators
will collect preliminary data on the effect that this molecule potentially has on disease
course in both groups. The treatment duration will be 24 weeks and the overall study duration
approximately 12 months. The populations observed will be composed of subjects affected by
idiopathic PD and familial PD carrying the genetically confirmed LRRK2 mutation. Enrolled
subjects will daily take trehalose in oral administration. Safety will be assessed by
detecting any adverse events and analyzing blood chemistry parameters. The effect of
trehalose will be evaluated through periodic clinical examinations, including the
administration of specific scales and questionnaires.