Genetic screening in Parkinson*s disease patients to identify GBA1 mutation carriers for future clinical trials.

Parkinson*s disease (PD) is a common neurodegenerative disease, present in 1-2%
of individuals aged >= 65 years. The most common genetic risk factor for
Parkinson*s disease is a heterozygous mutation in the GBA1 gene. In a previous
study it was demonstrated that 15% of Parkinson*s disease patients in the
Netherlands have a mutation in the GBA1 gene. GBA1 encodes for
beta-glucocerebrosidase (GCase), a lysosomal enzyme that is responsible for the
hydrolysis of the glucosylceramide to ceramide and glucose. A mutation in GBA1
causes lysosomal dysfunction and it is hypothesized that this eventually leads
to accumulation of alpha synuclein which is the hallmark of PD. PD patients
with a mutation in the GBA1 gene exhibit an earlier onset of disease and have
an increased risk of cognitive decline but can otherwise not be differentiated
from idiopathic PD patients based on phenotype.

For an upcoming Phase 1b trial investigating a potential disease modifying
therapy in the form of a GCase activator (VQ101) developed by Vanqua Bio, we
aim to identify potential study participants with a mutation in the GBA1 gene.
To identify this group of PD patients, a large screening study will be
conducted.

To sequence the GBA1 gene in Parkinson*s disease patients to identify possible
participants for a possible future phase 1 trial. The gene will be described as
wildtype (WT) or containing a mutation (GBA+); with record of the specific
mutation.


To store DNA, obtained from a saliva sample, for possible further assessments
of genes related to Parkinson*s disease in the future. (DNA is only stored if
participant consents to optional storage)

The genetic screening for mutations in the GBA1 gene will be performed through
saliva sampling. Samples will be taken by Parkinson*s disease patients at home
with a saliva sampling kit that will be sent to them via mail by CHDR staff.
Subjects will also receive a questionnaire composed of two questions
(ethnicity, familial Parkinson's disease history).

Awareness for the study will be raised in collaboration with the treating
neurologists of the PD patients and through advertisement by CHDR via (social)
media.

If a patient contacts the CHDR and wishes to participate, an informed consent
document will be provided via mail. Once a completed ICF is obtained by CHDR,
the saliva kit and a questionnaire will be sent by CHDR to the patient. The
saliva sample will be labelled with a subject specific code to ensure sample
pseudonymization. Only CHDR has the code to link the saliva sample to the
patient. Saliva samples will thereafter be sent to the laboratory of GenomeScan
for sequencing. All patients will be informed on the result of the sequencing
and offered further counselling if applicable. This counselling can be done
either via CHDR or via the treating neurologist at the local hospital if
preferred.

This study requires a saliva sampling and a questionnaire. The procedure for
this is with a saliva sampling kit which can be performed at home. The kits can
be returned by mail. The burden for patients is minimal and there are no risks
associated with the procedure.