Genetic screening in Parkinson*s Disease in order to identify patients who can participate in clinical trials with new targeted therapies

For the upcoming Phase 1B study (CHDR1710), investigating a possible
first-in-class disease modifying drug, 28 Parkinson*s disease patients with a
GBA1 mutation (PD-GBA+) are needed. This is a mutation that occurs in
approximately 5-10% of PD patients. There is no way to phenotypically
differentiate between PD patients with and without a GBA1 mutation. In order to
identify these patients, a large-scale screening is needed.
Another gene which is known to be involved in the Parkinson*s disease process
is the LRRK2 gene. This gene is also a possible target for novel treatments,
currently being investigated. In order to perform proof-of-concept or efficacy
studies of such treatments, a database of genotyped PD patients is important in
order to be able to efficiently enroll a relevant subject population.

* Genotyping of the full GBA1 gene in people with Parkinson*s Disease, assessed
as wildtype (GBA-) or containing a mutation (GBA+); the specific mutation will
be recorded as well.
* Assessing the presence of 7 known PD-causing mutations in the LRRK2 gene in
people with Parkinson*s Disease, assessed as wildtype (LRRK2-) or containing a
mutation (LRRK2+); the specific mutation will be recorded as well.
* Storage of DNA, obtained through saliva, for possible further assessments of
genes related to Parkinson*s Disease in the future.

The screening of the GBA1 and LRRK2 gene in people with Parkinson*s disease
will take place by means of saliva sampling. This can be provided at home
through a special saliva kit, which can be returned by mail. Patients will be
approached by their treating neurologist by letter with a referral to CHDR if
they wish to participate. After the patient has contacted CHDR, a letter with
additional information and a saliva kit will be sent to their home. The
received saliva will be genotyped at GenomeScan laboratory. Patients with a
GBA1 mutation will be contacted to participate in the planned Phase 1B study
(CHDR1710). This design will allow a large-scale, non-invasive screening of PD
patients with a low patient burden.

This study concerns genetic screening of Parkinson*s patients to identify those
with a GBA1 or LRRK2 mutation. 28 Parkinson*s patients are needed the planned
Phase 1B study (CHDR1710) where a possible first-in-class disease modifying
drug LTI-291 will be investigated. Similarly, selective LRRK2 kinase inhibitors
are being developed and several are about to enter the clinical phase of drug
development. To obtain these 28 Parkinson's patients with a GBA1 mutation and
to identify patients with a LRRK2 mutation, Parkinson's patients will be
approached to donate a saliva sample (an at home kit) to screen the GBA1 and
LRRK2 genes. This is a low risk procedure and the burden is minimal.