Ambroxol as a Disease-modifying Treatment in GBA-PD

Prior treatment

• Any clinically significant or unstable medical condition, which, in the opinion of the principal investigator or the clinician delegated by the principal investigator, may put the participant at risk when participating in the study (e.g. previous gastric/duodenal peptic ulcer, chronic obstructive pulmonary disease, severe liver or kidney changes, major cardiovascular event (e.g. myocardial infarction, decompensated congestive heart failure, pulmonary embolism occurring within 6 months prior to the screening visit), neoplastic diseases).
• Abnormalities that could preclude safe completion of the spinal cord in the investigator's opinion, including: treatment with anticoagulants; severe abnormalities or malformations of the lower spine or other spinal disorders; bleeding diathesis (e.g. clinically significant coagulopathies or thrombocytopenia); hypersensitivity to lidocaine.

Other illness

• Diagnosis of Parkinson-Dementia (MDS Level II criteria) or other conditions that result in inability to understand and sign the informed consent
• Hoehn \& Yahr stage ≥ 4/5 in the medication-ON condition
• Known hypersensitivity to the active substance Ambroxol or to any of its excipients.

Age

• All participants of childbearing age who disagree to use double barrier or abstinence birth control while participating in the study and for 2 weeks after the last dose of study drug;

Other

• Secondary and primary atypical parkinsonism
• Deep Brain Stimulation
• Bronchial asthma
• Pregnant or breastfeeding women.

• Age 21-80 years
• Diagnosis of idiopathic PD
• Duration of motor symptoms \>5 years
• Heterozygous carrier of a GBA1 mutation.
• Capable of complying with all study procedures, including fasting lumbar puncture
• All male and female participants of childbearing age must agree with their partners to use double barrier birth control or total abstinence during study participation and for 2 weeks after the last dose of study drug.
  • Male participants who have received bilateral vasectomy are permanently sterile.
  • A woman can participate if she is of:
• Non-childbearing potential
• Women of childbearing potential must have a negative pregnancy test at the screening visit and use accepted contraceptive methods defined as highly effective.