A Trial to Determine the Safety and Tolerability of Transplanted Stem Cell Derived Dopamine Neurons to the Brains of Individuals With Parkinson's Disease

Inclusion Criteria:

• Have given written informed consent to participate in the trial

• Diagnosed with PD as defined using Queens Square Brain Bank criteria

• Moderate disease as defined by having Hoehn and Yahr stage 2-3 in OFF state

• Disease duration > 10 years

• Male or female, aged between 50 and 75 years (inclusive)

• Have a significant response to dopamine therapies as judged by the PI or otherdelegated clinician

• Have symptoms that are not appropriately controlled by existing oral anti-PDmedications, as judged by the PI or other delegated clinician

• Ability to travel to Lund for surgery

• Followed up for at least 12 months prior to inclusion in this trial in the TransEUroobservational study

• Be fluent in English/Swedish to enable completion of questionnaires as assessed bythe PI or other delegated clinician at Cambridge/Lund, respectively

• Be approved by the TMG clinical sub-group for trial participation

Exclusion Criteria:

• Tremor dominant disease, as assessed by the PI or other delegated clinician

• Significant drug induced dyskinesias as defined by a score of > 2 in the AbnormalInvoluntary Movement Scale (AIMS) dyskinesias rating scale, in any body part in theON state

• Ongoing major medical or psychiatric disorders, including depression (MADRS > 20)and psychosis, that make participation unsuitable, as judged by the PI or otherdelegated clinician

• Any contraindication to neurosurgery

• Unable to be imaged using MRI

• Extensive ventral striatal loss or normal findings on F-DOPA PET at screening

• Significant cognitive impairment indicative of an incipient dementia/establisheddementia or values consistent with MoCA score of ≤ 24

• Unable to perform normal copying of interlocking pentagons and/or a semantic fluencyscore for naming animals of less than 20 over 90 seconds

• Other concomitant treatment with neuroleptics (including atypical neuroleptics)and/or cholinesterase inhibitors

• Previous neurosurgery to the brain, or cell or organ transplantation, or recipientof repeated blood transfusions

• Any contraindication to immunosuppressive therapy, prophylactic antibiotics, and/orosteoporosis prophylaxis (refer to STEM-PD Trial Immunosuppressant Manual)

• High levels of pre-formed specific anti-HLA antibodies to the cell product

• Severely reduced TPMT activity (less than half of the lower normal TPMT activitylevel)

• History of documented severe/significant allergy requiring treatment

• Female who is pregnant or breastfeeding

• Received an investigational drug (including investigational vaccines) or used aninvasive investigational medical device within 4 weeks of the screening visit, or iscurrently enrolled in an interventional investigational trial

• Female of childbearing potential or male unwilling to follow contraceptionrequirements (see protocol section 12.15)

• Any other condition which, in the opinion of the investigator, makes the patientinappropriate for entry into the trial