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

Parkinson's disease (PD) occurs when an area of the brain begins to lose nerve cells that produce a chemical called dopamine. Dopamine is an important chemical, and one of its functions is that it helps to regulate body movement. The loss of these nerve cells leads to a reduction of dopamine in the brain. Medications used to treat PD temporarily replace this lost dopamine, but they do not repair the underlying disease. One of the most promising PD therapies to date has been the transplantation of dopamine producing cells into the brain. Unlike current treatments, these therapies may be able to repair the damage caused in PD.In this trial, the investigators will transplant a new stem cell therapy, called the STEM-PD product, into the area of the brain affected in people with PD. These stem cells can develop into many different cell types, including dopamine-producing nerve cells. The investigators will transplant the stem cells using a device that has been previously used for similar transplants in Lund. This is the first time that the STEM-PD product will be given to humans.The trial aims to assess whether the STEM-PD product is safe to use in people with PD. The investigators will also be looking for preliminary signs of efficacy.The trial will recruit participants with PD from the UK and Sweden. Eight participants will undergo the STEM-PD product transplant. Participants will receive a single dose of the STEM-PD product. Participants will attend for 25 visits primarily at their local recruiting hospital. For participants from the UK, some of the imaging will be performed at Invicro (London), and the surgery (including some visits before and after) and some imaging will be performed in Lund. All participants will be followed up for 36 months following surgery

Inclusion Criteria:Have given written informed consent to participate in the trialDiagnosed with PD as defined using Queens Square Brain Bank criteriaModerate disease as defined by having Hoehn and Yahr stage ≤ 3 in OFF stateDisease duration > 5 yearsMale or female, aged between 50 and 75 years (inclusive)Have a significant response to dopamine therapies as judged by the PI or other delegated clinicianAbility to travel to Lund for surgeryFollowed up for at least 12 months prior to inclusion in this trial in the TransEUro observational studyBe fluent in English/Swedish to enable completion of questionnaires as assessed by the PI or other delegated clinician at Cambridge/Lund, respectivelyHave received the full vaccination dose for COVID-19 as per local guidance, at least 3 weeks prior to consentBe approved by the TMG clinical sub-group for trial participationExclusion Criteria:Tremor dominant disease, as assessed by the PI or other delegated clinicianSignificant drug induced dyskinesias as defined by a score of > 2 in the Abnormal Involuntary Movement Scale (AIMS) dyskinesias rating scale, in any body part in the ON stateOngoing major medical or psychiatric disorders, including depression (MADRS > 20) and psychosis, that make participation unsuitable, as judged by the PI or other delegated clinicianAny contraindication to neurosurgeryUnable to be imaged using MRIExtensive ventral striatal loss or normal findings on F-DOPA PET at screeningSignificant cognitive impairment indicative of an incipient dementia/established dementia or values consistent with MoCA score of ≤ 24Unable to perform normal copying of interlocking pentagons and/or a semantic fluency score for naming animals of less than 20 over 90 secondsOther concomitant treatment with neuroleptics (including atypical neuroleptics) and/or cholinesterase inhibitorsPrevious neurosurgery to the brain, or cell or organ transplantation, or recipient of repeated blood transfusionsAny contraindication to immunosuppressive therapy, prophylactic antibiotics, and/or osteoporosis prophylaxis (refer to STEM-PD Trial Immunosuppressant Manual)High levels of pre-formed specific anti-HLA antibodies to the cell productTPMT deficiency < 10 pmol/h/mg HbHistory of documented severe/significant allergy requiring treatmentFemale who is pregnant or breastfeedingReceived an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks of the screening visit, or is currently enrolled in an interventional investigational trialFemale of childbearing potential or male unwilling to follow contraception requirements (see protocol section 12.15)Any other condition which, in the opinion of the investigator, makes the patient inappropriate for entry into the trial