A Phase I Study in Healthy Volunteers and Parkinson's Disease (PD) Patients.

PART 5 - Currently recruiting in Parkinson's Disease Patients Inclusion Criteria 1. Male and female participants aged ≥ 40 to ≤ 75 years. 2. Male or female participants. Female participants of childbearing potential must be willing to use highly effective forms of contraception (refer to Section 9.7.1 for details on highly effective methods of contraception and definitions of women of childbearing potential and of fertile men): 3. Body mass index (BMI) between 18 and 34.0 kg/m2, inclusive. 4. If being treated with selective serotonin reuptake inhibitors (SSRIs) for anxiety/ depression, must be on a stable dose for 60 days prior to Day -1 and must remain on that dose for the remainder of the study. 5. Must have had other causes of Parkinsonism excluded 6. No clinically significant history of previous allergy/ sensitivity to MTX325 or any of the excipients contained within the IMP. 7. Participant with a negative urinary drugs of abuse (DOA) screen (excluding alcohol). 8. Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen \[HbsAg\]) and hepatitis C virus antibody (HCV Ab) test results at Screening. 9. No history of torsade de pointes or long QT syndrome and no heart failure, hypokalaemia, or any other additional cardiac risk factors if judged clinically significant in the opinion of the Investigator. 10. No clinically significant abnormalities in vital signs during the screening period. 11. Able to perform all protocol assessments and comply with the study visit schedule. 12. Able and willing to provide informed consent. 13. Clinically established PD as per MDS Criteria\[ 14. Absence of dementia as shown by a baseline Montreal Cognitive Assessment (MoCA®) Exclusion Criteria 1. A clinically significant history of gastrointestinal disorders or any significant medical conditions that would be likely to influence IMP absorption, or evidence of clinically significant central nervous system, respiratory, cardiovascular or metabolic dysfunction or other significant medical conditions with potential to impact participant safety or hinder interpretation of study results. 2. Clinically significant neurologic disorder other than PD, including history of stroke within 12 months of Screening, seizure within 5 years of Screening, or head trauma with loss of consciousness within 6 months of Screening. 3. Those with known PD risk genes (per medical history). 4. Reside in a nursing home or assisted care facility. 5. No more than 2 PD related freezing episodes or falls in the past 6 months. 6. Any condition that may predispose participant to complications or technical difficulty with lumbar puncture, in the opinion of the Investigator. 7. Participants who have conditions that would preclude a lumbar puncture (LP), such as a local infection at the site 8. Participant who has a history of clinically significant hypersensitivity to local anaesthesia, or its derivatives used during CSF collection or to any medication used to prepare the area of LP. 9. Reports having experienced suicidal ideation (Type 4 on 5 on the Columbia-Suicide Severity Rating Scale \[C-SSRS©\] 10. Participants should not be in receipt of any known MATE2k substrates 11. Plan to receive or administration of rotigotine, catechol-o-methyltransferase (COMT) inhibitors (e.g., entacapone, tolcapone or opicapone), neuroleptics, venlafaxine, NMN, nicotinamide riboside or non-selective Monoamine oxidase \[MAO\] inhibitors within 7 days or 5 half-lives (whichever is longer) prior to first dose and during the study conduct. 12. Clinically significant abnormal test results for serum biochemistry, haematology, coagulation and/or urine analyses as determined within 45 days before first dose of IMP. 13. A clinically significant history of gastrointestinal disorder likely to influence IMP absorption. 14. Participant has any condition that, in the opinion of the investigator, is clinically significant and may put the participant at greater safety risk, influence response to study product, or interfere with study assessment. 15. Inability to communicate well with the Investigators. 16. Participation (dosed) in a NCE clinical study within the previous 3 months or five half lives 17. Donation of 450 mL or more blood within the 3 months before the first dose of IMP. 18. Female participants who are pregnant, breastfeeding or lactating. 19. Clinically significant abnormalities in 12-lead electrocardiogram (ECG) 20. Participants with recent COVID-19 infection without resolution of symptoms 21. Participants who have received a COVID-19 vaccine injection from the Screening visit up to first dose of IMP 22. A clinically significant history of drug or alcohol abuse within the past 2 years. 23. Currently prescribed treatment for Parkinson's Disease symptoms. 24. Any history of allergy/atopy including drug-induced allergy history of severe cutaneous adverse reaction or other type 4/delayed-type hypersensitivity. 25. Current or previous history of eosinophilia with either unknown cause, or where known, the inciting factor is not removed or avoided. 26. Previous history of Erythema Multiforme and/or identified current risk factor(s) for Erythema Multiforme 27. Participant has any contra-indication to PET or MRI as determined by screening procedures and PET and MRI safety questionnaires as conducted by the site. 28. Clinically significant history of previous allergy/ sensitivity to \[18F\] FDG. 29. Participants who have had previous exposure to ionizing radiation 30. Chronic kidney disease defined as glomerular filtration rate (GFR) 1.5 × the upper limit of normal (ULN) or ALT or AST \>3 × ULN or if participant has Child-Pugh Class C cirrhosis or equivalent severe hepatic impairment. 31. Hepatic disease or altered liver function as defined by total bilirubin \>1.5 × the upper limit of normal (ULN) or ALT or AST \>3 × ULN or if participant has Child-Pugh Class C cirrhosis or equivalent severe hepatic impairment. 32. Patients with un