A double-blind, randomized, placebo-controlled, Multiple Ascending Dose (MAD) study in healthy elderly volunteers and Alzheimer's Disease (AD) and Parkinson's disease (PaD) patients to investigate the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) effects of multiple intravenous infusions of NX210c

Participants are eligible to be included in the study only if all of the
following criteria apply:
Part A:
1. Signed informed consent prior to any study-mandated procedure.
2. Healthy adult male or female participants, as determined by the
Investigator, based upon a medical evaluation including medical history,
physical examination, neurological examination, MMSE, MRI, lab tests and ECG.
3. Aged >= 55 years, inclusive at screening, and with a maximum weight of 110 kg.
4. Body mass index (BMI) between 18 and 32 kg/m2, inclusive at screening.
5. MMSE score of >= 25 at screening.
6. Able to communicate well with the Investigator and staff in the Dutch
language and willing to comply with the study restrictions.
7. For female participants: only women of non-childbearing potential (WONCBP)
can participate in this study. WONCBP have either undergone surgical
sterilization (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy; participant reported information) at least 90 days prior to
baseline or are postmenopausal (amenorrheic for > 12 consecutive months before
screening, confirmed by FSH levels > 26 IU/L). Essure® fallopian tube coil
placement is not accepted as surgical sterilization because of the high failure
rate.
8. For male participants: When engaging in sexual intercourse with WOCBP, the
male participant must use a male barrier method such as a latex or polyurethane
condom from the start of dosing throughout the clinical study period, and for
90 days after the final administration of study intervention.
9. For male participants: The participant must not donate sperm at any time
from the start of dosing, throughout the clinical study period, and for 90 days
after the final administration of study intervention.

Part B (AD and PaD patients):
All patients:
1. Signed informed consent prior to any study-mandated procedure.
2. Aged >=55 years old, inclusive at screening, and with a maximum weight of 110
kg.
3. Body mass index (BMI) between 18 and 32 kg/m2, inclusive at screening.
4. Able to communicate well with the Investigator and staff in the Dutch
language and willing to comply with the study restrictions.
5. Ability to walk, at least with an assistive device.
6. Living independently and not in an institution. Home care is allowed.
7. Have stable permitted medications for 4 weeks prior to dosing.
8. For female participants: only women of non-childbearing potential (WONCBP)
can participate in this study. WONCBP have either undergone surgical
sterilization (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy; participant reported information) at least 90 days prior to
baseline or are postmenopausal (amenorrheic for > 12 consecutive months before
screening, confirmed by FSH levels > 26 IU/L). Essure® fallopian tube coil
placement is not accepted as surgical sterilization because of the high failure
rate.
9. For male participants: When engaging in sexual intercourse with WOCBP, the
male participant must use a male barrier method such as a latex or polyurethane
condom from the start of dosing throughout the clinical study period, and for
90 days after the final administration of study intervention.
10. For male participants: The participant must not donate sperm at any time
from the start of dosing, throughout the clinical study period, and for 90 days
after the final administration of study intervention.

AD patients only:
11. Meet diagnostic criteria for Alzheimer's Disease according to the National
Institute on Aging (NIA) and the Alzheimer's Association published guidelines
(NIA-AA) 2018, confirmed by cerebrospinal fluid analysis.
12. A brain MRI prior to study inclusion consistent with the clinical diagnosis
of AD and without findings of significant exclusionary abnormalities.
13. A MMSE score van >= 20

PaD patients only:
11. A diagnosis of PaD, confirmed by a neurologist.
12. Hoehn & Yahr Stage <= III at Screening.
13. A brain MRI prior to study inclusion consistent with the clinical diagnosis
of PaD and without findings of significant exclusionary abnormalities.

Participants who meet any of the following criteria will be excluded from study
entry:
Part A:
1. Evidence of any history, or any active or chronic disease or condition that
could interfere with, or for which the treatment of might interfere with, the
conduct of the study, or that would pose an unacceptable risk to the subject in
the opinion of the investigator (following a detailed medical history, physical
examination, vital signs (systolic and diastolic blood pressure, pulse irate,
body temperature and 12-lead electrocardiogram (ECG)). Minor deviations from
the normal ranges may be accepted, if judged by the Investigator to have no
clinical relevance.
2. History of any known neurologic disease, cognitive impairment, or diagnosed
decline in cognitive function abnormal related to the age, or history of
seizure, (significant) head trauma, loss of consciousness, or significant
neuroimaging findings, including but not limited to any previously known or
discovered abnormalities on screening brain MRI that evoke other neurological
diagnosis indicative of clinically significant abnormality.
3. Currently active known psychiatric disease or usage of anti-psychotic
medications, anti-depressants drugs, addiction to drugs or alcohol, positive
answer at screening to item 4 or 5 on the Colombia-Suicide Severity Rating
Scale (C-SSRS) or suicidality which could pose a risk to study participation or
determination of the endpoints, as judged by the investigator
4. Presence of a clinically significant infection in the judgment of the
Investigator, within 7 days of baseline.
7. Any clinically significant abnormalities in laboratories (e.g. aspartate
aminotransferase (AST) >2 × upper limit of normal (ULN); alanine
aminotransferase (ALT) >2 × ULN; total bilirubin >2 × ULN; serum creatinine
>2.0 × ULN, coagulation disorders including platelet count <100 × 103/µl) at
screening or baseline. Measurements may be repeated at the investigator*s
discretion.
8. Glomerular filtration rate (GFR) of <60 mL/min as estimated with the Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening or
baseline. Measurements may be repeated at the investigator*s discretion.
11. Abnormal findings in the resting ECG at screening or baseline (measurements
may be repeated at the investigator*s discretion)

Part B (AD and PaD patients):
All patients
1. Clinically significant abnormalities, as judged by the investigator, in test
results (including blood chemistry, hematology, virology, urine, medical
history, physical examination, vital signs (systolic and diastolic blood
pressure, pulse rate, body temperature and 12-lead electrocardiogram (ECG)).
Minor deviations from the normal ranges may be accepted, if judged by the
Investigator to have no clinical relevance. In the case of uncertain or
questionable results, tests performed during screening may be repeated before
randomization to confirm eligibility or judged to be clinically irrelevant.
2. Currently active known psychiatric disease or usage of anti-psychotic
medications, anti-depressants drugs, addiction to drugs or alcohol, positive
answer to item 4 or 5 on the Colombia-Suicide Severity Rating Scale (C-SSRS) or
suicidality which could pose a risk to study participation or determination of
the endpoints, as judged by the investigator.
3. Presence of a clinically significant infection in the judgment of the
Investigator, within 7 days of baseline.
4. Any clinically significant abnormalities in screening laboratories (e.g.,
aspartate aminotransferase (AST) >2 × upper limit of normal (ULN); alanine
aminotransferase (ALT) >2 × ULN; total bilirubin >2 × ULN; serum creatinine
>2.0 × ULN).
5. Systolic blood pressure (SBP) greater than 150 or less than 90 mm Hg, and
diastolic blood pressure (DBP) greater than 95 or less than 50 mm Hg at
screening or baseline. Measurements may be repeated at the investigator*s
discretion.
6. Use of prohibited medications (e.g., anti-epileptic drugs).
7. Administration of a vaccine in general within 2 weeks before study drug
administration, and 4 weeks anti-COVID vaccines with mRNA in particular.
8. Loss or donation of blood over 500 mL within 90 days (males) or 120 days
(females) prior to screening or intention to donate blood or blood products
during the study.
9. Unsatisfactory venous access.
10. Participation in an investigational drug or device study (last dosing of
previous study was within 90 days prior to first dosing of this study)
including not having previously been dosed with NX210c.
11. History of abuse of addictive substances (alcohol, illegal substances) in
the past 5 years of screening or current use of more than 21 units alcohol per
week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or
any other addictive agent.
12. Positive test for alcohol and/or drugs of abuse at screening or baseline
(urine drug screen or alcohol breath test). Measurements may be repeated at the
investigator*s discretion.
13. Smoker of more than 10 cigarettes per day prior to screening or who use
tobacco products equivalent to more than 10 cigarettes per day and unable to
abstain from smoking whilst in the unit. Former smokers of more than 10
cigarettes per day will be eligible, provided they have not smoked more than 10
cigarettes per day for at least 3 months prior to the dosing of study drug.
14. Any contra-indication to glucose 5% or allergy to any component of the
formulation, including corn allergy.
15. For CSF sampling, any of the criteria below:
a. History of clinically significant hypersensitivity to local anesthetics that
may be used for LP (e.g., lidocaine).
b. Criteria that would preclude an LP, such as a local infection at the site of
the LP, <100 × 103/µl platelet count at screening or clinically significant
coagulation abnormality or significant active bleeding, or treatment with an
anticoagulant or treatment with more than two antiplatelet agents.
c. History of clinically significant back pathology and/or back injury (e.g.,
degenerative disease, spinal deformity, or spinal surgery) that may predispose
to complications or technical difficulty with LP.
16. Any contraindication to MRI and DCE-MRI scanning, such as implanted metal
clips or wires of the type that may concentrate radiofrequency fields or cause
tissue damage from twisting in a magnetic field (e.g., aneurysm clips),
implanted neural stimulators, implanted cardiac pacemakers or auto
defibrillators, cochlear implants, ocular foreign bodies (e.g., metal
shavings), any implanted device (pumps, infusion devices, etc.), or shrapnel
injuries. Any contraindication of gadolinium for DCE-MRI. Inability to undergo
MRI according to the investigator*s opinion (e.g., unable to lay still for the
duration of the MRI).
17. Positive screening cultures for Multidrug resistant bacteria (BRMO) and/or
Methicillin resistant staphylococcus aureus (MRSA) or no consent to perform
BRMO and MRSA culture in case of increased risk for colonization with these
bacteria.

AD patients only:
18. Dementia due to any condition other than AD, including VaD.
19. Clinically significant neurological disease other than AD, including but
not limited to epilepsy or anti-epileptic drug therapy, stroke within 6 months
before screening, or concomitant with onset of dementia, significant
neuroimaging abnormalities, previously known or discovered on screening brain
MRI, concussion or other acute head trauma in the past six months.
20. Use of memantine within 21 days before first dose.

PaD patients only:
18. Other known or suspected cause of Parkinsonism other than idiopathic PaD,
including but not limited to, progressive supranuclear gaze palsy, drug- or
toxin-induced parkinsonism, essential tremor, primary dystonia, vascular
parkinsonism.
19. Clinically significant neurological disease other than PaD, such as
multi-infarct dementia, Huntington's disease, normal-pre