Synaptic Loss in Multiple System Atrophy

Exclusion Criteria

• •MSA group:
• •History of other neurological disorders or intracranial co-morbidities, such as stroke, haemorrhage, space-occupying lesions.
• •Presence of supranuclear gaze palsy. Presence of any clinically significant medical condition (including cardiovascular, respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or other disease) that, based on the judgement of the investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject's ability to complete the study, or could influence the study results.
• •Severe-to-complete dependence on caregivers (score \>3 on UMSARS Part IV, Global Disability), severe impairment of swallowing (score ≥3 on UMSARS Part I, Question 2), or frequent falls (score ≥3 on UMSARS Part I, Question 8) at Screening.
• •Presence of any of the following MRI contraindications: pacemaker; cardiac defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted medical device (e.g. Swan-Ganz catheter, insulin pump); or metal fragments or foreign objects in the eyes, skin, or body. If the principal investigator considers the presence of any of the above not to be a contraindication to MRI in a given subject, the investigator may obtain approval from the MR operators based on a discussion of the case.Negative modified Allen test in both hands.
• •History of claustrophobia or back pain that makes prolonged laying on the MRI or PET scanner intolerable.
• •Pregnancy, lactation, or, if female of childbearing potential, positive urine β-hCG at screening or prior to PET scan.
• •Use of drugs acting on SV2A such as antiepileptics (e.g. levetiracetam or brivaracetam).
• •History of brain surgery for parkinsonism or stem cell treatment. Clinically significant blood clotting or bleeding disorder, including clinically significant abnormal findings in laboratory assessments of coagulation or hematology.
• •Current or recent history of alcohol or drug abuse / dependence (except nicotine dependence).
• •History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin.
• •Hemoglobin A1c (HbA1c) ≥ 6.5% at screening. Uncontrolled/poorly controlled diabetes mellitus.
• •For subjects participating in optional CSF sampling:
• •Any spinal malformation or other aspects (e.g. tattoos) / clinical findings (e.g. papilledema) that may complicate or contraindicate lumbar puncture, as judged by the investigator.
• •Neoplasm or other space-occupying intracranial lesion on MRI. Any clinically important abnormality, as determined by the investigator, on physical examination or vital signs, ECG, or clinical laboratory test results other than abnormality due to a stable, well-controlled medical condition; or any abnormality that could be detrimental to the subject or could compromise the study.
• •PSP group:
• •History of other neurological disorders or intracranial co-morbidities, such as stroke, haemorrhage, space-occupying lesions.
• •Inclusion in any clinical trial with investigational drugs targeting tau. Presence of any clinically significant medical condition (including cardiovascular, respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or other disease) that, based on the judgement of the investigator, is clinically unstable, is likely to deteriorate during the course of the study, could put the patient at risk because of participation in the study, could affect the subject's ability to complete the study, or could influence the study results.
• •Presence of any of the following MRI contraindications: pacemaker; cardiac defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted medical device (e.g. Swan-Ganz catheter, insulin pump); or metal fragments or foreign objects in the eyes, skin, or body. If the principal investigator considers the presence of any of the above not to be a contraindication to MRI in a given subject, the investigator may obtain approval from the MR operators based on a discussion of the case.
• •Abnormal modified Allen test in both hands. History of claustrophobia or back pain that makes prolonged laying on the MRI or PET scanner intolerable.
• •Pregnancy, lactation, or, if female of childbearing potential, positive urine β-hCG at screening or prior to PET scan.
• •History of brain surgery for parkinsonism or stem cell treatment. Clinically significant blood clotting or bleeding disorder, including clinically significant abnormal findings in laboratory assessments of coagulation or hematology.
• •Current or recent history of alcohol or drug abuse / dependence (except nicotine dependence).
• •History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin.
• •For subjects participating in optional CSF sampling:
• •Any spinal malformation or other aspects (e.g. tattoos) / clinical findings (e.g. papilledema) that may complicate or contraindicate lumbar puncture, as judged by the investigator.
• •Neoplasm or other space-occupying intracranial lesion on MRI. Any clinically important abnormality, as determined by the investigator, on physical examination or vital signs, ECG, or clinical laboratory test results other than abnormality due to a stable, well-controlled medical condition; or any abnormality that could be detrimental to the subject or could compromise the study.