The purpose of this study is to determine whether mesenchymal stem cells (MSCs) can be
safely delivered to the cerebrospinal fluid (CSF) of patients with multiple system atrophy
(MSA). Funding Source - FDA OOPD.
The primary aim is to evaluate the safety and tolerability of intrathecal injection of
autologous MSCs in a dose escalation study in patients with MSA. Safety secondary goals
include to monitor changes in peripheral blood and in components of CSF, and monitor for any
changes of nervous system structures using MRI. Efficacy secondary goals include evaluating
potential efficacy by providing a number of studies and instruments that will detect changes
in the course of the disease in terms of autonomic and neurologic symptoms and deficits.
1. Participants aged 30-80 years old with a diagnosis of MSA based on clinical criteria
and standardized autonomic testing. This approach allows for identification of
patients with MSA with very high specificity and is yet sensitive enough to allow for
enrollment of patients at a disease stage at which an intervention on the natural
disease course has a meaningful impact on patient outcome. Patients therefore have to
fulfill Gilman Criteria (2000) for probable MSA of the parkinsonian subtype (MSA-P)
or cerebellar subtype (MSA-C) and have findings on autonomic function testing
suggestive of MSA (CASS ≥5 or a TST% ≥25%).
2. Participants who are less than 4 years from the time of documented MSA diagnosis.
3. Participants with an anticipated survival of at least 3 years in the opinion of the
4. Participants who are willing and able to give informed consent.
5. "Normal" cognition as assessed by Mini-Mental State Examination (MMSE). We will
require a value >24.
Any of the following conditions will exclude the participant from entering the study:
1. Women of childbearing potential who do not practice an acceptable method of birth
control. Acceptable methods of birth control in this study are: surgical
sterilization, intrauterine devices, partner's vasectomy, a double-protection method
(condom or diaphragm with spermicide), hormonal contraceptive drug (i.e., oral
contraceptive, contraceptive patch, long-acting injectable contraceptive) with a
required second mode of contraception.
2. Participants with a clinically significant or unstable medical or surgical condition
that, in the opinion of the investigator, might preclude safe completion of the study
or might affect the results of the study. These include conditions causing
significant central nervous system (CNS) or autonomic dysfunction, including
congestive heart failure, recent (<6 months) myocardial infarct, cardiopulmonary
disease, severe, uncontrolled hypertension, thrombocytopenia (<50 x 10(9)/L), severe
anemia (<8g/dl), immunocompromised state, liver or kidney disease (creatinine
>2.3mg/dl), uncontrolled diabetes mellitus (HbA1c >10g%), alcoholism, amyloidosis,
uncontrolled hypothyroidism, sympathectomy, unstable peripheral neuropathies,
concurrent infections, orthopedic problems that compromise mobility and activity of
daily living, cerebrovascular accidents, neurotoxin or neuroactive drug exposure,
parkinsonism due to drugs (including neuroleptics, alpha-methyldopa, reserpine,
3. Participants with malignant neoplasms.
4. Participants who have taken any investigational products within 60 days prior to
5. Medications that could affect autonomic function. If patients are taking those
medications, those will be suspended prior to autonomic testing. Therapy with
midodrine, anticholinergic, alpha and beta adrenergic antagonists or other
medications that affect autonomic function will be withdrawn 48 hours prior to
autonomic evaluations. Fludrocortisone doses up to 0.2 mg per day will be permitted.
6. Diseases with features of Parkinsons Disease; e.g., diffuse Lewy body disease,
progressive supranuclear palsy, essential tremor, hereditary olivopontocerebellar
atrophy, or postencephalitic parkinsonism.
7. Dementia (DSM-IV criteria - American Psychiatric Association 1994). The score on the
Mini-Mental State Examination must be >24.
8. History of electroconvulsive therapy.
9. History of brain surgery for Parkinsons disease.
10. Patients with contraindication for MRI scanning, including those with
11. Patients with active systemic infection or local infection, which is close to the
spinal injection site