Phase 1 Study of Autologous Mesenchymal Stem Cell in Multiple System Atrophy

Project: Research project

Project Details


PROJECT SUMMARY/ABSTRACT Multiple system atrophy (MSA) is a rare, sporadic multi-system progressive and
uniformly fatal disorder characterized by autonomic failure, orthostatic hypotension,
neurogenic bladder/erectile dysfunction, cerebellar ataxia, and parkinsonism. MSA is
characterized by glial cytoplasmic inclusions of abnormally aggregated ¿-synuclein, and
resulting neuronal loss in the striatum, cerebellum, brainstem, cortex, and spinal cord.
Although the precise mechanism by which ¿-synuclein aggregation leads to neuronal
loss is unproven, recent evidence suggests resulting deficiency of growth factors,
especially BDNF and GDNF.
Mesenchymal stem cells (MSCs) are multipotent stem cells and are capable of
differentiating into various cell types under appropriate conditions. Additionally, MSCs
secrete various cytotrophic factors that, in turn, exert neuroprotective effects. Animal
studies demonstrate that human MSCs have a protective effect against progressive
dopaminergic and striatal neuronal loss, and recently, the neuroprotective effects of
MSCs were confirmed in a transgenic mouse model of MSA. Furthermore, a positive
open-label study using intracarotid and intravertebral arterial MSC delivery to patients
with MSA was recently followed up with a double-blind placebo controlled trial in Korea,
reporting significantly slower disease progression in the MSC treated patient cohort.
Since to this point, there is no known intervention that can alter the disease course, and
symptomatic treatment options for MSA are less than satisfactory, these recently
reported Korean studies have been received with great interest, but unfortunately, safety
concerns regarding the intraarterial administration resulting in cerebral ischemic lesions
have dampened the excitement. We and others have recently developed platforms that
allow for safe MSC delivery directly into the spinal fluid; this intrathecal approach
overcomes the safety concerns associated with intraarterial administration, and
additionally should deliver stem cells into the CNS more effectively.
In response to the rare disease RFA, we now propose a safety study on intrathecal
adipose-derived autologous MSC treatment of MSA utilizing a dose-escalation protocol,
with a secondary goal of assessing the efficacy of this approach using carefully selected
and validated measures of neurologic and autonomic deficits. We hypothesize that this
approach is safe and tolerable, and that increasing doses of MSCs will result in graded
slowing of progression, stabilization, or improvement of neurologic and autonomic
deficits. The trial will use escalating doses of MSCs over three patient groups of 8
patients each (single dose of 1 x 107 cells, two doses of 5 x 107 cells each, and two
doses of 1 x 108 cells each). During stem cell administrations, patients will be
hospitalized for 3 days, then will be followed weekly for 4 weeks following the last MSC
administration (early follow-up), and then will be evaluated at 6 and 12 months (late-
follow-up) with standardized neurologic and autonomic instruments, and additional
phone follow-up at 3 and 9 months.
Patients will be recruited using strict inclusion and exclusion criteria that ensure patients
have well-established MSA, but are still at a disease stage that allows for detection of a
change in the disease stage (still evolving, not end-stage).
Effective start/end date9/10/148/31/17


  • National Institutes of Health: $200,000.00
  • National Institutes of Health: $200,000.00
  • National Institutes of Health: $200,000.00


  • Medicine(all)

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