Stem Cell Spinal Cord Injury Exoskeleton and Virtual Reality Treatment Study

The Stem Cell Spinal Cord Injury Exoskeleton and Virtual Reality (SciExVR) study is based on
the progress that researchers have made treating spinal cord injury (SCI) with bone marrow
derived stem cells (BMSC). While major improvements have remained elusive with other
approaches, modest benefits have been achieved.

The use of subarachnoid BMSC provided via intrathecal injection has resulted in improvements
for certain sensory and bladder functions. Exoskeleton treatment has shown certain benefits
in sensory, bowel and bladder function.

Intravenous (IV) BMSC have benefited stroke and other central nervous system damage. In the
sponsor's concomitant Neurologic Stem Cell Treatment (NEST) study for general neurologic
disease, benefit has been shown by combining IV with intranasal BMSC.

The SciExVR study uses paraspinal injections- meaning the BMSC are placed adjacent to the
spinal nerves which enter the spinal canal through the intervertebral foramen of the
vertebral bodies. The BMSC will be placed at the level of the injury on both sides of the
spine as well as approximately two segments above and two segments below. The investigators
believe this will allow entry into the spinal tissue at the injury site as well as to the
injured upper motor neuron pathways; lower motor neurons which may be injured; sensory
pathways; dorsal root ganglia at and below the site and autonomic ganglia. Placement in the
paraspinal tissue may extend the time that BMSC have to proliferate at, above and below the
vicinity of the spinal cord injury and interact with damaged cells in the spinal cord, spinal
roots, spinal nerves and paravertebral ganglion. Potential benefits of these interactions
include BMSC mitochondrial transfer to target cells, secretion of mRNA increasing target cell
activity, secretion of nerve growth factor and other neurotrophic factors beneficial to nerve
regrowth. Increased proliferation and contact time may increase neuronal transdifferentiation
of BMSC to neurons and/or neuroglia. Following paraspinal injections the patient receives the
remaining BMSC intravenously (IV) and also topically intranasally. BMSC given IV may enter
the central nervous system through the paraventricular organs in the brain to potentially
reach the ascending and descending pathways, thalamus, sensory cortex, motor cortex and
circulate through the cerebral spinal fluid (CSF). Intranasal provides access through the
axons of the Trigeminal (V) cranial nerves and entry into the brain at the level of the pons
with similar opportunity to move through the tissues.

BMSC are separated from bone marrow obtained from the posterior iliac crest with a single
aspiration on each side. The procedure is performed under general or MAC anesthesia at the
fully licensed surgical center so there is no discomfort in performing the procedure. The
BMSC are separated from the aspirate using an FDA cleared class II device.

After BMSC treatment patients who are in Arm 1 simply follow up with their own neurologists
at 1,3,6 and 12 months.

Those in Arm 2 require similar follow up and pursue treatment at centers that can provide
exoskeletal stimulation or physical therapy equivalent. Exoskeleton devices move the limbs of
the patient to provide stimulation to the muscles in a self directed fashion but similar to
physical therapy that is often performed for SCI. The investigators believe that Arm 2 may
provide stimulation of the upper and lower motor neurons and sensory receptors such as
exteroceptors and proprioceptors which may, in the presence of BMSC, assist in regeneration
or reactivation of the spinal cord pathways.

Patients in Arm 3 require similar follow up and may use Virtual Reality headsets or
equivalent to increase visualization of movement of the lower extremities and/or sensory
feedback. This may also help stimulate the upper and lower motor neurons and sensory
receptors.

Inclusion Criteria:

- Have documented functional damage to the spinal cord unlikely to improve with present
standard of care.

- If under current medical therapy (pharmacologic or surgical treatment) for the
condition be considered stable on that treatment and unlikely to have reversal of the
associated spinal cord damage as a result of the ongoing pharmacologic or surgical
treatment.

- In the estimation of Dr. Weiss and Dr. Silberfarb have the potential for improvement
with BMSC treatment and be at minimal risk of any potential harm from the procedure.

- Be over the age of 18 and capable of providing informed consent.

- Be medically stable and able to be medically cleared by their primary care physician
or a licensed primary care practitioner for the procedure. Medical clearance means
that in the estimation of the primary care practitioner, the patient can reasonably be
expected to undergo the procedure without significant medical risk to health.

Exclusion Criteria:

- All patients must be capable of an adequate neurologic examination and evaluation to
document the pathology. This will include the ability to cooperate with the exam.

- Patients must be capable and willing to undergo follow up neurologic exams as outlined
in the protocol.

- Patients must be capable of providing informed consent.

- In the estimation of Dr. Weiss and Dr. Silberfarb the BMSC collection and treatment
will not present a significant risk of harm to the patient's general health or to
their neurologic function. .

- Patients who are not medically stable or who may be at significant risk to their
health undergoing the procedure will not be eligible.

- Women of childbearing age must not be pregnant at the time of treatment and should
refrain from becoming pregnant for 3 months post treatment.