Safety of Autologous Human Schwann Cells (ahSC) in Subjects With Subacute SCI

Schwann cells are excellent candidates for transplantation into humans with SCI. Large
numbers of ahSC can be derived for autologous implantation after a minor surgery for
peripheral nerve harvesting, and purification and expansion of the cells in culture.
Autologous cells offer important safety advantages that include no need for immune
suppression, minimal risk of disease transfer, and a low risk of tumorigenicity.

Since 1990, scientists at the Miami Project to Cure Paralysis have generated extensive
preclinical data suggesting Schwann cell transplantations are successful in rodents with SCI.
The most recent work has focused on contusive injury models that are relevant to human
injury. They have also been largely responsible for developing an efficient method for
procuring large, essentially pure populations of human Schwann cells from adult peripheral
nerve.

The rationale for implantation of ahSC in people with acute SCI is based on the evidence that
Schwann cells are neuroprotective and are capable of myelinating axons. Using mitogen
expanded human Schwann cells in SCID mice and athymic female nude rats demonstrated that
human Schwann cells can survive and are capable of enhancing axonal regeneration and forming
myelin after transplantation in animals with sciatic nerve transection or thoracic spinal
cord transection. The proposed clinical trial will advance knowledge about the safety and
feasibility of a cell-based treatment strategy for human SCI.

This Phase 1 clinical trial will employ an open label, unblinded, nonrandomized and
non-placebo controlled dose-escalation design to evaluate the safety of transplantation of
ahSC transplantation in subjects with subacute SCI.

A sural nerve harvest will occur within 30 days post-injury. Standard-of-care medical
treatment and rehabilitation will proceed while the cells are being processed in a cGMP
facility. No later than 72 days post-injury, the ahSC product will be administered via a
single injection into the cavity of the spinal cord lesion.

Safety and efficacy assessments will be performed at week 1 and 2 post-transplantation and 2,
6, and 12 months post-transplantation.

Inclusion Criteria:

- 1) Persons with traumatic SCI that occurred within the previous 30 days.

- 2) Between the ages of 18 and 60 at last birthday.

- 3) SCI at a thoracic level between T3-T11 as defined by MRI and the most caudal level
of intact motor and sensory function on the International Standards for Neurological
Classification of Spinal Cord Injury (ISNCSCI).

- 4) Acute SCI with ISNCSCI grade A impairment at time of enrollment.

Exclusion Criteria:

- 1) Persons with penetrating injury of the spinal cord or complete transection of the
cord, including bone fragment lacerations, as identified by magnetic resonance imaging
(MRI).

- 2) Persons with a lesion in the conus medullaris, cauda equina, or lower extremity
peripheral nerve.

- 3) Persons unable to safely undergo an MRI.

- 4) Persons in whom adequate MRI imaging cannot be obtained.

- 5) Persons who have developed a pulmonary embolism (PE) or deep vein thrombosis (DVT).

- 6) Other traumatic injuries (e.g., CHI, another level of SCI) affecting the ability to
provide informed consent and participate fully in rehabilitation.

- 7) Persons with self-reported persistent severe neuropathic pain, inadequately
controlled by non-narcotic medication.

- 8) Persons with severe persistent mechanical or thermal hypersensitivity/allodynia at
the neurological level or rostral to it as documented by clinical testing.

- 9) Pregnant women or a positive pregnancy test in those women with reproductive
potential prior to enrollment.

- 10) Presence of systemic disease that might interfere with subject safety, compliance,
or evaluation of the condition under study.

- 11) Presence of any unstable medical or psychiatric condition that could reasonably be
expected to subject the participant to unwarranted risk from participation in the
study or result in a significant deterioration of his/her clinical course.

- 12) Body Mass Index (BMI) > 35.

- 13) History of active substance abuse.

- 14) Persons who have participated in other experimental treatments within the past 90
days deemed by the PI to represent a possible confound or enrolled in any other
ongoing trial.

- 15) Persons with significant lower extremity injury, previous surgery, or amputation
such that would preclude satisfactory sural nerve harvest.

- 16) Persons allergic to gentamicin

- 17) Persons who test positive for HIV or Hepatitis B or C virus.

- 18) Baseline entry criteria for renal function, CBC, INR, and liver tests including
serum albumin, total bilirubin, alanine transaminase (ALT), aspartate transaminase
(AST), alkaline phosphastase (ALP), and gamma glutamyl transpeptidase (GGT). Persons
with lab values that are concerning in the context of SCI may be excluded from
participating in the trial if these indicate chronic or severe acute pathology.

- 19) Persons with autoimmune diseases, for which chronic corticosteroids or
immunosuppression therapy may be needed.

- 20) Persons with clinically documented malignancy in the past 5 years except for
treated non-melanoma skin cancers.