Bone Marrow collection in Healthy volunteers

Stem cells are able to modify neuro-inflammation induced by a traumatic event
of the central nervous system (traumatic spinal cord injury and/or traumatic
brain injury) or by neurodegenerative processes accompanying diseases such as
for example Amyotrophic Lateral Scleroses (ALS). Without intervention these
diseases cause collateral damage of neural tissue , which can be decreased by
the paracrine and immune modulating capabilities of stem cells. Intervention
with stem cells in an acute spinal cord injury can decrease the secondary
inflammatory cascades and can Improve locomotor functioning and can improve the
autonomic functioning of the Central Nervous System needed for better
breathing, bowel and bladder control.
In case of ALS stem cells can slow down the disease progression resulting in a
better quality of life and an increased life expectancy of the patient.
Preclinical evidence is present and confirmed that this can be achieved by stem
cells. However, efficacy has to be confirmed in a randomised and placebo
controlled clinical trial with patients. At the moment Neuroplast BV has
completed its complete preclinical program, proof and concept studies and
regulatory preclinical safety inclusive.

Neuroplast has scheduled to start in 2018 with a phase I and a phase II/III
clinical trial with patients with a traumatic spinal cord injury to confirm the
efficacy and safety in humans. A GMP license to produce clinical grade
Neuro-Cells is mandatory for these scheduled studies. To maintain the GMP
status during the year, Neuroplast has to perform sterility testings,
validation tests including in-proces controlling and comprehensive
characterisation and shelf life testing of the end product Neuro-Cells. With
the gathered information Neuroplast is able to compile an IMPD and IB regarding
its product Neuro-Cells. Especially for the phase II/III multicenter study,
shelf life and transport conditions for respectively bone marrow and
respectively Neuro-Cells has to be defined and confirmed. The phase II study is
ongoing with the centers located in Copenhagen, and Toledo. The phase I study
was executed in Toledo Spain and safety was established successfully. Several
tests needs to be validated before the Phase III is allowed to start.

This study is written to collect bone marrow from healthy volunteers needed to
produce Neuro-Cells. The produced Neuro-Cells are only used for vitro and vivo
testing, for sterility testing and comparison, for characterisation and shelf
life testing and for validation and in proces controlesof the manufacturing.
None of these products will be used to give back to patients. Characterisation
shall be performed by Flowcytometry and the sterility determine with the use of
rapid tests shall be compared with the use of PCR multitest to detect foreign
bacteria DNA. Shelf life and optimal storage conditions testing are needed
regarding the safe transportation to the European centers Copenhagen and
Toledo.

The total time burden is estimated at 120 minutes. The risk accompanying blood
sampling and bone marrow collection is very low. Bone marrow collection is a
routine and standardised medical procedure. Experience during the years 2016 to
2022 with 58 volunteers (iCELL1 and iCELL2) confirmed the safety of the
procedure. No volunteer needed extra medical attention. All the volunteers were
able to perform all there daily activities without hinder and complaints.
The risk of determining the serology status is that a volunteer may get a
positive result which could have consequences for the individual volunteer. In
this study the medical investigator is able to act and shall take care to help
in coaching and informing the GP.