Day 1 :
Keynote: The RegenerAge Combinatorial Bio-Interventions using Bioquantine® and allogeneic Mesenchymal Stem Cells combined with a spinal cord stimulation system in a No Option patient with ASIA-A classification
Time : 10:00-11:00
Joel Isaias Osorio Garcia is the CEO and Founder of Biotechnology and Regenerative Medicine at RegenerAge™. He is also the Vice President of International Clinical Development for Bioquark, Inc., Founder and President for the Dr. Jois A.C initiative Advance Fellow by the American Board of Anti-Aging and Regenerative Medicine. He is also the Visiting Scholar at University of North Carolina at Chapel Hill (Dermatology). Fellow in Stem Cell Medicine by the American Academy of Anti-Aging Medicine and University of South Florida.
In 1973 the American Spinal Injury Association made the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). In this clinical review our patient was classified after the vertebral fixation surgery with a ASIA-A scale injury after suffering a fracture and luxation at T-12-L1, having total spinal cord section. Based on the research made by Sergei Paylian, PhD on animal models and the safety use of allogeneic MSCs demonstrated on multiple animal models applications, we decided to apply a experimental translational medical protocol based the research and the previous outcomes obtained by Hamid and MacEwan and decided to customize it exclusively to our patient based on the clinical evidence and personalizing the therapy on evidence. The medical team designed an ambulatory method utilizing a C-arm to apply the allogeneic MSCs in situ and using a intrathecal (subdural) catheter using a slow pump release system for the rest of the biological material with an optimum tolerance and minor side effects (mild fever, miyalgias and headache) on the first 48 hrs hour after application. The experimental use of mRNA Bioquantine® was well tolerated with its purified form (intra and extra-oocyte liquid phases of electroporated oocytes) showing to be well tolerated by the patient without any anaphylactic reaction. The current clinical report is meant to demonstrate the beneficial changes with the use of Bioquantine® and its administration in a patient with a severe SCI offering a possible optional therapy and potential neuroregeneration in this clinical condition. Mesenchymal Stem Cells (MSCs) are ideal for cell-based therapy in various inflammatory diseases because of their immunosuppressive and tissue repair properties. Moreover, their immunosuppressive properties and low immunogenicity contribute to a reduced or weakened immune response elicited by the implantation of allogeneic MSCs compared with other cell types, allogeneic MSCs are a promising option because of their low immunogenicity and immunosuppressive and tissue repair capabilities. The positive findings throughout the evolution of our protocol for spinal cord injury with the obtained results at this stage is a promising scientific based and evidence based medicine protocol that can be offered in the near future as an option for severe SCI patients. The functionality of the RestoreSensor® SureScan® by providing the electric stimulation fortifies the medical outcome and has given the patient the confidence to perform his physical rehabilitation with more energy for a longer time by the increase or decrease of the intensity of it according to the type of exercise regulated by the control-battery he handles. At this date, after 8 intrathecal applications of allogeneic MSCs and Bioquantine® in situ combined together we have got the following outcomes: an improvement in sensitivity, strength in striated muscle and smooth muscle connection by increased muscle mass and sphincter control, at 23 months after the first regenerative therapy and 12 months after the placement of RestoreSensor® the patient is showing an evident improvement on his therapy of physical rehabilitation (legs movement and control of them) having the following movements reported by the physical therapist: a) hip: adduction and external rotation, extension, abduction, internal rotation; b) knee: flexion; c) toe: MP and IP extension, also reporting an easier and functional crawling forward and backwards and since 3 months ago the patient is capable to stand on his knees for 2 or more minutes without any support and taking small steps on his knees forward and backwards for the first time in his process, showing a progressively important functionality on both limbs, voluntary movement at both feet and an increase in sensory perception. As we are probing in the case, combinatorial biologics can be used safely with other electronic disposals and bring a major benefit to SCI patients. With this unique combination we can give an option to those no option patients and create many more to improve patients quality of life.
Kristine Freude is an Associate Professor at the University in Copenhagen and Director of the Center for Excellence in Neuroscience BrainStem. She has been at the University of California at Irvine, where she received her training in Stem Cell Biology funded by the California Institute for Regenerative Medicine (CIRM). Her current research is focused on disease modeling using induced Pluripotent Stem Cells (iPSC) from patients with neurodegenerative diseases such as Alzheimer's as well as CRISPR-Cas9 gene edited iPSCs carrying mutations associated with neurodegenerative diseases. Her research is funded by Innovation Foundation Denmark, Novo Nordisk Foundation and the Danish Alzheimer's Foundation.
Alzheimer’s Disease (AD) is the most common cause of dementia with currently no curative treatments available. To combat this disease it is crucial to understand the precise cellular disease pathology in order to define new targets for intervention. We have built a human induced pluripotent stem cell platform enabling us to study the disease mechanisms in the relevant target cells: human neurons, astrocytes and microglia. Our focus is on PSEN1, APP and sporadic forms of AD. For all of our lines with defined mutations we have generated CRISPR-Cas9 gene edited controls replacing the mutant nucleotide and generating isogenic controls. Our studies have so far revealed abnormal cristae formation in mitochondria accompanied by aberrant mitochondrial distribution and mitochondrial respiration deficiency. Other cellular phenotypes revealed abnormal ultrastructure’s of the Golgi Apparatus (GA), with shortened and dilated cisternae and increased surface area. The GA’s were scattered around the nuclei, indicating GA fragmentation. Furthermore reduced synaptic density and glutamine metabolic defects were part of the disease phenotypes. All of the observed cellular phenotypes were rescued in CRISPR-Cas9 generated isogenic controls, indicating a clear connection to the mutation. Moreover, mitochondria deficits, metabolic disturbances and synaptic deficiencies are considered early disease phenotypes, which can be recapitulated in our in vitro patient specific disease models making them attractive for drug target development for early interventions.