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Open for Hope! A Spring 2024 TBI Research Update

How and why to enroll in FDA-authorized, DoD-backed research using Hope Bio's cells in TBI | Written by Jan Shultis

Last year, Hope Biosciences was privileged to announce a four-year, nearly $5 million clinical trial grant awarded by the Department of Defense’s Office of Congressionally Directed Medical Research Programs (CDMRP) to evaluate if intravenously infused Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) reduce chronic neuroinflammatory response to severe traumatic brain injury (TBI).

 

Hope Biosciences with the team at UTHealth Houston

Led by UTHealth Houston and industry partner Hope Biosciences, the award is a significant positive step toward developing treatment for a currently incurable condition that affects approximately 1.5 million Americans every year, killing 50,000 annually. The Centers for Disease Control reports an estimated 5.3 million people live with permanent TBI-related disability in the U.S. More than 460,000 military service members have been diagnosed with TBI since 2000. Scientist reviewers lauded the project’s potential to fill a current void in effective interventions for chronic TBI and noted potential for major impact on military health, including combat-incurred blast injuries, as well as civilian mechanisms such as motor vehicle crashes, falls, and other impacts.

 

TBI trial status update

 

UTHealth Houston's Clinical Research Unit

Enrollment has begun for this clinical trial, a 51-participant, FDA-authorized double-blind placebo-controlled Phase II protocol dictating three infusions of approximately 200 million autologous stem cells cultured through Hope Biosciences’ proprietary technology, administered over a six-week period and spaced 14 days apart. Fifty-one participants will be enrolled from two clinical sites in Houston and San Antonio, Texas. Participants can be male or female, between 18 and 55 years of age, with functional damage from closed head trauma unlikely to improve with present standard of care approaches. Onset or diagnosis must be greater than six months, with a Glasgow Outcome Scale-Extended score greater than “2” and less than or equal to “6” (The Glasgow Scale describes level of consciousness and extent of impaired consciousness after trauma. It measures responsiveness of eye-opening, motor, and verbal control as measures of the three requirements of consciousness in a medical context – that is, a person must be awake, alert, and oriented to be considered conscious. A score in the low range of 2-6 is indicative of severe TBI.) Participants must be able to communicate in English or Spanish. There is no cost to participate. Find the complete trial listing (NCT05951777) on clinicaltrials.gov


This study marks the second collaboration between UTHealth and Hope Biosciences. Preliminary results of a recently completed 24-patient open label Phase I/IIa clinical trial in TBI (NCT04063215) demonstrated the potential of reducing chronic neuroinflammation, yielding clinically significant effects in imaging, biomarkers, and patient-reported outcomes. Initial findings were presented during the Cellular Therapies and Transfusion Medicine in Trauma and Critical Care (CTTACC) 2023 Conference in Scottsdale, Arizona.

 

Fit the criteria, and wondering whether this clinical trial is a good fit for you or a loved one? Keep reading to learn more about why we believe mesenchymal cell therapy is the ideal therapeutic for brain injury.



 

The nature of traumatic brain injury

 

The need for personalized medicine in TBI is pressing, great, and increasingly recognized. So, too, is the need for therapeutics capable of acting on multiple systems simultaneously.[1] Quality-of-life questions are demanding, nuanced, and real, especially in cases of severe TBI, of which more than 20% of cases lead to severe disability, vegetative state, and/or death.[2]

 

As one prominent textbook explains, in instances of TBI:

 

“A specific temporal order of events at the cellular and molecular level occurs in response to primary impact forces when applied to the neuraxis. TBI initiates secondary reactive biochemical, molecular and genetic responses that may be autodestructive or neuroprotective. Therefore neurotrauma has effects on cell membranes, ion channels of axons, neurons and astrocytes, and also on whole brain systems affecting substrate delivery, blood flow, brain metabolism and neurological function.”[3]


In other words, a traumatic brain injury is such a significant event that it can impact not only the injury site, but also the systems and functions of our brains, down to a cellular level. The exact effects of traumatic impact on the brain’s various membranes, cellular components, and neurotransmitters is generally not yet well understood. Most mechanistic research undertaken today is in animal studies.

 

In humans, we know TBI is highly individualized. While circumstances may be similar and effects can follow patterns, no two injuries are exactly alike. In closed head trauma (that means, instances where there are no open wounds to the head), the extent of damage is often directly linked to degree of movement of the brain within the cranium. A myriad of biomechanical modeling techniques have been and are being employed to better understand the way forces, or combinations of forces, act on specific areas of the brain. The intricate delicacy of the brain, the organ being acted upon in an injurious way, adds additional layers of nuance. Symptomology is varied and can be vast and involve the vascular, endocrine, metabolic, and other systems.

 

Considering its staggering complexity, how, then, can modern science develop standard foundations to treating brain injury?

 

That’s where Hope Bio comes in. Hope’s proprietary culturing technology guarantees repeatable, high volume MSC therapies throughout the continuum of TBI, in cases from mild to acute.

 

 

The hope of mesenchymal stem cell therapy


Cell therapy is a direct and seemingly linear answer to the need for personalized interventions in complex conditions such as TBI. Cell therapy is a form of regenerative medicine, a term referring to scientific efforts to restore diseased or injured tissues or organs by supporting the body in its natural processes whenever and to the greatest extent possible, rather than implanting devices or engineered parts that may require years of stringent pharmaceutical support before ultimately failing.[4] [5]  “Cell therapy” specifically denotes the practice of transferring cellular material into a person for medical purposes.[6] Stem cells are an unspecialized type of cell that can transform into a variety of specialized cell types in the body. For example, a stem cell might be capable of becoming a liver cell, brain cell, heart cell, and so on, if exposed to the necessary stimuli and conditions. Stem cells also have potential to divide for an indefinite period, which means they can make many copies of both themselves and differentiated cells. Stem cells “work” by realizing their potential and becoming other cell types when, where, and as needed by the body, making them particularly promising in complex conditions that affect multiple bodily symptoms, like TBI, and in conditions of indeterminable causation.



 

Any treatment intended to work in the brain must either be administered directly into the brain, or capable of passing through the blood-brain barrier, a semi-permeable cellular membrane that tightly controls what gets into the brain space. There is evidence that the barrier’s function is transiently disturbed as a result of impact trauma such as TBI,[7] adding yet another layer to the complexities of treatment.


Hope Biosciences during the stem cell culturing process

Hope Biosciences banks, cultures, and supports FDA-authorized studies using mesenchymal stem cells (MSCs)[8] taken from adipose (fat) tissue and cultured through proprietary technology. Hope Bio’s cells are identified in literature as “HB-adMSCs” (Hope Biosciences’ adipose-derived mesenchymal stem cells). MSCs are a specific cell type; multipotent adult stem cells[9] capable of making many other types of tissue cells and contributing to physiological processes in myriad ways. MSCs can differentiate into various local cell types at injured sites, secrete growth factors that help in tissue regeneration, produce new secretory pathways at a cellular level, and effectively communicate with stressed or injured somatic cells to transfer their cytoplasmic elements and organelles.[10] Several studies have revealed that in addition to their ability to differentiate into different cell types, MSCs may also exert therapeutic effects through cell "enhancement," which generally means the production and release of trophic and anti-inflammatory factors whose therapeutic effects may help to restore the body's natural physiological environment. Furthermore, MSCs have a function in the modulation of the inflammatory and immunological responses in the body. Equally important in TBI, MSCs are capable of penetrating the blood brain barrier.[11]

 

Introduction of stem cells can stimulate continued regeneration. Once in the body, MSCs have a documented homing ability; that is, they migrate to injured tissues in areas the body tells the stem cells are in need, whether that need is apparent on anything larger than a cellular level yet or not. Tactically, this homing ability means that MSC therapy can introduce cells into the body through intravenous infusion, a minimally invasive process and one ideally accessible to medically fragile patients, such as patients with severe TBI. The cells can be trusted, if we want to think of it that way, to end up where and as most needed, whether that need is visible to external physicians and researchers or not.[12] MSC research has been conducted for at least 50 years, and MSC therapy has an established and accepted safety profile.

 



 

In sum…

 

Like the DoD’s scientific reviewers of this TBI trial, and our academic and hospital partners, Hope Biosciences believes in the potential of HB-adMSCs to improve quality of life and all previously stated markers associated with improvement in cases of severe TBI. This conversation started as a research update and enrollment announcement, and we’ll close with the same appeal – if you or a loved one meet the eligibility criteria previously presented, please reach out. There is hope for healing from TBI.


 

About Hope Biosciences

Hope Biosciences is a biopharmaceutical company developing adult stem cell therapeutics for a variety of clinical indications, and the only clinical grade adult stem cell banking facility in the nation serving both adults and newborns. Hope Biosciences occupies a unique position in the regenerative medicine space, noteworthy both for patented cell culture methods and effectiveness getting cells to patients through robust collaboration with academic and clinical research organizations. Hope’s proprietary cell culturing process makes Hope Biosciences the gold standard in producing high volume, consistent, repeatable mesenchymal stem cells for clinical purposes. Hope Biosciences actively partners with organizations and teams in need of cellular products for in vitro, preclinical, and clinical projects.

 

Headquartered in Sugar Land, Texas and now in its eighth year of operation, to date stem cells cultured at Hope Biosciences have been used in more than 35 FDA-authorized clinical studies covering a wide range of conditions including chronic injury, degenerative diseases, and autoimmune diseases.

 

Learn more about Hope Biosciences at www.hope.bio.




 

[1] Many professionals in the TBI field recognize a pressing need for therapeutics with potential for neuropsychiatric support. Though the mechanistic discussion of how and why MSCs can provide such support exceed the scope of the current conversation, a growing body of research demonstrates their promise.

[2] Simon Fleminger and Jennie Ponsford. “Long term outcome after traumatic brain injury.” BMJ. 2005 Dec 17; 331 (7530): 1419-1420. DOI: 10.1136/bmj.331.7530.1419.

[3] Ross Bullock and Narendra Nathoo. “Injury and Cell Function.” Head Injury: Pathophysiology and Management. Second Ed. Peter Reilly and Ross Bullock, ed. Oxford University Press (New York, 2005), 113.

[4] See Chris Mason and Peter Dunnill’s opinion editorial “A Brief Definition of Regenerative Medicine” in Regenerative Medicine, 2008 (3)1, 1-5.

[5] Mao AS, Mooney DJ. Regenerative medicine: Current therapies and future directions. Proc Natl Acad Sci U S A. 2015 Nov 24;112(47):14452-9. doi: 10.1073/pnas.1508520112. PMID: 26598661; PMCID: PMC4664309.

[6] El-Kadiry AE, Rafei M, Shammaa R. Cell Therapy: Types, Regulation, and Clinical Benefits. Front Med (Lausanne). 2021 Nov 22;8:756029. doi: 10.3389/fmed.2021.756029. PMID: 34881261; PMCID: PMC8645794.

[7] Ross Bullock and Narendra Nathoo. “Injury and Cell Function.” Head Injury: Pathophysiology and Management. Second Ed. Peter Reilly and Ross Bullock, ed. Oxford University Press (New York, 2005), 116.

[8] Debate continues over which words best describe MSCs, whose functions mechanistic researchers continue to learn about. Common monikers include “Mesenchymal Stem Cell,” “Mesenchymal Stromal Cell,” and “Medicinal Signaling Cell.”  HBSCRF holds “mesenchymal stem cells” to be defensible and accurate.

[9] Academic debate persists surrounding the technical status of MSCs as “pluripotent” or “multipotent.” As of this writing, academia tends to use “multipotent,” while semi-popular and popular writing trends toward use of “pluripotent.” We will use the term “multipotent” for this conversation, though arguing the terminology is not of great concern for this conversation – the capabilities of the stem cells remain as they are, no matter how we categorize them at this juncture in scientific discovery.

[10] N. Attia, et al., “Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects,” Pharmaceutics 13, no.6 (2021): 843. https://doi.org/10.3390/pharmaceutics13060843

[11] A. Weiss & M.H. Dahlke, “Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs,” Frontiers in immunology 10 (2019): 1191. https://doi.org/10.3389/fimmu.2019.01191

[12] S. Kim, et al., “The Preventive Therapeutic Effects of Intravenous Human Adipose-Derived Stem Cells in Alzheimer’s Disease Mice,” (2012). https://doi.org/10.1371/journal.pone.0045757

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