Towards Brain Regeneration and Functional Recovery
Dan Lewis Foundation | Fall 2022

A major brain injury can result in the loss of brain tissue, the disruption of connections among regions of the nervous system, the destruction of specific brain regions that control various functions or sensations, and the creation of chaotic electrical activity that disrupts other brain signaling. 


To maximize healing in the damaged brain, minimizing the impact of the initial injury in the early hours and days after the trauma is essential. Bleeding and swelling must be controlled. Ongoing damage and scarring of the brain as a result of inflammation and disruption of blood vessels must be limited. Metabolic damage from uncontrolled seizures must be reduced.


Eventually, the storm of the acute events subsides. A person who survives the initial injury enters a future with residual damage and loss of function. Although other tissues and organs are capable of regeneration, human brain tissue does not regrow after damage. Some functional recovery can occur over time, mainly as the person retrains surviving brain regions to take over functions that were served by the injured or disrupted neural tissue. Persons who have survived a severe brain injury usually experience only modest further improvement in the years after their injury.


Recent research has demonstrated that it is plausible to develop medicines and treatments that stimulate the brain to regenerate itself and allow for functional recovery, even years after a devastating injury. The DLF is committed to focusing on developing therapies that will induce brain regeneration and function in persons living in the chronic phase of traumatic brain damage. 


Our scientific experts believe that a combination of strategies will be required to allow the brain to experience regrowth and recovery. First, it is necessary to unlock the ability of neurons to grow and replace lost brain tissue. Second, the power of the brain to form new synaptic connections must be enhanced, both in surviving brain regions and in regions repopulated with neurons. Third, the ability of neurons to reconnect to severed axons must be enhanced. Fourth, there must be highly targeted methods to train recovering and regenerating brain regions. Finally, novel devices that connect computers directly to neurons in the brain are being developed. These “brain-computer interfaces” are being designed to re-connect surviving brain regions to allow movement in paralyzed limbs and expression to people who can no longer speak. In each issue of the DLF newsletter, we will highlight one aspect of emerging research about stimulating brain regeneration (see Research Review Corner). We hope that growing awareness of dramatic scientific progress will motivate people to help support this work.


The DLF will focus resources and attention on those scientific projects and initiatives that are most likely to yield medicines that will stimulate brain regeneration and functional recovery. The DLF depends on charitable contributions and grants to fund the research, which will make these possibilities a reality. We hope you find these research updates to be informative and inspiring. 

A man is holding a fish in his hand in front of a lake.
By Dan Lewis Foundation November 6, 2024
After a life-altering accident in October 2022, Devon Guffey’s story is about resilience and determination. His journey has been profiled in the summer 2023 issue of the Making Headway Newsletter: https://www.danlewisfoundation.org/devons-story . Hit by a drunk driver, Devon sustained severe brain and physical injuries, including axonal shearing, a traumatic frontal lobe injury, and facial fractures. Even after contracting meningitis while in a coma, Devon fought hard to survive – and today, his recovery continues to inspire us all. In late 2023, Devon worked as an assistant basketball coach at Blue River Valley, where he had once been a student. His love for sports and dedication to regaining his physical strength returned him to the gym, where his hard work paid off. Devon’s persistence earned him another job at the YMCA, guiding gym members and supporting facility upkeep. Through all the challenges—deafness in one ear, blindness in one eye, and a permanent loss of taste and smell—Devon perseveres. He recently regained his driving license, a significant milestone that symbolizes his increasing independence and cognitive and physical recovery. While each day may not show significant changes, Devon now sees his progress over time. Today, Devon speaks to groups about his journey, the dangers of drunk driving, and finding strength in adversity. His message is clear: recovery is a process, and sometimes, "can't" simply means "can't do it yet ." Every TBI is unique, and Devon’s story powerfully reminds us of the strength that comes from resilience and community. We are grateful to Devon for continuing to share his story and for his role in uplifting others facing difficult paths. His journey is a testament to the fact that we are stronger together. #BrainInjuryAwareness #DevonsJourney #Resilience #EndDrunkDriving #MakingHeadway
A close up of a brain with a lot of cells and a purple background.
By Dan Lewis Foundation | Summer 2024 July 10, 2024
Scientists worldwide are working to find ways to stimulate healing and functional recovery after severe brain injuries. This work is driven by the desperate needs of persons who have suffered brain damage. It is inspired by the knowledge that the information required to create new brain cells, cause these cells to interconnect, and stimulate new learning is contained in our genome. Now that we can readily generate stem cells from adult tissue, we have access to the genomic program that can control all of the intricate details of brain tissue formation. A number of different research themes are being pursued productively. These include: (1) enabling injured neurons to self-repair (“axonal repair”) 1,2 ; (2) replacing damaged tissue by increasing the growth of new neurons (“neurogenesis”) 3-5 ; (3) transplanting new brain cells that are derived from a person’s own stem cells (“autologous cellular repletion”) 6-8 ; (4) stimulating the re-wiring of new or surviving tissue by encouraging the formation of new connections (“synaptogenesis”) 9,10 ; and (5) augmenting the function of a damaged brain by the use of bio-computational prostheses (“brain-computer interfaces”) 11,12 ; We’ve explored these themes in previous newsletters. The goal of stimulating meaningful brain regeneration is now sufficiently plausible that a large-scale, well-funded campaign needs to be funded to bring meaningful new therapies to patients within the foreseeable future. Here, we suggest a high-level outline of the research themes for such a campaign. A ‘moon shot’ program towards brain regeneration would leverage cutting-edge technologies in stem cell research, gene therapy, synaptic plasticity, neuronal repair, and brain-computer interfaces (BCIs) to develop innovative treatments for brain injuries and neurodegenerative diseases. These treatments would target the restoration of lost brain functions and improvement in the quality of life for individuals affected by severe brain injuries. This research agenda aims to catalyze serious discussion about creating a federal program with funding, organizational resources, and expert governance to enable brain regeneration in our lifetimes. Major Themes For a Brain Regeneration “Moon Shot” Program 1: Promote the formation of new neurons 1.1 Stimulate the brain to create new neurons 1.2 Create new neurons from patient-derived induced pluripotent stem cells to be transplanted back into the patient. Create new glial cells to support neurogenesis. 2: Stimulate new synaptic formation 2.1 Develop drugs that enhance synaptic plasticity and promote the formation of new synaptic connections 3: Stimulate self-repair of damaged neurons 3.1 Develop drugs that de-repress neurons and, thereby, enable axonal regrowth 4: Develop brain-computer interfaces (BCIs) for brain-injured patients 4.1: Develop and test BCIs that enable the brain to control behaviors or external devices and, thereby, augment or replace impaired functions. 4.2: Develop and test BCIs that can accelerate the training of remapped brain tissue in persons with brain injuries to optimize functional recovery. 4.3: Combine BCIs with other strategies (e.g., cell repletion, synaptogenesis, and enhanced plasticity) to accelerate adaptation and functional improvement. The proposed research themes can underpin targeted research to stimulate meaningful brain regeneration, offering new hope for patients with brain injuries and neurodegenerative diseases. While the scientific challenges are profound, there has been sufficient progress to justify substantial investment in brain regeneration research. Any such large-scale program will require coordinated collaborations among academic and commercial partners, skillful governance and management, and a shared sense of profound commitment to the goal. The recent pace of advances in cell biology, stem cell technology, bio-computational interfaces, and genomically targeting medicines suggests that large-scale investment will yield meaningful clinical advances toward brain regeneration after injury. With robust funding and skilled leadership, this comprehensive research agenda has a realistic potential to transform scientific breakthroughs into tangible medical therapies, offering hope to millions affected by brain damage.
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