Advancing Brain Regeneration Therapies
Dan Lewis Foundation | Summer 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.


  1. Schwab, M. E. & Strittmatter, S. M. Nogo limits neural plasticity and recovery from injury. Curr. Opin. Neurobiol. 27, 53–60 (2014).
  2. Lindborg, J. A. et al. Optic nerve regeneration screen identifies multiple genes restricting adult neural repair. Cell Rep. 34, 108777 (2021).
  3. Maimon, R. et al. Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB. Nat. Neurosci. 24, 1089–1099 (2021).
  4. Kim, J.-T. et al. Human embryonic stem cell-derived cerebral organoids for treatment of mild traumatic brain injury in a mouse model. Biochem. Biophys. Res. Commun. 635, 169–178 (2022).
  5. Lust, K. et al. Single-cell analyses of axolotl telencephalon organization, neurogenesis, and regeneration. Science 377, eabp9262 (2022).
  6. Chrostek, M. R. et al. Efficacy of Cell-Based Therapies for Traumatic Brain Injuries. Brain Sci 9, (2019).
  7. Fischer, I., Dulin, J. N. & Lane, M. A. Transplanting neural progenitor cells to restore connectivity after spinal cord injury. Nat. Rev. Neurosci. 21, 366–383 (2020).
  8. Wang, Z. et al. Cerebral organoids transplantation improves neurological motor function in rat brain injury. CNS Neurosci. Ther. 26, 682–697 (2020).
  9. van Dyck, L. I. & Morrow, E. M. Genetic control of postnatal human brain growth. Curr. Opin. Neurol. 30, 114–124 (2017).
  10. Harris, K. M. Structural LTP: from synaptogenesis to regulated synapse enlargement and clustering. Curr. Opin. Neurobiol. 63, 189–197 (2020).
  11. Simon, C., Bolton, D. A. E., Kennedy, N. C., Soekadar, S. R. & Ruddy, K. L. Challenges and Opportunities for the Future of Brain-Computer Interface in Neurorehabilitation. Front. Neurosci. 15, 699428 (2021).
  12. Samejima, S. et al. Brain-Computer-Spinal Interface Restores Upper Limb Function After Spinal Cord Injury. IEEE Trans. Neural Syst. Rehabil. Eng. 29, 1233–1242 (2021).
A gold trophy with a laurel wreath around it.
By Dan Lewis Foundation April 2, 2025
For the third consecutive year, the Dan Lewis Foundation for Brain Regeneration is proud to announce the DLF Prize competition. The 2025 DLF Prize, a $20,000 award, will recognize an outstanding early career scientist (2 to 5 years post-doc) conducting innovative research in neuroscience, pharmacology, or biotechnology. This prestigious prize honors researchers whose work aligns with the DLF mission to drive breakthroughs in neural regeneration and repair. The current research priorities of the DLF are: Pharmacological Reactivation of Neural Repair: Research into pharmacological methods of reactivating or augmenting synaptogenesis, neurogenesis or axonal repair. Cell-Based Cortical Repair: Investigating the potential of derived cortical neurons to restore function in damaged cortical regions. Transcriptomics of Neural Recovery: Characterizing transcriptomic profiles of cortical neurons in the recovery phase following brain injury to identify pathways that drive repair. Molecular Inhibitor Targeting: Advancing anti-sense oligonucleotides (ASO’s) or small-molecule therapeutics designed to downregulate inhibitors of neural regeneration in the cortex or spinal cord. Application for the 2025 DLF Prize can be made by going to our website— danlewisfoundation.org —and clicking on the Tab “ 2025 DLF Prize ”. This will bring you into the application portal. The application portal opened in March, 2025 and will remain open through May 31st. Once in the portal, you will find complete information about the DLF prize, eligibility requirements, and an application form which can be filled in and submitted online. The winner of the 2023 DLF Prize, Dr. Roy Maimon, continues his research indicating that downregulation of PTBP1, an RNA-binding protein, can convert glial cells into neurons in the adult brain (Maimon et al. 2024) .* Dr. Maimon, currently a post-doc at the University of California, San Diego is currently interviewing for a faculty position at several prominent neuroscience departments. The winner of the 2024 DLF Prize, Dr. William Zeiger is a physician-scientist in the Department of Neurology, Movement Disorders Division, at UCLA. Dr. Zeiger has expertise in interrogating neural circuits using a classic “lesional neurology” approach. He states, “Our lab remains focused on understanding how neural circuits become dysfunctional after lesions to the cortex and on investigating novel circuit-based approaches to reactivate and restore damaged cortex”. * Maimon, Roy, Carlos Chillon-Marinas, Sonia Vazquez-Sanchez, Colin Kern, Kresna Jenie, Kseniya Malukhina, Stephen Moore, et al. 2024. “Re-Activation of Neurogenic Niches in Aging Brain.” BioRxiv. https://doi.org/10.1101/2024.01.27.575940.
By Dan Lewis Foundation April 2, 2025
Alan was injured in 2021, at age 42. An art teacher in Lakewood, Colorado, Alan was riding his bicycle after school and was crossing at an intersection when a truck turned into the crosswalk area and hit him. Alan reports no memory of the event but has been told this is what happened. Alan says “My frontal lobe took the brunt of the impact, particularly the left frontal lobe”. Alan had a 2 ½ week stay at a nearby hospital where he, “re-learned to talk, to walk, and drink”-- although again he reports no memory of his stay there. Alan was then transferred to Craig Rehabilitation Hospital, in Englewood, Colorado. Alan says, “The only reason I knew I was at Craig is that I rolled over in bed and saw “Welcome to Craig” on the dry erase board.” During this stage of recovering, Alan repeatedly denied that he had been in an accident. Twice he tried to leave Craig on his own accord despite his wife’s and his therapists’ assurances that it was important for him to stay to recuperate from his injuries. Alan’s wife was 8 months pregnant at the time of his accident and gave birth to their son while Alan was an inpatient at Craig. Alan’s wife brought his newborn son to visit him days after the birth and Alan held him while sitting in his wheelchair, but Alan wistfully reports this is another thing he can’t remember. Alan reports that he still has significant difficulties with memory. Alan has also experienced several other neuropsychological difficulties. He states that for months after his injury, he could not experience emotion. “I could not laugh, I couldn’t cry.” Even after three years, his emotional experience is constricted. However, an emotion that is sometimes elevated is irritation and anger. Sometimes, dealing with people can be difficult because he may have temper flare-ups with little reason. This is something that Alan regrets and he is working hard with his neuropsychologist to improve the regulation of his emotions. Alan also has difficulty with organization, motivation, and distractibility. Earlier in his recovery, he had trouble sequencing and had difficulty carrying out personal and household routines. Alan has benefited greatly from therapy and his own hard work to make improvements in these areas. A chief reason that Alan works so hard in his recovery is so that he can be a good father to his son who is now almost 3 years old. He recognizes that it is important not to get frustrated when it seems that he can’t provide what his son wants or needs at a given moment. “I’m trying to raise my son the best I can…he’s at such a pivotal time in his life.” Alan’s financial situation was helped for a time by Social Security Disability Insurance payments but these payments ended. He is trying to get SSDI reinstated but the process of doing so is confusing and is taking a lot of time. Alan returned to work about 11 months ago at a liquor store (after about 2 years of not being able to work), the same store where he previously worked part time while teaching. He works in the wine department. “I sell wine and make recommendations.” When asked for advice to other brain injury survivors, Alan’s words were: “No matter how confused or upset you are or how frustrated you get, keep pressing on and moving forward because there is light at the end of the tunnel even though it may seem long. Keep moving forward and don’t give up no matter what anyone says to you”. Alan added that supports for individuals with brain injury are very important. He has found support groups, retreats, and seminars/events where brain injury survivors can share their experience to be very helpful. The volunteer work he does at Craig Hospital has been valuable for him. Alan is an inspiring individual. Despite having scarce memory of his accident and some confusion about the functional losses he has experienced, Alan has worked hard to make his recovery as complete as possible. He continues to work hard to progress and to express gratitude for those who have assisted him along the way.