Regenerative medicine for neurological diseases—will regenerative neurosurgery deliver?BMJ 2021; 373 doi: https://doi.org/10.1136/bmj.n955 (Published 23 June 2021) Cite this as: BMJ 2021;373:n955
- Terry C Burns, associate professor of neuroscience and neurosurgery1,
- Alfredo Quinones-Hinojosa, professor of neurosurgery2
- 1Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
- 2Neurosurgery Head and Neck Cancer Center, Mayo Clinic, Jacksonville, FL, USA
- Correspondence to Terry C Burns,
Regenerative medicine aspires to transform the future practice of medicine by providing curative, rather than palliative, treatments. Healing the central nervous system (CNS) remains among regenerative medicine’s most highly prized but formidable challenges. “Regenerative neurosurgery” provides access to the CNS or its surrounding structures to preserve or restore neurological function. Pioneering efforts over the past three decades have introduced cells, neurotrophins, and genes with putative regenerative capacity into the CNS to combat neurodegenerative, ischemic, and traumatic diseases. In this review we critically evaluate the rationale, paradigms, and translational progress of regenerative neurosurgery, harnessing access to the CNS to protect, rejuvenate, or replace cell types otherwise irreversibly compromised by neurological disease. We discuss the evidence surrounding fetal, somatic, and pluripotent stem cell derived implants to replace endogenous neuronal and glial cell types and provide trophic support. Neurotrophin based strategies via infusions and gene therapy highlight the motivation to preserve neuronal circuits, the complex fidelity of which cannot be readily recreated. We specifically highlight ongoing translational efforts in Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and spinal cord injury, using these to illustrate the principles, challenges, and opportunities of regenerative neurosurgery. Risks of associated procedures and novel neurosurgical trials are discussed, together with the ethical challenges they pose. After decades of efforts to develop and refine necessary tools and methodologies, regenerative neurosurgery is well positioned to advance treatments for refractory neurological diseases. Strategic multidisciplinary efforts will be critical to harness complementary technologies and maximize mechanistic feedback, accelerating iterative progress toward cures for neurological diseases.
Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors
Contributors: Both authors conceived the scope and content of the manuscript. TCB wrote the manuscript with intellectual contribution from AQH. Both authors critically reviewed the manuscript and approved it for publication. The authors acknowledge the editing assistance of Superior Medical Experts (who assisted in the early draft of the manuscript but had no input into the selection of literature or final wording, and have no commercial links to the subject matter), and Kirsten Burns. Illustration services were provided by Caitlin Mock. Diogo Garcia and Gaetano De Biase provided assistance with preparation of tables. The authors acknowledge many colleagues and collaborators for fruitful discussions, as well as patients whose courageous participation in clinical trials inspire and empower regenerative neurosurgery.
Competing interests: We have read and understood TheBMJ policy on declaration of interests and declare the following interests: TCB serves on the scientific advisory board of Neurametrix and as a consultant for Alector.
In 2020, after the current manuscript was submitted, AHQ became founder of Dome Therapeutics, a company dedicated to stem cell therapies for neurological disorders. The company currently has no products or technologies in development and has no commercial revenue.
Funding: TCB was supported by NIH K12 NRDCP, NINDS NS19770, the Minnesota Partnership for Biotechnology and Genomics, Mayo Clinic Center for Regenerative Medicine, Lucius & Terrie McKelvey, and Regenerative Medicine Minnesota. AQH was supported by the Mayo Clinic Professorship, the Mayo Clinic Clinician Investigator award, the Florida Department of Health Cancer Research Chair Fund, as well as the National Institutes of Health (R43CA221490, R01CA200399, R01CA195503, R01CA216855).
Provenance and peer review: commissioned; externally peer reviewed.