Kioutchoukova IP, Foster DT, Thakkar RN, Foreman MA, Burgess BJ, Toms RM, Molina Valero EE, Lucke-Wold B. Neurologic orphan diseases: Emerging innovations and role for genetic treatments. World J Exp Med 2023; 13(4): 59-74 [PMID: 37767543 DOI: 10.5493/wjem.v13.i4.59]
Corresponding Author of This Article
Brandon Lucke-Wold, MD, PhD, Neurosurgeon, Department of Neurosurgery, University of Florida, 1505 SW Archer Rd, Gainesville, FL 32611, United States. brandon.lucke-wold@neurosurgery.ufl.edu
Research Domain of This Article
Neurosciences
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Exp Med. Sep 20, 2023; 13(4): 59-74 Published online Sep 20, 2023. doi: 10.5493/wjem.v13.i4.59
Neurologic orphan diseases: Emerging innovations and role for genetic treatments
Ivelina P Kioutchoukova, Devon T Foster, Rajvi N Thakkar, Marco A Foreman, Brandon J Burgess, Rebecca M Toms, Eduardo E Molina Valero, Brandon Lucke-Wold
Ivelina P Kioutchoukova, Rajvi N Thakkar, Marco A Foreman, Brandon J Burgess, Rebecca M Toms, Eduardo E Molina Valero, College of Medicine, University of Florida, Gainesville, FL 32611, United States
Devon T Foster, Florida International University Herbert Wertheim College of Medicine, Florida International University Herbert Wertheim College of Medicine, Miami, FL 33199, United States
Brandon Lucke-Wold, Department of Neurosurgery, University of Florida, Gainesville, FL 32611, United States
Author contributions: Lucke-Wold B contributed to conceptualization and supervision; Kioutchoukova I, Foster D, Thakkar R, Foreman M, Burgess B, Toms R, Valero EM contributed to writing-original draft presentation; Ivelina Kioutchoukova, Devon Foster contributed to writing-editing and review.
Conflict-of-interest statement: All the authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Brandon Lucke-Wold, MD, PhD, Neurosurgeon, Department of Neurosurgery, University of Florida, 1505 SW Archer Rd, Gainesville, FL 32611, United States. brandon.lucke-wold@neurosurgery.ufl.edu
Received: June 17, 2023 Peer-review started: June 17, 2023 First decision: July 4, 2023 Revised: July 16, 2023 Accepted: August 11, 2023 Article in press: August 11, 2023 Published online: September 20, 2023 Processing time: 89 Days and 15 Hours
Abstract
Orphan diseases are rare diseases that affect less than 200000 individuals within the United States. Most orphan diseases are of neurologic and genetic origin. With the current advances in technology, more funding has been devoted to developing therapeutic agents for patients with these conditions. In our review, we highlight emerging options for patients with neurologic orphan diseases, specifically including diseases resulting in muscular deterioration, epilepsy, seizures, neurodegenerative movement disorders, inhibited cognitive development, neuron deterioration, and tumors. After extensive literature review, gene therapy offers a promising route for the treatment of neurologic orphan diseases. The use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several diseases. Additionally, the use of adeno-associated viral vectors has shown improvement in survival, motor function, and developmental milestones, while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia patients. Antisense oligonucleotides have also been used in some neurologic orphan diseases with positive outcomes. Mammalian target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth, proliferation, and angiogenesis. Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.
Core Tip: Neurologic orphan diseases are rare conditions that impact a small percentage of the population. Through new advances in technology and research, the use of genetic treatment for these conditions is increasing. Recent advances in clustered regularly interspaced palindromic repeats/Cas9, adeno-associated viral vectors, antisense oligonucleotides, and mammalian target of rapamycin inhibitors have shown improvements in the care of patients and their quality of life.
