Neurotrophic Growth Factors for the Treatment of Amyotrophic Lateral Sclerosis: Where Do We Stand?

Overview

Journal Front Neurosci

Date 2010 Jul 2

PMID 20592948

Citations 55

Authors

Alexandre Henriques

Claudia Pitzer

Armin Schneider

Affiliations

Soon will be listed here.

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive loss of motoneurons, motor weakness and death within 3-5 years after disease onset. Therapeutic options remain limited despite substantial number of approaches that have been tested clinically. Many neurotrophic growth factors are known to promote the survival of neurons and foster regeneration in the central nervous system. Various neurotrophic factors have been investigated pre-clinically and clinically for the treatment of ALS. Although pre-clinical data appeared promising, no neurotrophic factors succeeded yet in a clinical phase III trial. In this review we discuss the rationale behind those factors, possible reasons for clinical failures, and argue for a renewal of hope in this powerful class of drugs for the treatment of ALS.

Citing Articles

VEGF expression disparities in brainstem motor neurons of the SOD1 ALS model: Correlations with neuronal vulnerability.

Silva-Hucha S, Fernandez de Sevilla M, Humphreys K, Benson F, Franco J, Pozo D Neurotherapeutics. 2024; 21(3):e00340.

PMID: 38472048 PMC: 11070718. DOI: 10.1016/j.neurot.2024.e00340.

Targeting synapse function and loss for treatment of neurodegenerative diseases.

Dejanovic B, Sheng M, Hanson J Nat Rev Drug Discov. 2023; 23(1):23-42.

PMID: 38012296 DOI: 10.1038/s41573-023-00823-1.

Therapeutic Effects of Combination of Nebivolol and Donepezil: Targeting Multifactorial Mechanisms in ALS.

Lee S, Cho H, Oh J, Park J, Bae S, Park H Neurotherapeutics. 2023; 20(6):1779-1795.

PMID: 37782409 PMC: 10684847. DOI: 10.1007/s13311-023-01444-7.

Persistent NRG1 Type III Overexpression in Spinal Motor Neurons Has No Therapeutic Effect on ALS-Related Pathology in SOD1 Mice.

Hernandez S, Salvany S, Casanovas A, Piedrafita L, Soto-Bernardini M, Tarabal O Neurotherapeutics. 2023; 20(6):1820-1834.

PMID: 37733208 PMC: 10684470. DOI: 10.1007/s13311-023-01424-x.

Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives.

Najafi S, Najafi P, Farkhad N, Hosseini Torshizi G, Assaran Darban R, Boroumand A Iran J Basic Med Sci. 2023; 26(8):872-881.

PMID: 37427325 PMC: 10329242. DOI: 10.22038/IJBMS.2023.66364.14572.

References

Blackburn D, Sargsyan S, Monk P, Shaw P . Astrocyte function and role in motor neuron disease: a future therapeutic target?. Glia. 2009; 57(12):1251-64. DOI: 10.1002/glia.20848. View

Fisher M, Albers G, Donnan G, Furlan A, Grotta J, Kidwell C . Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable. Stroke. 2005; 36(8):1808-13. DOI: 10.1161/01.STR.0000173403.60553.27. View

Lo D . Instructive roles of neurotrophins in synaptic plasticity. Prog Brain Res. 1999; 117:65-70. DOI: 10.1016/s0079-6123(08)64008-x. View

Ebendal T, Bengtsson H, Soderstrom S . Bone morphogenetic proteins and their receptors: potential functions in the brain. J Neurosci Res. 1998; 51(2):139-46. DOI: 10.1002/(SICI)1097-4547(19980115)51:2<139::AID-JNR2>3.0.CO;2-E. View

Fisher M, Feuerstein G, Howells D, Hurn P, Kent T, Savitz S . Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke. 2009; 40(6):2244-50. PMC: 2888275. DOI: 10.1161/STROKEAHA.108.541128. View

Gordon P, Cheng B, Montes J, Doorish C, Albert S, Mitsumoto H . Outcome measures for early phase clinical trials. Amyotroph Lateral Scler. 2007; 8(5):270-3. DOI: 10.1080/17482960701547958. View

Xiao Q, Zhao W, Beers D, Yen A, Xie W, Henkel J . Mutant SOD1(G93A) microglia are more neurotoxic relative to wild-type microglia. J Neurochem. 2007; 102(6):2008-2019. DOI: 10.1111/j.1471-4159.2007.04677.x. View

Dobrogowska D, Lossinsky A, Tarnawski M, Vorbrodt A . Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor. J Neurocytol. 2000; 27(3):163-73. DOI: 10.1023/a:1006907608230. View

Ratnaparkhi A, Lawless G, Schweizer F, Golshani P, Jackson G . A Drosophila model of ALS: human ALS-associated mutation in VAP33A suggests a dominant negative mechanism. PLoS One. 2008; 3(6):e2334. PMC: 2390852. DOI: 10.1371/journal.pone.0002334. View

10.

Statler P, McPherson R, Bauer L, Kellert B, Juul S . Pharmacokinetics of high-dose recombinant erythropoietin in plasma and brain of neonatal rats. Pediatr Res. 2007; 61(6):671-5. DOI: 10.1203/pdr.0b013e31805341dc. View

11.

Scott S, Kranz J, Cole J, Lincecum J, Thompson K, Kelly N . Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler. 2008; 9(1):4-15. DOI: 10.1080/17482960701856300. View

12.

Martinez H, Gonzalez-Garza M, Moreno-Cuevas J, Caro E, Gutierrez-Jimenez E, Segura J . Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. Cytotherapy. 2009; 11(1):26-34. DOI: 10.1080/14653240802644651. View

13.

Van Den Bosch L, Tilkin P, Lemmens G, Robberecht W . Minocycline delays disease onset and mortality in a transgenic model of ALS. Neuroreport. 2002; 13(8):1067-70. DOI: 10.1097/00001756-200206120-00018. View

14.

Strom A, Gal J, Shi P, Kasarskis E, Hayward L, Zhu H . Retrograde axonal transport and motor neuron disease. J Neurochem. 2008; 106(2):495-505. PMC: 4477783. DOI: 10.1111/j.1471-4159.2008.05393.x. View

15.

Shefner J, Cudkowicz M, Zhang H, Schoenfeld D, Jillapalli D . The use of statistical MUNE in a multicenter clinical trial. Muscle Nerve. 2004; 30(4):463-9. DOI: 10.1002/mus.20120. View

16.

Pan H, Wu H, Cheng F, Chen C, Sheu M, Chen C . Potentiation of angiogenesis and regeneration by G-CSF after sciatic nerve crush injury. Biochem Biophys Res Commun. 2009; 382(1):177-82. DOI: 10.1016/j.bbrc.2009.03.003. View

17.

Kastin A, Akerstrom V, Pan W . Glial cell line-derived neurotrophic factor does not enter normal mouse brain. Neurosci Lett. 2003; 340(3):239-41. DOI: 10.1016/s0304-3940(03)00007-7. View

18.

Yan Q, Elliott J, Snider W . Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992; 360(6406):753-5. DOI: 10.1038/360753a0. View

19.

Lepore A, Haenggeli C, Gasmi M, Bishop K, Bartus R, Maragakis N . Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS. Brain Res. 2007; 1185:256-65. PMC: 2265207. DOI: 10.1016/j.brainres.2007.09.034. View

20.

Caraganis A, Benn S, Cudkowicz M, Brown Jr R . Thrombopoietin is ineffective in a mouse model of motor neuron disease. Amyotroph Lateral Scler. 2008; 9(6):354-8. DOI: 10.1080/17482960802103040. View