Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy

Lesbordes, Jeanne-Claire; Cifuentes‐Diaz, Carmen; Miroglio, Audrey; Joshi, Vandana; Bordet, Thierry; Kahn, Axel; Melki, Judith

doi:10.1093/hmg/ddg143

Cited by 99 publications

(47 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In spite of the severity of SMA phenotype in mutant mice, CT-1 is able to slow down disease progression. Neuroprotection could be regarded as valuable therapeutic approach in SMA 71 . CT-1 defi ciency causes increased motoneuron cell death in spinal cord and brainstem nuclei of mice during a period between embryonic day 14 and the fi rst postnatal week.…”

Section: Cancermentioning

confidence: 99%

Cardiotrophin-1 Review

Stejskal¹,

Růžička²

2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Section: Cancermentioning

confidence: 99%

Cardiotrophin-1 Review

Stejskal¹,

Růžička²

2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

“…showed that cardiotrophin-1 delivery to SMA mutant mice resulted in protection of proximal and distal motoneurons, which was present even in postnatal period [106]. In this study, cardiotrophin-1 was delivered by intramuscular injection with an adenoviral vector expressing cardiotrophin-1 and it was able to improve survival and delay the motor defect in SMAΔ7 mice in neurons even at low doses.…”

Section: Neurotrophic Compoundsmentioning

confidence: 74%

Treatment strategies for spinal muscular atrophy

Fuller¹,

Barišić

Šešo-Šimić³

et al. 2010

Translational Neuroscience

View full text Add to dashboard Cite

Progress in understanding the genetic basis and pathophysiology of spinal muscular atrophy (SMA), along with continuous efforts in finding a way to increase survival motor neuron (SMN) protein levels have resulted in several strategies that have been proposed as potential directions for efficient drug development. Here we provide an overview on the current status of the following approaches: 1) activation of SMN2 gene and increasing full length SMN2 transcript level, 2) modulating SMN2 splicing, 3) stabilizing SMN mRNA and SMN protein, 4) development of neurotrophic, neuroprotective and anabolic compounds and 5) stem cell and gene therapy. The new preclinical advances warrant a cautious optimism for emergence of an effective treatment in the very near future. Unfortunately, studies indicate that the short half-life of sodium butyrate in human serum does not recommend its use in clinical trials [30]. KeywordsA derivative of sodium butyrate -sodium-4-phenyl-butyrate, also known as phenylbutyrate (PB), was also shown to increase SMN transcript expression, SMN protein and gem counts in fibroblast cells derived from SMA patients [31,32]. It has a well-known pharmacokinetic and safety profile and good penetration into the central nervous system, and so appeared to be a promising candidate for the treatment of SMA. In a small uncontrolled trial an improvement of motor function in 10 SMA type II patients was found after nine weeks of treatment with oral PB, with no apparent major side effects [33]. However, a placebo-controlled trial of intermittent treatment over 13 weeks suggested that there was no improvement in functional scores under the conditions used [34,35]. A phase I/II study initiated by the US Other approachesThe base of treatment in SMA is still supportive care, which requires multidisciplinary medical care [21]. Due to intensive supportive care, such as ventilation, the use of mechanical insufflation-exsufflation device and tube feeding, the survival of patients with SMA type I has significantly increased in recent years [22]. Since forced exercise was found to be of benefit in ALS mouse models [147,148] it was recently studied in SMA mice. Type II SMA mice developed by were used in the interesting study of Grondard et al. [68].The mice were subjected to a training protocol of forced run on a wheel or no training. [1] Botta A., Tacconelli A., Bagni I., Giardina E., Bonifazi E., Pietropolli A., Neurology, 2007Neurology, , 69, 1931Neurology, -1936 [23] Wang C. H., Finkel R. S., Bertini E. S., Schroth M., Simonds A., Wong B.,

show abstract

“…Finally, substances with a neuroprotective action, (such as cardiotrophin-1), 50 and genetic conversion of the SMN 2 gene into SMN 1 , 51 are also the subject of therapeutic proposals being studied.…”

Section: Future Prospects For Diagnosis and Treatment Of Smamentioning

confidence: 99%

Atrofia muscular espinhal: diagnóstico, tratamento e perspectivas futuras

Baioni¹,

Ambiel²

2010

J. Pediatr. (Rio J.)

View full text Add to dashboard Cite

Objective: To report on recent genetic and molecular discoveries and on future prospects for the treatment of spinal muscular atrophy (SMA), thereby helping healthcare professionals to make a quick diagnosis and provide appropriate and timely therapeutic support.Sources: Information was collected from scientific articles published in the last 2 decades, retrieved from the databases SciELO, PubMed, and MEDLINE. Summary of the findings:SMA is a neurodegenerative disorder with autosomal recessive genetic heredity. It is caused by a homozygous deletion of the survival motor neuron (SMN 1 ) gene. This genetic alteration results in reduced levels of the SMN protein, leading to degeneration of alpha motor neurons of the spinal cord and resulting in muscle weakness and progressive symmetrical proximal paralysis. It is known that basic nutritional and respiratory care and physiotherapy can be important to delaying disease progression and prolonging patients' lives. Several drugs are being tested, some new, others, such as valproic acid, already known; paralysis can be halted, but not reversed. Conclusions:SMA is a difficult to diagnose disorder, because it is little known, and treatment is uncertain. Pharmacological treatments and supportive therapies are not yet able to recover motor neurons or muscle cells that have already been lost, but are aimed at delaying disease progression and improving patients' residual muscle function, as well as offering better quality of life and life expectancy.

show abstract

Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy

Cited by 99 publications

References 28 publications

Cardiotrophin-1 Review

Cardiotrophin-1 Review

Treatment strategies for spinal muscular atrophy

Atrofia muscular espinhal: diagnóstico, tratamento e perspectivas futuras

Contact Info

Product

Resources

About