Create a free QxMD account to receive personalized paper recommendations, relevant to your practice.

JOURNAL ARTICLE

In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate

Lars Brichta, Irmgard Holker, Karsten Haug, Thomas Klockgether, Brunhilde Wirth

Annals of Neurology 2006, 59 (6): 970-5

OBJECTIVE: Spinal muscular atrophy results from loss of the survival motor neuron 1 (SMN1) gene and malfunction of the remaining SMN2. We investigated whether valproic acid can elevate human SMN expression in vivo.

METHODS: Blood was collected from 10 spinal muscular atrophy carriers and 20 spinal muscular atrophy patients treated with valproic acid.

RESULTS: Seven of 10 carriers demonstrated increased SMN messenger RNA and protein levels. SMN2 messenger RNA levels were elevated in 7 patients and unchanged or decreased in 13 patients.

INTERPRETATION: We provide first proof of the in vivo activation of a causative gene by valproic acid in an inherited disease and discuss strategies of monitoring drug response in patients.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

SMN transcript stability: could modulation of messenger RNA degradation provide a novel therapy for spinal muscular atrophy? Christopher R Heier, Rocky G Gogliotti, Christine J DiDonato Journal of Child Neurology 2007, 22 (8): 1013-8

Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy. John Thurmond, Matthew E R Butchbach, Marty Palomo, Brian Pease, Munagala Rao, Louis Bedell, Monica Keyvan, Grace Pai, Rama Mishra, Magnus Haraldsson, Thorkell Andresson, Gisli Bragason, Margret Thosteinsdottir, Jon Mar Bjornsson, Daniel D Coovert, Arthur H M Burghes, Mark E Gurney, Jasbir Singh Journal of Medicinal Chemistry 2008 February 14, 51 (3): 449-69

Spinal muscular atrophy: from gene to therapy. Brunhilde Wirth, Lars Brichta, Eric Hahnen Seminars in Pediatric Neurology 2006, 13 (2): 121-31

Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells. Susanna M Grzeschik, Madhuri Ganta, Thomas W Prior, William D Heavlin, Ching H Wang Annals of Neurology 2005, 58 (2): 194-202

A sensitive assay for measuring SMN mRNA levels in peripheral blood and in muscle samples of patients affected with spinal muscular atrophy. Myriam Vezain, Pascale Saugier-Veber, Judith Melki, Annick Toutain, Eric Bieth, Marie Husson, Jean-Michel Pedespan, Louis Viollet, Isabelle Pénisson-Besnier, Séverine Fehrenbach, Jacqueline Bou, Thierry Frébourg, Mario Tosi European Journal of Human Genetics: EJHG 2007, 15 (10): 1054-62

SMN genotypes producing less SMN protein increase susceptibility to and severity of sporadic ALS. J H Veldink, S Kalmijn, A H Van der Hout, H H Lemmink, G J Groeneveld, C Lummen, H Scheffer, J H J Wokke, L H Van den Berg Neurology 2005 September 27, 65 (6): 820-5

Diverse small-molecule modulators of SMN expression found by high-throughput compound screening: early leads towards a therapeutic for spinal muscular atrophy. Jill Jarecki, Xiaocun Chen, Alexandra Bernardino, Daniel D Coovert, Michael Whitney, Arthur Burghes, Jeffrey Stack, Brian A Pollok Human Molecular Genetics 2005 July 15, 14 (14): 2003-18

Salbutamol increases SMN mRNA and protein levels in spinal muscular atrophy cells. C Angelozzi, F Borgo, F D Tiziano, A Martella, G Neri, C Brahe Journal of Medical Genetics 2008, 45 (1): 29-31

Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. L Brichta, Y Hofmann, E Hahnen, F A Siebzehnrubl, H Raschke, I Blumcke, I Y Eyupoglu, B Wirth Human Molecular Genetics 2003 October 1, 12 (19): 2481-9

Spinal muscular atrophy and therapeutic prospects. Brunhilde Wirth, Lars Brichta, Eric Hahnen Progress in Molecular and Subcellular Biology 2006, 44: 109-32

Make the most of Read.
Download the mobile app.

Want full text access to this paper?

Use Read by QxMD to access full text via your institution or open access sources.

Read also provides personalized recommendations to keep you up to date in your field.

Existing User

New to Read

In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate

Discussion

Related Papers

Want full text access to this paper?

Save your favorite articles in one place with a free QxMD account.

Read

Search Tips