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AAV9-mediated SH3TC...
AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C
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Georgiou, E. (författare)
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Kagiava, A. (författare)
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Sargiannidou, I. (författare)
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Schiza, N. (författare)
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Stavrou, M. (författare)
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Richter, J. (författare)
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Tryfonos, C. (författare)
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- Zetterberg, Henrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Heslegrave, A. (författare)
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Christodoulou, C. (författare)
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Kleopa, K. A. (författare)
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Molecular Therapy. - 1525-0016. ; 31:11, s. 3290-3307
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Type 4C Charcot-Marie-Tooth (CMT4C) demyelinating neuropathy is caused by autosomal recessive SH3TC2 gene mutations. SH3TC2 is highly expressed in myelinating Schwann cells. CMT4C is a childhood-onset progressive disease without effective treatment. Here, we generated a gene therapy for CMT4C mediated by an adeno-associated viral 9 vector (AAV9) to deliver the human SH3TC2 gene in the Sh3tc2-/mouse model of CMT4C. We used a minimal fragment of the myelin protein zero (Mpz) promoter (miniMpz), which was cloned and validated to achieve Schwann cell-targeted expression of SH3TC2. Following the demonstration of AAV9miniMpz.SH3TC2myc vector efficacy to re-establish SH3TC2 expression in the peripheral nervous system, we performed an early as well as a delayed treatment trial in Sh3tc2-/mice. We demonstrate both after early as well as following late treatment improvements in multiple motor performance tests and nerve conduction velocities. Moreover, treatment led to normalization of the organization of the nodes of Ranvier, which is typically deficient in CMT4C patients and bers, increased myelin thickness and reduced g-ratios at both time points of intervention. Taken together, our results provide a proof of concept for an effective and potentially translatable gene replacement therapy for CMT4C treatment.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- marie-tooth-disease
- nervous-system disease
- in-vitro
- protein
- model
- delivery
- mutations
- expression
- vectors
- aav
- Biotechnology & Applied Microbiology
- Genetics & Heredity
- Experimental Medicine
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Georgiou, E.
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Kagiava, A.
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Sargiannidou, I.
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Schiza, N.
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Stavrou, M.
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Richter, J.
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visa fler...
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Tryfonos, C.
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Zetterberg, Henr ...
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Heslegrave, A.
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Christodoulou, C ...
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Kleopa, K. A.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
- Artiklar i publikationen
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Molecular Therap ...
- Av lärosätet
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Göteborgs universitet