Restoration of fatty aldehyde dehydrogenase deficiency in Sjögren-Larsson syndrome

Gene Therapy
Stefanie Haug, Markus Braun-Falco

Abstract

Sjögren-Larsson syndrome (SLS) is an autosomal recessive neurocutaneous disorder caused by mutation in the ALDH3A2 gene that codes for human fatty aldehyde dehydrogenase (FALDH). Sjögren-Larsson syndrome patients lack FALDH, which catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. The impaired FALDH activity leads to congenital ichthyosis, mental retardation and spasticity. The current lack of treatment is an impetus to develop gene therapy strategies by introducing functional FALDH into defective cells. We delivered human FALDH into keratinocytes of SLS patients using recombinant adeno-associated virus-2 vectors. Transduction of SLS keratinocytes resulted in an augmentation of FALDH activity comparable to phenotypically normal heterozygous carriers. Toxicity of long-chain aldehydes for FALDH-deficient cells decreased almost to the level of unaffected keratinocytes. Three-dimensional culture of corrected SLS keratinocytes revealed an ameliorated FALDH expression. These studies demonstrate the restoration of FALDH in human SLS cells supporting the concept of gene therapy as a potential future treatment option for SLS.

References

Jan 1, 1992·Journal of Inherited Metabolic Disease·T L KelsonW B Rizzo
Aug 18, 1999·Dermatology : International Journal for Clinical and Investigative Dermatology·B TaubeA Taïeb
Nov 21, 2000·Human Gene Therapy·F M Watt
Jan 25, 2002·European Journal of Pediatrics·M A WillemsenJ J Rotteveel
Nov 12, 2002·Cells, Tissues, Organs·Rikke ChristensenThomas G Jensen
Mar 17, 2004·Journal of Geriatric Psychiatry and Neurology·Joseph H FriedmanMartha M Trieschmann

❮ Previous
Next ❯

Citations

Apr 7, 2007·Topics in Magnetic Resonance Imaging : TMRI·Gilles LyonEdwin H Kolodny
Aug 22, 2006·Pediatric Dermatology·Kara A Mensink, Jennifer L Hand
Nov 18, 2009·Cases Journal·Farid Rezaei MoghaddamFatemeh Dehghani Zade
Jul 27, 2012·Journal of Inherited Metabolic Disease·Joris FuijkschotMichèl A A P Willemsen
Jul 10, 2008·Expert Opinion on Drug Metabolism & Toxicology·Satori A MarchittiVasilis Vasiliou
Jan 22, 2011·Journal of Dermatological Science·Daniela RoedlMarkus Braun-Falco
Nov 6, 2009·Environment International·Cathrine ThomsenMerete Eggesbø
Dec 17, 2009·Annales de dermatologie et de vénéréologie·C Chiavérini, UNKNOWN la Société française de dermatologie pédiatrique
Aug 23, 2016·Expert Opinion on Orphan Drugs·William B Rizzo
Mar 18, 2008·Experimental Dermatology·Masashi Akiyama, Hiroshi Shimizu
Apr 23, 2010·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Wolfgang Pfützner
Feb 5, 2009·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Markus KrugMark Berneburg
Feb 2, 2018·Nihon eiseigaku zasshi. Japanese journal of hygiene·Akiko Matsumoto
Sep 13, 2019·Ophthalmic Genetics·Samiksha Fouzdar-JainWilliam B Rizzo
Mar 17, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·David L EbenezerViswanathan Natarajan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

AAV-based Gene Therapy

Adeno-associated virus (AAV)-based gene therapy is a biological vector that is being researched to be used as a potential therapeutic option. This gene therapy is designed to insert fragments of DNA into targeted cells to help treat diseases, such as hemophilia a. Discover the latest research on AAV-based gene therapy here.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.