Progress in understanding Friedreich's ataxia using human induced pluripotent stem cells

Expert Opinion on Orphan Drugs
Anna M SchreiberMarek Napierala

Abstract

Friedreich's ataxia (FRDA) is an autosomal recessive multisystem disease mainly affecting the peripheral and central nervous systems, and heart. FRDA is caused by a GAA repeat expansion in the first intron of the frataxin (FXN) gene, that leads to reduced expression of FXN mRNA and frataxin protein. Neuronal and cardiac cells are primary targets of frataxin deficiency and generating models via differentiation of induced pluripotent stem cells (iPSCs) into these cell types is essential for progress towards developing therapies for FRDA. This review is focused on modeling FRDA using human iPSCs and various iPSC-differentiated cell types. We emphasized the importance of patient and corrected isogenic cell line pairs to minimize effects caused by biological variability between individuals. The versatility of iPSC-derived cellular models of FRDA is advantageous for developing new therapeutic strategies, and rigorous testing in such models will be critical for approval of the first treatment for FRDA. Creating a well-characterized and diverse set of iPSC lines, including appropriate isogenic controls, will facilitate achieving this goal. Also, improvement of differentiation protocols, especially towards proprioceptive sensory neurons...Continue Reading

References

Oct 17, 1996·The New England Journal of Medicine·A DürrM Koenig
Feb 20, 2002·FEBS Letters·Carlos J MirandaMassimo Pandolfo
Dec 5, 2003·Seminars in Pediatric Neurology·Massimo Pandolfo
Jun 18, 2004·Journal of Neurology, Neurosurgery, and Psychiatry·L PianeseS Cocozza
Jul 6, 2004·Genomics·Sahar Al-MahdawiMark Pook
Aug 22, 2006·Nature Chemical Biology·David HermanJoel M Gottesfeld
Aug 25, 2006·Nature·Irina KlimanskayaRobert Lanza
Jun 29, 2007·Human Molecular Genetics·Alain MartelliHélène Puccio
Nov 22, 2007·Science·Junying YuJames A Thomson
Jan 24, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Robert D Wells
Oct 22, 2008·Brain : a Journal of Neurology·Filippo FortunaValerio Carelli
Apr 11, 2009·Journal of Neurology·Massimo Pandolfo
Apr 11, 2009·Journal of Neurology·Massimo Pandolfo, Annalisa Pastore
Apr 11, 2009·Journal of Neurology·Hélène Puccio
Jun 23, 2009·Trends in Genetics : TIG·Vincent Dion, John H Wilson
Oct 31, 2009·PLoS Genetics·Scott DitchEd Grabczyk
Nov 7, 2009·Audiology & Neuro-otology·Gary RanceMartin B Delatycki
Feb 15, 2011·Journal of the Neurological Sciences·Arnulf H Koeppen
May 10, 2011·Brain Research Reviews·Daniele Marmolino
Jul 4, 2012·Journal of Child Neurology·Martin B Delatycki, Louise A Corben
Jul 6, 2012·Journal of Child Neurology·R Mark Payne, Gregory R Wagner
Jul 13, 2012·The Journal of Biological Chemistry·Anasheh HalabiEd Grabczyk
Jul 27, 2012·Journal of Child Neurology·David R LynchGihan Tennekoon
Aug 17, 2012·Expert Review of Cardiovascular Therapy·David R LynchMartin G St John Sutton
Dec 26, 2012·Journal of the American Chemical Society·Florent ColinSandrine Ollagnier de Choudens
Apr 3, 2013·Methods in Molecular Biology·Nasir Malik, Mahendra S Rao
May 15, 2013·Trends in Biotechnology·Thomas GajCarlos F Barbas
Jul 24, 2013·Journal of Neurochemistry·Morgane PerdominiMark A Pook
Dec 10, 2013·Cell Stem Cell·Justine D MillerLorenz Studer
Dec 12, 2013·Pflügers Archiv : European journal of physiology·Yee-Ki LeeChung-Wah Siu
Apr 3, 2014·Nature Reviews. Genetics·Hyongbum Kim, Jin-Soo Kim
Apr 17, 2014·The Journal of Biological Chemistry·Yogesh K ChutakeSanjay I Bidichandani

❮ Previous
Next ❯

Citations

Jul 25, 2021·International Journal of Molecular Sciences·Cameron L McKnightAnn E Frazier

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Cardiac Organoids

Cardiac organoids are 3D organ-like structures that can be derived from patients with cardiovascular diseases and are important disease models for drug discovery. Discover the latest research on Cardiac Organoids here.

Cell Fate Conversion By mRNA

mRNA-based technology is being studied as a potential technology that could be used to reprogram cell fate. This technique provides the potential to generate safe reprogrammed cells that can be used for clinical applications. Here is the latest research on cell fate conversion by mRNA.

3D Cellular Models of Brain and Neurodegeneration

Brain organoids are three-dimensional in vitro cellular models of the brain that can recapitulate many processes such as the neurodevelopment. In addition, these organoids can be combined with other cell types, such as neurons and astrocytes to study their interactions in assembloids. Disease processes can also be modeled by induced pluripotent stem cell-derived organoids and assembloids from patients with neurodegenerative disorders. Discover the latest research on the models here.

Brain Organoids in Disease Modeling

Brain organoids are three-dimensional cell culture models derived from human pluripotent stem cells. Since they resemble the embryonic brain, they can be used to help study brain biology, early brain development, and brain diseases. Discover the latest research on brain organoids in disease modeling here.