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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2018

Open Access 01-12-2018 | Position statement

A perspective on “cure” for Rett syndrome

Authors: Angus John Clarke, Ana Paula Abdala Sheikh

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

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Abstract

The reversal of the Rett syndrome disease process in the Mecp2 mouse model of Guy et al. (2007) has motivated families and researchers to work on this condition. The reversibility in adult mice suggests that there is potentially much to be gained from rational treatments applied to patients of any age. However, it may be difficult to strike the right balance between enthusiasm on the one hand and realism on the other. One effect of this has been a fragmentation of the “Rett syndrome community” with some groups giving priority to work aimed at a cure while fewer resources are devoted to medical or therapy-based interventions to enhance the quality of life of affected patients or provide support for their families.
Several possible therapeutic approaches are under development that, it is claimed and hoped, may lead to a “cure” for patients with Rett syndrome. While all have a rationale, there are potential obstacles to each being both safe and effective. Furthermore, any strategy that succeeded in restoring normal levels of MECP2 gene expression throughout the brain carries potential pitfalls, so that it will be of crucial importance to introduce any clinical trials of such therapies with great care.
Expectations of families for a radical, rational treatment should not be inflated beyond a cautious optimism. This is particularly because affected patients with us now may not be able to reap the full benefits of a “cure”. Thus, interventions aimed at enhancing the quality of life of affected patients should not be forgone and their importance should not be minimised.
Glossary
Cas9
short for CRISPR associated protein 9. A genetic engineering tool used to cut a specific DNA sequence. It is usually associated with a CRISPR sequence.
CRISPR
abbreviation for Clustered Regularly Interspaced Short Palindromic Repeats. A genetic engineering tool used to locate a specific DNA sequence.
De novo mutations
a genetic alteration that is present for the first time in one family member because of a mutation in a germ line cell of one of the parents, or that arises in the fertilized egg itself during early development.
DNA
Deoxyribonucleic acid, the molecule that stores the material of heredity in cells within the body and and transmits it to future generations.
et al.
and the others
Genome
the complete set of genes or genetic material present in an organism
Germ line
cells that during reproduction pass on their genetic material to the offspring. These include the gametes, sperm and egg, and the cells from which they were produced.
MECP2 (italicised)
the gene that encodes methyl-CpG-binding protein 2 (MECP2). Mutations in this gene cause Rett syndrome.
MECP2 (non-italicised)
a protein that controls the expression of other genes. This protein appears to be essential for the normal function of brain cells.
MECP2 (all letters in capitals)
is the version of the gene or protein in humans, Mecp2 (only the first letter in capitala) is the version in the mouse.
RNA
Ribonucleic acid, a material related to DNA. It has multiple roles in the cell, especially in the synthesis of proteins. This includes acting as a messenger molecule that conveys the information in DNA from the cell nucleus into the cytoplasm so that it can be translated into protein.
X chromosome
a sex chromosome, two of which are normally present in female cells (designated XX) and only one in male cells (designated XY).
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Metadata
Title
A perspective on “cure” for Rett syndrome
Authors
Angus John Clarke
Ana Paula Abdala Sheikh
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-018-0786-6

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