Research

Table of Contents

• Will Research Impact My Child?
• Research Update
• RSRF-funded Study Suggests Rett Syndrome
  May Be Preventable
• Press Releases
• Glossary

Will Research Impact My Child?

Work in the lab of Rudolf Jaenisch in Boston has shown that RTT-like symptoms in a mouse model are preventable through genetic engineering. This is proof that RTT is likely treatable at birth. Your next logical question is “Can we reverse symptoms in children who already have Rett?”  Experiments, using animal models, are ongoing and we hope to bring you encouraging news soon. Rett Syndrome will eventually be treated in either of three ways: drug(s), gene therapy or a combination of both.

With regards to drugs either of two scenarios will take place 1) the realization that existing drugs meant for other disorders will also help RTT or 2) the development of new drugs specifically created to treat RTT. 

Discovering new drugs will involve having a better understanding of 1) what exactly does MECP2 do and 2) specifically where in the brain does it do it. This information will point to potential drug targets which will then need to be screened to identify compounds that will modulate the targets. Any resulting drug compounds will then need to be tested for safety and efficacy first in animal models and then in patients via clinical trials. 

Gene therapy has been around for a number of years and is beginning to have its first successes. The fundamentals of gene therapy involve inserting your gene of interest (MECP2 in our case) into the DNA of a harmless virus. The virus acts like a Trojan horse and delivers the inserted gene into the patient.

Delivering genes into the brain and ensuring those genes continue to be expressed is no easy matter. Years of research have already taken place and the techniques are not yet perfected. The good news is, however, that we will benefit from progress that has occurred in fields like Parkinson’s Disease.  RSRF is currently funding a Gene Therapy Collaboration to explore what types of viruses and delivery systems are most ideal for RTT. Promising results will lead to testing on animal models followed by clinical trials in humans.

There is a lot of work to be done. Fortunately there are many talented scientists focused on answering these questions and exciting breakthroughs are happening. No one is more motivated to find treatments and a cure for Rett than parents whose children are suffering. The trustees, staff and volunteers of RSRF fervently believe that the research we are funding today will impact our children and yours. Our research agenda is aggressive and focused. We will not stop until treatments and a cure are found.

As you read through the materials please feel free to contact Monica Coenraads, RSRF Director of Research,with any questions you might have. She can be reached via email at monica@rsrf.org or by phone at 203.445.9233.

RSRF FUNDED STUDY SUGGESTS RETT SYNDROME MAY BE PREVENTABLE

These experiments lay the groundwork for the next key project: determining whether Rett Syndrome is reversible and if so identifying the appropriate time frame for MeCP2 re-introduction - Dr. Rudolf Jaenisch

Dr. Rudolf Jaenisch of Whitehead Institute in Cambridge, MA published a paper in the April 6, 2004 online issue of the Proceedings of the National Academy of Sciences entitled “Expression of Mecp2 in postmitotic neurons rescues Rett syndrome in mice”.

The Rett Syndrome mice” were genetically engineered so that healthy Mecp2 protein would be introduced when the brain cells became mature (approx. at birth).  The genetically engineered mice were “rescued” from ever developing Rett-like symptoms.

From this, Dr. Jaenisch concludes:

• children born with Rett Syndrome probably have healthy neurons
• if treatments were available it is likely these newborns would never manifest the symptoms of Rett
• too much Mecp2, 4-6 fold, is harmful (important to know when treatments are being developed)

Dr. Jaenisch and others are currently attempting crucial experiments to determine whether the symptoms of full-blown Rett Syndrome can be improved or reversed by introducing healthy Mecp2 protein. If this proves possible then the search for treatment options can begin.

Dr. Jaenisch has received RSRF funds totaling $460,000 over the past 3 ½ years, including the recent G.E.A.R. award (Grants of Excellence to Accelerate Rett Research).  These funds have been used to create and characterize the mutant mice, understand when and where the Mecp2 protein is found in mice brains and determine when Mecp2 plays a critical role.

Current funding is aimed at determining if Rett is reversible. This is the type of serious, results-oriented research that RSRF funds.  The possibility of rapid progress towards treatments is within our reach. We need your support to continue driving the science forward. Glossary

alternative splicing
Different ways of combining a gene's exons to make variants of the complete protein.

amino acid
Any of a class of 20 molecules that combine to form proteins in living things.

cell
Small, watery, membrane-bound compartment filled with chemicals; the basic subunit of any living thing.

chromatin
That portion of the cell nucleus which contains all of the DNA of the nucleus in animal or plant cells.

chromosomes
Structures found in the nucleus of a cell, which contain the genes. Chromosomes come in pairs, and a normal human cell contains 46 chromosomes, 22 pairs of autosomes and two sex chromosomes.

coding regions
Those parts of the DNA that contain the information needed to form proteins.

codon
A set of three adjoined nucleotides (triplet) that codes for an amino acid or a termination signal.

de novo mutation
An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents or in the fertilized egg. itself

DNA
The substance of heredity; a large molecule that carries the genetic information that cells need to replicate and to produce proteins.

encode
To specify, after decoding by transcription and translation, the sequence of amino acids in a protein.

exons
The protein-coding DNA sequence of a gene.

frameshift mutation
An alteration of DNA where insertion or deletion of sequence occurs that is not a multiple of three base pairs, thus disrupting the gene/protein normal code.

genes
The fundamental physical and functional unit of heredity. A gene is an ordered sequence of nucleotides located in a particular position on a particular chromosome that encodes a specific functional product (i.e., a protein or RNA molecule).

gene expression
The process by which a gene's coded information is converted into the structures present and operating in the cell. Expressed genes include those that are transcribed into mRNA and then translated into protein and those that are transcribed into RNA but not translated into protein (e.g., transfer and ribosomal RNAs).

genotype
The genetic constitution of an organism, as distinguished from its physical appearance (its phenotype).

genome
All the genetic material in the chromosomes of a particular organism.

germline mosaicism
The presence of a gene mutation for a disease trait in some yet not all of an individual's sexual reproductive cells (germ cells) within the ovaries or testes (gonads).

heterozygous
The presence of different alleles at one or more loci on homologous chromosomes.

homozygous
An organism that has two identical alleles of a gene.

imprinting
A phenomenon in which the disease phenotype depends on which parent passed on the disease gene.

in vitro
Studies performed outside a living organism such as in a laboratory.

in vivo
Studies carried out in living organisms

introns
DNA sequence that interrupts the protein-coding sequence of a gene; an intron is transcribed into RNA but is cut out of the message before it is translated into protein.

Klinefelter Syndrome
A genetic abnormality that is caused by an extra X chromosome in a male, and is typically identified as 47, XXY.

knockout
Deactivation of specific genes; used in laboratory organisms to study gene function.

MECP2
The human gene located on the X chromosome that causes Rett Syndrome when it’s mutated

MeCP2
The protein encoded by the MECP2 gene.

Mecp2
The mouse gene comparable to the human MECP2 gene.

Mecp2
The mouse protein that is encoded by the mouse gene.

Methionine
An amino acid, one of the 20 building blocks of protein.

missense mutation
A mutation that changes a codon for one amino acid into a codon specifying another amino acid.

mutation
A change in the number, arrangement, or molecular sequence of a gene.

neurons
The nerve cells of the brain that carry out neurological function.

neurotransmitter
Specialized chemical messenger (eg, acetylcholine, dopamine, norepinephrine, serotonin) that sends a message from one nerve cell to another. Most neurotransmitters play different roles throughout the body, many of which are not yet known.

non-coding regions
DNA which does not contain instructions for making proteins. Some noncoding DNA is involved in regulating the activity of coding regions. The function of a large percentage of non coding regions is unknown.

nonsense mutation
A change in DNA that causes a (termination) codon to replace a codon representing an amino acid.

nucleotide bases
Subunit of DNA or RNA, consisting of one chemical base plus a phosphate molecule and a sugar molecule.

nucleus
The cellular organelle in eukaryotes that contains most of the genetic material.

phenotype
The physical characteristics of an organism or the presence of a disease that may or may not be genetic.

plasticity 
The ability of neural circuits to undergo changes in function or organization due to previous activity.

protein
Large, complex molecule composed of amino acids. Proteins are essential to the structure, function, and regulation of the body. Examples are hormones, enzymes, and antibodies.

RNA(Ribonucleic acid)
A chemical found in the nucleus and cytoplasm of cells; it plays an important role in protein synthesis and other chemical activities of the cell. The structure of RNA is similar to that of DNA. There are several classes of RNA molecules, including messenger RNA, transfer RNA, ribosomal RNA, and other small RNAs, each serving a different purpose.

somatic mosaicism
The occurrence of two different cell lines in a particular tissue or tissues which differ genetically.

synapse
The junction where a signal is transmitted from one nerve cell to another, usually by a neurotransmitter.

Threonine
A colorless crystalline amino acid found in protein.

transcription
The synthesis of an RNA copy from a sequence of DNA (a gene); the first step in gene expression.

transcription factor
A protein that binds to regulatory regions and helps control gene expression.

translation
The process in which the genetic code carried by mRNA directs the synthesis of proteins from amino acids.

X chromosome
One of the two sex chromosomes, X and Y.

X inactivation
The phenomenon in a female by which one X chromosome is randomly inactivated in an early embryonic cell, with fixed inactivation of that same X in all cells descended from that cell.

Y chromosome
One of the two sex chromosomes, X and Y.