MECP2 Duplication Sydrome (M2DS) is a rare X-linked genetic disorder that causes the over expression of MECP2 protein. It largely affects young male individuals.
Contents
- MECP2 Duplication Syndrome Reversal in Mice
- The 401 Project
- The Rett Syndrome Research Trust MECP2 Duplication Syndrome Fund
- References
The primary symptoms of M2DS include infantile hypotonia, delayed psychomotor development, impaired speech, abnormal or absent gait, epilepsy, spasticity, gastrointestinal motility problems, recurrent infections, and early death. Signs of this disorder are confused with those of autism spectrum disorders and cerebral palsy. The incidence of M2DS is currently unknown but thought to represent ~1% of X-linked male mental disability cases.
Recent technological breakthroughs in communication have shown that children affected by MECP2 Duplication Syndrome understand language but cannot speak. In the very recent past, a combination of non-existent or limited speech with poor motor skills had caused these adolescent individuals to present with the cognitive abilities of an infant. Pioneering communication work with MECP2 Duplication Syndrome children and assistive technology (eye gaze communication) devices have demonstrated that these children have the ability to communicate requests and feelings.
The genetic abnormality that causes MECP2 duplication syndrome is a double dose or duplication of the MECP2 or Methyl CpG binding protein 2 gene. The MECP2 protein plays a pivotal role in regulating brain function. Too little or too much of the MECP2 protein results in brain dysfunction and physical impairment. Mutations in the MECP2 gene are also commonly associated with Rett syndrome in females.
Advances in genetic testing and more widespread use of Array CGH (Comparative Genomic Hybridization) has led to increased diagnosis of MECP2 duplication syndrome. Array CGH allows for sub-microscopic (cannot be seen under a microscope) detection of missing or additional copies of genetic material and is the best screening test for a child with developmental delay as it will detect a number of genetic disorders including MECP2 duplication syndrome.
Research into MECP2 duplication syndrome is in its infancy, which means we also do not know the spectrum (mildness to severity). Preliminary studies suggest that prevalence may be 1.8 per 10,000 live male births. 50% of cases do not live beyond 25 years of age.
MECP2 Duplication Syndrome Reversal in Mice
In a Nature article published on November 25, 2015, it was revealed that researchers at the Baylor College of Medicine, led by Dr. Huda Y. Zoghbi, have reversed MECP2 Duplication Syndrome in adult symptomatic mice using antisense oligonucleotide (ASO) therapy. In this landmark letter to Nature, mice treated with an experimental ASO administered through the central nervous system experienced the reduction of MECP2 protein to normal levels. Many impressive results were observed. Several behavioral tests were conducted, and in all cases, symptoms of hypoactivity, anxiety, and abnormal social behavior were resolved. Additionally, the seizure activity of the mice and abnormal EEG discharges were abolished. Lastly, initial studies demonstrated that reducing the MECP2 protein levels to the correct amount also normalized the expression of the other genes controlled by the MECP2 protein. Excitingly, the ASO was also administered to lymphoblastoid cells from MECP2 Duplication Syndrome patients, and MECP2 mRNA levels were restored to the correct concentration in these cells.
This groundbreaking research shows that ASO gene therapy is a promising approach to treat MECP2 Duplication Syndrome. Further scientific studies need to be conducted before this therapeutic approach can be tested on humans, but this study is the first hurdle cleared of the many inherent to the drug development process. This research was funded by donations to the Rett Syndrome Research Trust MECP2 Duplication Fund by the friends and families of children affected by MECP2 Duplication Syndrome
The 401 Project
The 401 Project was established in 2012 to raise funds to cure MECP2 Duplication Syndrome. In 2012, a concerted parent-driven effort was established to raise funds for the initial MECP2 reversal experiments conducted at the Baylor College of Medicine. Each MECP2 family pledged to raise $401.00 in funds to cover the research program cost. The initiative was a success, and the 401 Project was born. The 401 Project name was maintained as it is fundamental to the philosophy: the collection of individual efforts produces high impact results. The 401 Project was established by parents of children affected by MECP2 Duplication Syndrome. Today, the 401 Project is maintained by a group of parent facilitators who guide fundraising programs, scientist interactions, research finding translations, and social media activities. There are very minimal direct costs associated with running the 401 Project, and these costs are covered by the parent facilitators. Every penny donated to the 401 Project goes to research.
The Rett Syndrome Research Trust MECP2 Duplication Syndrome Fund
All funds raised through the 401 Project initiative are directly deposited into the Rett Syndrome Research Trust MECP2 Duplication Syndrome Fund. The Rett Syndrome Research Trust (RSRT) is a registered non-profit organization, and all donations are fully tax deductible.
Both Rett Syndrome and MECP2 Duplication Syndrome are caused by mutations in the MECP2 gene. Rett Syndrome-affected individuals do not produce enough MECP2 protein in their brains while MECP2 Duplication-affected individuals produce far too much MECP2 protein. Research conducted on the earlier-discovered Rett Syndrome was easily leveraged to initiate promising research to cure MECP2 Duplication Syndrome.
RSRT was founded in 2008 by Monica Coenraads. Since 1999, Monica has led the surge in research for genetic disorders caused by mutations in the MECP2 gene. The MECP2 Duplication community is beyond fortunate that Monica has championed MECP2 Duplication Syndrome research under the RSRT umbrella. Under Monica's leadership, over $40,000,000 has been raised for research on MECP2-associated genetic disorders. RSRT operates by constantly engaging academic scientists, clinicians, industry, investors, and affected families. These relationships catalyze the development and execution of a research agenda that neither academia nor industry could achieve alone. RSRT identifies, solicits, evaluates, prioritizes, funds and monitors ambitious research projects that have the greatest likelihood of impacting the lives of those afflicted with Rett Syndrome and MECP2 Duplication Syndrome.