Laboratory_Mice_Cured_of_Rett_Syndrome

There are no guarantees in life, just like there are no guarantees for every pregnancy to be a healthy one. Yet no one goes into a pregnancy fearing the worse either. For Bonnie Chaballa and her husband Steve, they had dreamed of one day having a very large family. They had a son in the fall of 1997 and a daughter in 1999. They were blessed once again in the summer of 2000 to find that they would be having another little girl the following year. Lily Hope was born on 26 March 2001, to not only proud parents but to two proud siblings. They quickly fell pregnant again when Lily Hope was just four months pregnant. They were thrilled as they wanted a big family. However their lives were changed when major complications erupted during birth and their son died shortly after. Testing would show that their son had Rett Syndrome; a disease that neither Bonnie nor Steve knew anything about (Bonnie, interview). They did not know that their lives would forever be altered again when Lily Hope turned two years old with be diagnosed with the same disorder that killed her brother. Rett Syndrome is a rare neurobiological disorder that affects roughly about one female out of 10,000 that are born (IRSF, 2008). This disorder was believed only to affect females as the research studies found that only a small number of males were affected (WIBS, 2009). Research has proven that the main cause of Rett Syndrome is linked to a change in a single gene. This gene, MeCP2, hinders nerve cell growth which causes the cells from forming spines which are used for nerve-cell-to-nerve-cell communication (WIBS, 2009). A female child born with Retts starts of their life like any other normal child, however they soon abruptly stop. In most cases, the young child losses skills and abilities (IRSF, 2008) such as movement, loss of speech, reduced head size, breathing and heart rhythm irregularities. There are four stages that are used to help characterize the disorder and improve its recognition and diagnosis (IRSF, 2008). Stage one can be called the early onset phase. It is in this phase, roughly before a baby is 6 months old, where the head circumference begins to slow is growth (Lindberg 2006). Most of the symptoms of this disease are easily overlooked as they are very subtle ones. Usually babies within this stage of Rett’s show a decrease in eye contact and become less interested in playing with their toys (IRSF, 2008). They also will show delays in their ability to sit unassisted and trying to crawl. When looking back at Lily Hope’s first 6 months, the signs were all there yet Bonnie and Steve did not see them as a concern. They had two older children and felt like most parents do when you say, “all kids are different and learn at a different level” (Bonnie, interview) As kids turn one through the age of four, children of Rett syndrome slowly begin to lose the ability to talk and the use of their hands. For Bonnie and Steve, this is the stage when they started to notice a difference in Lily Hope (Bonnie, interview). Like many other children with Retts, Lily Hope began wringing her hands together, or constantly clapping them. It was like Lily Hope had no control over what her body was doing. There were times when they found their little girl holding her breath and even purposely hyperventilating. “It was at that moment that we knew something was wrong with our little girl. Yes she was slow at learning things from our other children but this was more then that. And it would be that moment when our doctor told us that we needed to get a neurologist appointment that our worst fears had come true.” (Bonnie interview). Usually between the ages of 2, if you are lucky, through the age of 10, is what doctors call the third stage; a plateau stage. A child’s behavior will slowly improve however they still experience problems with mobility (RSRT, 2008). They will also cry less then other kids, they will not be as irritable, their alertness will improve as will their attention span and nonverbal communication skills increase slightly (RSRT, 2008). Sadly, not all children are lucky to stay in this stage. For those that sadly reach the last stage, stage four, and these children lose everything. Their mobility decline back to that of stage one or even goes away completely where they are bound by a wheelchair for life (RSRT, 2009). . They also experience muscle weakness and scoliosis which is an abnormal curvature of the spine. For those children who have worked so hard to relearn how to speak and use their hands has that taken away in this stage when all hand eye coordination is gradually decreased (RSRT, 2008). Most children of Rett syndrome can live well into their 40s and beyond help and care of an assisted life, however there are a few of some reports of sudden death while they are sleeping. Though there is no cure for Rett Syndrome there are many researches being performed at institutions and within charities to help understand the disorder better in hopes to find a cure (IRSF, 2008). The Wellcome Trust, is an independent charity funding research to improve human and animal health (RSRT, 2008). Their goal is to provide funding to thousands of universities and other academic centers all over the country in hoping to help research benefit our current and future generations. One of the researches that the Wellcome Trust provided funding for was to Adrian Bird and his colleagues at Edinburgh University and the University of Glasgow (RSRT, 2008). . Their research was to show that in mice reactivating a key gene could reverse the symptoms of Rett Syndrome. Dr. Stuart Cobb is a Neuroscientist from the University of Glasgow's Faculty of Biomedical and Life Sciences. His work consists of research of the basic mechanisms of synaptic transmission, patterned hippocampal network activity and synaptic plasticity and modulation of epileptiform activity (IRSF, 2008). For his expertise in the neuroscience department he was asked to work along side Adrian Bird with the MeCP2 gene reversal research. In regards to this breakthrough Rett Syndrome research he stated, "This breakthrough provides a small piece of hope for sufferers.” (IRSF, 2008) Adrian Bird, Ph.D became a Buchanan Professor of Genetics at Edinburgh in 1990 and then went on in 1999 to create the Wellcome Trust Centre for Cell biology and later that same year become director. His achievements have included President of the Scientific Committee of Rett Syndrome Research Foundation and UK Breakthrough Breast Cancer; as well as a Trustee of the Trust Kirkhouse (RSRT, 2008). He has also worked on the editorial board of Molecular and Cellular Biology and Molecular Cell. Howard Hughes International Fellowship, the Gabor Medal of the Royal Society and the Louis-Jeantet Prize for Medicine are all high honors and awards that Adrian Bird has received throughout his life. And on top of all these honors he is also a Fellow of the Royal Societies of London and Edinburgh and the 'Academy of Medical Sciences (RSRT, 2009). It was through television programs with showed scientists explaining science that got Adrian Bird interested in science because they showed him that there was something interesting out there (RSRT, 2008). . He devoured himself in reading biology books which is where his interest in DNA began. But it wasn’t until his undergraduate time that he found himself at research as a future field. His first laboratory experience was working on a study of isolated genes. From there other work included with ribosomal RNA genes (rDNA) and DNA methylation (RSRT, 2008). Adrian Bird is one of the leading specialists in the gene, MeCP2 which he discovered in 1989 (RSRT, 2008). This gene works like a switch, turning other genes on and off. With his team consisting of research assistant Jacky Guy, Jian Gan, Jim Selfridge, Dr Stuart Cobb, they used adult mice infected with RS to show that if they targeted the bad gene, they could reverse the affects of RS. The research team created a breed of mice whose MeCP2 gene was inactive by the insertion of an extra block of DNA (IRSF, 2008). At just a few weeks old, the mice started to develop symptoms of Rett syndrome that was also seen in children. The team, upon studying of these mice, inserted a second gene that cut out the interfering block of DNA in MeCP2 (RSRT, 2008). This second gene could be activated only when the drug tamoxifen was administered (RSRT, 2008). Tamoxifen is a drug used to block the actions of the female hormone, estrogen. The mice that were given the medication tamoxifen were the only time when they showed a decline in the symptoms associated with Retts (RSRT, 2008). The team believed that once MeCP2 does not partake in the steps that lead neurons to grow and make the right connections, is what causes the symptoms of Retts to decline. The gene only comes into play after in maintaining the genetic decisions the neutrons have made (RSRT 2008). Through their experiment they were able to demonstrate that a neurological disease such as Rett Syndrome can be corrected by restoring the missing component of cells (RSRT 2008). However this is only a fix not a cure. Research is still being conducted for a cure. Adrian Bird once said, “Like many other people, we expected that giving MECP2 to mice that were already sick would not work. The ideas that you could put back an essential component after the damage to the brain is done and recover an apparently normal mouse seemed farfetched, as nerve cells that developed in the absence of a key component were assumed to be irrevocably damaged. The results are gratifyingly clear, though, and must give hope to those who are affected by this distressing disorder (IRSF, 2008).” Their breakthrough means so much too so many little girls living with RS who have lost so much. With this study researchers can study the specific genes and try to understand the different types of mutations and how it affects Rett Syndrome (RSRT 2008). There is still a long way to go with finding treatments and a cure for children of Rett Syndrome. Scientists are able to erase symptoms of the disorder in mice however they are still baffled when it comes to taking their experiment to human patients (RSRT 2008). Just the idea of getting some mobility, hand eye coordination and the possibility of speech back provides hope to everyone. Bonnie and Steve spend a lot of their time researching and speaking out on Rett Syndrome. Their 8 year old daughter Lily Hope maybe a “silent angel” as most Rett Syndrome kids are called but she is a strong willed girl who doesn’t take “you can’t do this cause of your disability” as an answer (Bonnie Interview). Many people wouldn’t know what Rett Syndrome was if it were not for scientists like Adrian Bird or Dr. Stuart Cobb and many other researchers. They have continued the quest to find a treatment for children with Rett Syndrome with one paper entitled Funded Research Links Rett Syndrome to Mitochondrial Gene published on the Rett Syndrome Research Foundation website, (RSRT, 2009) depicts further findings of what might be causing the disorder in hoping to find a treatment. It is through these researches that discoveries in science are unexpected and that breakthroughs in one area turn out to have unexpected benefits in other unrelated disciplines (RSRT, 2008). For example if we look at Adrian Bird’s research in the reversal of Rett Syndrome no one would have provided the means to help support his research if it was not for the findings from Huda Zoghbi who in 1999 discovered that Rett Syndrome was indeed actually caused by mutations in MeCP2 genes (RSRT, 2008). To fully comprehend social and culture we have to first understand and be able to apply research methods used in science. By using these research methods correctly, we will find the answers that are valid and reliable or ones that will accurately relate to the issues being questioned. Science is not everywhere but the process by which we actually find these things out. By developing new methods we can overturn mistaken assumptions. In order for use to understand Rett syndrome we must understand what causes it. Understanding and educating ourselves and being aware of the many effects that can happen to our bodies when and if we are born with a your body if your are born with one single abnormal gene (Lindberg 2006). These breakthroughs provide us with some unanswered questions and helps give us information that as parents we can test on your children that doctors may miss (Lindberg 2006). Hopes to find a cure one day is on the minds of all scientists that have helped in the researches of Rett Syndrome. We are further along today with knowing the causes and possible fixes then we did 30 years ago. There is a cure out there and through the advance technology that continues to grown in society, someone out there is going to find it. Reference: (2007). The Jackson Laboratory. Retrieved 13 Nov 2009 from http://jaxmice.jax.org/ (2008). International Rett Syndrome Foundation (IRSF). Retrieved 13 Nov 2009 from http://www.rettsyndrome.org (2008) Rett Syndrome Research Trust Blog (RSRT) . Retrieved 29 Nov 2009 from http://www.rsrt.org/ Erickson, M., (2005) Science, Culture and Society: Understanding science in the 21st century Guy, Jacky, Jian Gan, Jim Selfridge, Stuart Cobb, and Adrian Bird. "Reversal of neurological defects in a mouse model of Rett syndrome." Science Express 315.5815 (2007): 1143–1147. http://www.sciencemag org/cgi/content/abstract/315/5815/. Web. 24 Nov. 2009. Lewis, J. and D. Wilson (1998). Pathways to Learning in Rett Syndrome . London: David Fulton Publishers Ltd. Chaballa, Bonnie. Personal interview. 28 Nov. 2009 Lindberg, Barbro (2006). Understanding Rett Syndrome: A Practical Guide for Parents, Teachers, And Therapists. Ontario: Hogrefe & Huber Publishing Whitehead Institute for Biomedical Research (WIBS) (2009, February 10). Possible Treatment For Neurological Disorder Rett Syndrome -- Most Common Basis Of Autism In Girls. ScienceDaily. Retrieved November 24, 2009, from http://www.sciencedaily.com­ /releases/2009/02/090209205047.htm