How to help girls with Rett syndrome, and strike a blow against extremism!

Today we have a guest post by Dr Nicoletta Landsberger, Associate Professor at the University of Insubria and Principle Investigator at the San Raffaele Rett Research Center. The San Raffaele Rett Research Center is supported by the Pro Rett Ricerce (proRett), a small but energetic Italian patient organization that funds research in Italy and abroad to find a cure for the neurodevelopmental disorder Rett syndrome, which affects about 1 in 10,000 girls. 

A fortnight ago Dr Landsberger was forced to cancel a fundraising event – which included a raffle – for proRett due to the threat of disruption from animal rights extremists. Our friends in Pro-Test Italia wrote an open letter to Italian prime minister Matteo Renzi about this attack on medical progress, and bought 200 tickets for the raffle (worth 400 Euros).

Regular readers of this blog will be well aware of the recent increase in animal rights extremism in Italy, but the campaign against a charity that seeks to find effective therapies for a disease that devastates many thousands young lives around the world marks a new low. We need to support our friends in Italy, to support the children who suffer from Rett syndrome, and to send a strong message to animal rights extremists that their intimidation and bullying will not be tolerated. We are not asking you to march in the streets, or to sign a petition, or even to write a letter, we are asking you to do something a lot simpler; we are asking you to make a donation to proRett.

Please take a few minutes to give proRett what you can via their PayPal account, even a small donation will help (The PayPal account is in Italian, but essentially identical to the English language version. United States is Stati Unita in Italian, and United Kingdom is Regno Unito. If you are unsure of anything just use Google Translate).

Imagine Anna, a wonderful eight months girl sitting in her high chair and turning the pages of a book while watching it. Imagine Anna’s mother showing you other pictures of her daughter, smiling to her siblings or grasping objects. Everything seems normal, but then, few months later, the pictures are different. Anna is not smiling anymore, the expression of her face is different, the brightness has disappeared and in many pictures Anna has protruding jaws. Anna’s mother tells me “this is when I realized that something was changing…. At that time Anna’s progress stopped, the ability to hold the book and turn its pages was lost, overcome by continuous stereotyped hand-wringing movements. Rett syndrome and its regression phase were taking Anna away, locking her in her body for good”.

Anna is now 16, she is wheel chair bound, unable to talk and to play; like most girls affected by Rett syndrome she suffers from seizures, hypotonia, constipation, scoliosis, osteopenia, and breathing irregularities. Like most girls affected (over 90%) by typical Rett syndrome she carries a mutation in the X-linked MECP2 gene.

Today, almost 30 years after Rett syndrome was internationally recognized as a unique disorder mainly affecting girls, we know that it is a rare genetic disease, and that because of its prevalence (roughly 1:10.000 born girls) can be considered one of the most frequent causes of intellectual disability in females worldwide.

Rett syndrome is a pediatric neurological disorder with a delayed onset of symptoms and has to be clinically diagnosed relying on specific criteria. Girls affected by typical Rett Syndrome are born apparently healthy after a normal pregnancy and uneventful delivery and appear to develop normally usually throughout the first 6-18 months of life. Then their neurological development appears to arrest and, as the syndrome progresses, a regression phase occurs that leads to a documented loss of early acquired developmental skills, such as purposeful hand use, learned single words/babble and motor skills. During the regression phase, patients develop gait abnormalities and almost continuous stereotypic hand wringing, washing, clapping, and mouthing movements that constitute the hallmark of the disease. Many other severe clinical features are associated with typical Rett syndrome, including breathing abnormalities, seizures, hypotonia and weak posture, scoliosis, weight loss, bruxism, underdeveloped feet, severe constipation and cardiac abnormalities. Rett syndrome patients often live into adulthood, even though a slight increase in the mortality rate is observed, which is often caused by sudden deaths, probably triggered by breathing dysfunctions and cardiac alterations. There are no effective therapies available to slow or stop the disease, only treatments to help manage symptoms.

Genetic analyses show that most cases are caused by a mutation in the X-linked MECP2 gene, and many different missense mutations and deletions have been identified within the MECP2 gene of girls with Rett syndrome that prevent the protein from functioning correctly. The formal genetic proof of the involvement of the MECP2 gene in Rett syndrome is further provided by a number of diverse mouse models carrying different MECP2 alterations, which display the same symptoms observed in human patients (for more information see this recent open-access review by David Katz and colleagues) . These animals that fully recapitulate the disease have permitted us to demonstrate that the neurons have a constellation of minor defects, but that no degeneration is occurring, and that our brain need MECP2 at all times. Whenever the gene gets inactivated the disease appears.

Genetically modified mice have made crucial contributions to our understanding of Rett syndrome. Image courtesy of Understanding Animal Research.

Genetically modified mice have made crucial contributions to our understanding of Rett syndrome. Image courtesy of Understanding Animal Research.

Rett syndrome is mainly a neuronal disease, and obviously the amount of research we can do with the girls’ brains is limited. Because of this a range of mouse models of the disease have been instrumental for the study of the pathology. Furthermore, the same mice have permitted scientists to find the first molecular pathways that appear altered in the disease leading to test some therapeutic molecules in mice. Translational research leads to a clinical trial; and this is the case here, for example a clinical trial of IGF1 therapy is currently under way. Importantly, in 2007, Professor Adrian Bird and colleagues at the University of Edinburgh demonstrated in a mouse model that it is in principle possible to reverse Rett syndrome, and that MECP2-related disorders can be treated even at late stages of disease progression. However, the functional role(s) of MECP2 and their relevance to different aspects of development and neurological function are not fully understood, and different mutations in the MECP2 have varying effects on these roles, which any treatments will have to account for. Research indicates that too much MECP2 expression can be damaging, so scientists will need to find a way to express just the right amount of MECP2, in just the areas it is required. The clinical community has decided that no drug can be given to Rett syndrome girls without having first been tested in two different laboratories and on at least two diverse mice models of the disease. Nevertheless, this research is very promising, and not just for those with Rett syndrome and their families, as the insights gained through developing therapies for Rett syndrome are likely to be applicable to therapeutic strategies for a wide range of neurodevelopmental disorders. Studies in mouse models of Rett syndrome have a crucial role to play in this ongoing work.

proRETT is an association founded in 2004 by parents of children born with Rett syndrome, who began their activity by raising funds for the US based Rett Syndrome Research Foundation (now the International Rett Syndrome Foundation). proRett now supports the work of top Rett researchers in Italy, the UK and USA. I am a professor of molecular biology who has worked on MECP2 since I was a post-doctoral fellow in the team of the late Dr Alan P Wolffe at the National Institute of Child Health and Human Development.

In 2005 I met with proRETT to launch a collaboration in order to accelerate the scientific interest in the disease in Italy and abroad, and over the next few years   we worked together to organize two international scientific meetings (e.g. the European Working Group on Rett Syndrome) and attracted the interest of several Italian researcher to the disease. In 2010 proRETT felt the necessity to support more research in Italy and decided to open a laboratory – the San Raffaele Rett Research Center  – at the prestigious San Raffaele Scientific Institute in Milan. The laboratory, which I lead, employs 2 post-doctoral scientists, 3 PhD students and an undergraduate student. Further a second laboratory employing 8 scientists, supervised by myself and Danish researcher Dr. Charlotte Kilstrup-Nielsen, and fully dedicated to Rett syndrome is located at the University of Insubria in Busto Arsizio. As I outlined earlier, our research, as well as that of many other laboratories in the world, is interested in defining the molecular pathways that get deregulated because of a dysfunctional MECP2.  We are also examining the role of the gene during early development and outside of the brain itself. Eventually we hope to develop some novel protocols of gene therapy that can reverse Rett syndrome.

The Rett syndrome research team at the University of Insubria in Busto Arsizio

The Rett syndrome research team at the University of Insubria in Busto Arsizio

Because one of the two labs supported by proRETT is in Busto Arsizio and in Busto Arsizio there is a strong female volleyball team – Unendo Yamamay – almost one year ago we decided to organize a match of the Yamamay team dedicated to proRETT. The idea was for a female team to support research on a disease that affects girls, with both volleyball and research in the same town. The team were keen to help and the event was scheduled to be held on Saturday 15th March 2014. That evening we would have been the guests of Yamamay, and we were going to hold a raffle to raise money for research.

Unfortunately, once the event was announced last month, the trouble started. It began when the Busto Arsizio branch of the large Italian animal rights group the Lega Anti Vivisesione published decontextualised images of dead mice (seems familiar – SR)not belonging to my lab on their facebook page and claimed that our activities were unscientific  in order to stir up anger amongst their supporters against our lab (you can read more details about this in Italian here). They then tried to start a boycott of Unendo Yamamay and started a mass  e-mailing campaign, writing on social networks and to the proRETT and Unendo Yamamay. At the end of this nightmare, and because the local police headquarters was not confident about keeping the event safe from disruption by violent animal rights extremists, we had to give up. The match went ahead but proRETT were no longer guests, with Unendo Yamamay issuing a statement expressing their extreme regret at the events leading to the cancellation that had “caused serious harm to persons engaged daily in medical research against this terrible disease”.

Organizers had hoped to sell 6 thousand tickets for the lottery in aid of Rett syndrome research

Organizers had hoped to sell 6 thousand tickets for the lottery in aid of Rett syndrome research

The cancellation was felt as a tragedy by the parents, who, obviously, felt themselves even more alone than before. Because of that we decided to hold the raffle in our university in Busto Arsizio on Friday evening the in order to raise some money for proRETT, where we were joined by some parents and girls with Rett syndrome, as well as several journalists, and the president of Pro-Test Italia, who chose to show solidarity by attending. In the end we raised almost 6,000 euros from the raffle, less than we had initially hoped, but enough to show us and the parents of girls with Rett syndrome that there are still good people who are prepared to stand up for vital research.

We need to make sure this never happens in Italy again. This fight goes beyond Rett girls but is in the name of the progress of biomedical science in Italy and in the world; it is in the name of a future with less suffering. We would like the parents of Rett girls  and researchers dedicated to curing this disease to not feel alone, so we ask you to join good people in Italy and across the world to show your support for our girls, and your contempt for animal rights extremism, by making a small donation to proRETT.

Thank you.

Nicoletta Landsberger

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

Comments are closed.