As promised, I am going to attempt to explain some of the Rett syndrome research, for those of you who don't already have your PhD and/or haven't been to a lot of conferences on Rett syndrome. This is a daunting task. It's tricky to understand and tricky to explain. The amount of research out there right now is overwhelming, but that is the good news! There are many reasons to be hopeful.
This post is just a snapshot of what I find interesting, with links to more helpful writers. I will definitely be missing some important findings. Please let me know of any errors and I will update as needed.
Rett syndrome was first described by Dr. Andreas Rett in the 1966. His original German publication was translated into English in 1977.
Rett syndrome became more well known in the English-speaking world when Dr. Bengt Hagberg published an article in the Annals of Neurology.
In 1999, the year Abby was born, the MECP2 gene was linked to Rett syndrome at Baylor College of Medicine by Ruthie Amir and her group, led by Dr. Huda Zoghbi. Abby's mutation is on the MECP2 gene, as it is with most people with Rett syndrome. Recently, other genes have been linked to Rett syndrome, namely CDKL5 and FOXG1. Rett syndrome is an X-linked dominant disorder and it is therefore usually only found in girls.
In 2007, a study by Dr. Adrian Bird showed the reversal of many Rett symptoms in a mouse model. This groundbreaking discovery demonstrated that brain abnormalities in Rett syndrome are not permanent. This raised interest in Rett research around the world. Toronto scientist Dr. James Eubanks has been able to replicate this finding in the female mouse model. He has even seen dramatic improvement very late in development in the mouse model. Although this method cannot be directly used in humans, these studies demonstrate that treatments for Rett syndrome are quite feasible, even for older individuals.
Recent advances in stem cell technology have made it possible to produce a human Rett nerve cell in the laboratory. This new type of technology does not involve the use of embryonic cells, so it holds more promise for wide use in research. Dr. James Ellis is a leading Canadian researcher who works with these reprogrammed cells. In 2010, Dr. Alysson Muotri's group got world-wide attention for developing a stem cell system derived from people with Rett syndrome to test drug treatments. The timing for this coincided with one of the first major clinical trials for Rett syndrome in Boston.
There are other recent, noteworthy studies, for those who want to learn more:
- microglial cells and their role in Rett syndrome
- conditional knockouts - mice engineered to study specific groups of neurons, such as GABA-releasing neurons in MECP2-null mice (some very cool videos at this link)
- L1 sequences of DNA, commonly known as jumping genes
- read-through technologies for nonsense mutations, including a study by Andreea Popescu from Dr. Eubanks' lab (She studied Abby's mutation, 294X, among others.)
There is every reason to be excited about Rett syndrome research! From what I've heard, there's an abundance of ideas about what to do next. We just have to keep raising awareness and funding to keep the ball rolling.
Speaking of awareness and funding, keep your eyes open for news of the new Ontario Brain Institute. The process is moving at government speed, but it will hopefully be a worthwhile endeavour. You might also like to follow the advocacy efforts of Neurological Health Charities Canada and, as always, the Ontario Rett Syndrome Association.