Treating Synaptic Dysfunction

RETT SYNDROME RESEARCH TRUST WEBSITE

Last month brought me to Houston, Texas to attend a fascinating meeting organized by Huda Zoghbi and Morgan Sheng and co-sponsored by RSRT. Entitled Disorders of Synaptic Dysfunction, the event was the inaugural symposium of the recently established Jan and Dan Duncan Neurological Research Institute, directed by Dr. Zoghbi.

The two-day meeting brought together a heterogeneous group of scientists from academia (senior and junior faculty as well as post-docs and graduate students), industry, NIH and other funding agencies.

The focus was not on  a single disease but rather on a group of disorders (Rett, Angelman, Fragile X, autism, Tuberous Sclerosis) that share a common cellular phenotype: abnormal synapse activity.

It’s no surprise that some of the talks that generated the most buzz came from labs that are doing very clinically relevant research. These include the labs of Mark Bear at MIT, working on Fragile X, and Ben Philpot at UNC whose lab works on Angelman Syndrome.

Like Rett Syndrome, Fragile X is a single gene disorder, caused by mutations in a gene called Fmr1. When Fmr1 is mutated, protein synthesis fails to shut down, leading to excess. Some years ago Dr. Bear proposed that compounds which can block a certain type of receptor, mGluR5 (which triggers the burst of synaptic protein synthesis) might counteract over-expression of protein and thereby cancel out the damaging effect of Fmr1 deficiency. His theory has proved correct, and clinical trials of mGluR5 antagonists are currently ongoing at multiple pharmaceutical companies.

I first met Dr. Bear almost a decade ago, when he was just beginning to formulate what is now commonly known as the mGluR5 theory of Fragile X.  His lab is currently funded by RSRT to explore protein synthesis in the Rett mouse models. Dr. Bear hypothesizes that Rett may be due to under-expression of proteins. If his hypothesis holds up, pharmacological manipulations of mGluR signaling will be pursued.

Ben Philpot’s talk also generated excitement. He discussed a high-throughput screen that has yielded a compound which can activate the silenced Angelman Syndrome gene, UBE3A. Dr. Philpot is currently funded by RSRT to pursue a similar approach for the silent MECP2 gene on the inactive X chromosome.

Mike Greenberg spoke about MECP2 and shared unpublished data that has come about from his collaboration with Adrian Bird via the RSRT funded MECP2 Consortium. (More on that in the months to come.)

Jackie Crawley of the NIH gave a brilliant talk on how “autistic mice” are being characterized to yield a plethora of new information.  For me the highlight of her talk was hearing recordings of mouse “speech”. She shared a variety recordings and I was taken aback by the complexity and richness of the sounds, which left me yearning for an analysis of Rett mouse vocalizations.

After a lively cocktail hour it was back to work with dinner plates in hand. Drs. Zoghbi and Sheng divided the attendees into three working groups: 1) dysfunction of proteins of the synapse 2) dysfunction of nuclear/cytoplasmic proteins 3) young investigators and junior faculty.  Masquerading as a 30-something I happily joined the third group.  I was struck by the fearlessness and boldness of these young scientists. There were not shy about criticizing the status quo and what could be done differently to enhance the research progress. I came away feeling buoyed and reassured that science is in good hands with this new generation.

The following several hours of discussion, led by Rodney Samaco and Mingshan Xue and facilitated by NIMH Director, Tom Insel, were intellectually stimulating and entertaining. Below is a visual output of our intense discussion.

A few personal reflections on the symposium

• Over and over again throughout the meeting I heard comments from autism researchers such as: “Where would we be without the syndromic autism animal models like Rett and Fragile X? We’ve learned so much from them”.  More than once I found myself thinking that as horrible as Rett is at least the genetics of the disorder are clear-cut – Rett’s silver lining.
• The meeting provided an opportunity to meet some scientists with whom I had communicated by email and/or phone, but never met in person. People like Pat Levitt, Freda Miller and Michael Palfreyman.  It was a reminder of how many people over the years have taken the time to discuss their work and possible synergies to Rett Syndrome.
• Drs. Zoghbi and Sheng kept everyone busy from the moment the meeting started to the moment we left, including an intense working dinner. I tend to do the same thing  at meetings that I organize, but always feel like I’m being a bit of a slave driver. Never again, however, will I feel guilty. If Dr. Zoghbi thinks it’s acceptable, then so do I!

Kudos to Drs. Zoghbi and Sheng for a stimulating meeting and thank you both for inviting me.

Science Translational Medicine, which co-organized the meeting, will be publishing a white paper on the proceedings.
RSRT will let you know when the paper is available.

The Person Behind the Scientist

Jonathan Kipnis and his lab members Noel Derecki and James Cronk authored the  recent Nature paper entitled Wild type microglia arrest pathology in a mouse model of Rett Syndrome. Watch the videos below for some insight into what makes them tick.

Jonathan Kipnis, Ph.D.

Noël Derecki, Ph.D.

James Cronk

Bone Marrow Transplants – Proceeding with Caution

RETT SYNDROME RESEARCH TRUST WEBSITE

The recent publication of the Kipnis paper in Nature has generated understandable excitement and questions in the Rett community. Email and Facebook are difficult vehicles for providing proper answers. Rett Syndrome is complex, and so is the research; this work doesn’t lend itself to sound bites. I know Rett mothers and fathers are often tired and overworked, but I encourage you to find fifteen minutes to sit down together with a cup of coffee, listen carefully to what these researchers are discussing in the video interview, and come away more deeply informed.

The paper has already been euphemistically coined the bone marrow transplant paper. I’ve occasionally called it that myself, sometimes in the presence of Dr. Kipnis, who promptly says, “Please don’t call it that. There is so much more information in that paper than just the bone marrow experiments.” He’s right. In fact, there is enough material to have generated multiple publications.

The paper is attracting an unusual amount of attention in the scientific community, and this is bound to stimulate more interest in Rett Syndrome and the role of the immune system in neurological disorders. The bone marrow transplant result is understandably what families gravitate to because of the potential for clinical application, but it’s important not to ignore the other findings, because they too could point to eventual treatments. In fact, it is my fervent hope that in time, new discoveries will make it possible to manipulate the immune system through a safer route.

Bone marrow transplants (BMT) have been used since 1968 to treat an increasingly wide range of disease, including cancers, metabolic diseases, inherited red cell disorders and immune disorders. The treatment can be lifesaving. It can also be fatal. Accompanied by chemotherapy and/or radiation treatment, BMT is a serious and grueling procedure with significant side effects. The combined expertise of specialists in pediatric BMT, as well as in Rett Syndrome,  together with basic scientists is crucial to minimizing risk as much as possible.

As part of a fact-gathering process, RSRT has been facilitating talks between top pediatric transplant centers and Sasha Djukic, Director of the Rett Syndrome Center at the Children’s Hospital at Montefiore, Jonathan Kipnis and his lab members and, most recently, NIH. Discussion includes defining the data needed to consider clinical trials. This must be completed and thoroughly evaluated in order to design the best possible treatment protocol. Independent confirmation of the results achieved by Dr. Kipnis and his team is a standard requirement; this work is already underway. Further experiments in the Kipnis lab itself are ongoing, and we can expect more new information to emerge.

It is perhaps timely for me to reiterate that RSRT is very aggressive about research, and conservative about clinical application. I want to be crystal clear on one thing – parents should not take it upon themselves to pursue BMT for their child. As the mother of a severely afflicted daughter, I understand all too well the desperation for treatment. As Executive Director of RSRT, I understand equally well the importance of applying meticulous due diligence. RSRT does this in all the work we undertake, the projects we review, our financial decisions, and certainly in our approach to clinical trials.

I share your excitement, your urgency and your trepidation, and RSRT will continue to inform you of new developments as they unfold.

- Monica Coenraads
Executive Director, RSRT

Bone Marrow Transplant Stops the Development of Symptoms in Model of Rett Syndrome

RETT SYNDROME RESEARCH TRUST WEBSITE

Click Here to Read Press Release

A paper published online today in the high-profile journal, Nature, describes the results of using a bone marrow transplant to dramatically stop the development of symptoms in pre-symptomatic male and female mouse models of Rett Syndrome.  The work was undertaken in the neuroimmunology laboratory of Jonathan Kipnis, Ph.D. and his team at the University of Virginia.

That a bone marrow transplant could arrest such a severe neurological syndrome such as Rett is quite unexpected and provides us with yet another strong example of how tractable this disorder appears to be – at least in the animal models.   Experiments are now underway in the Kipnis lab to test whether reversal of advanced symptoms via bone marrow transplants and other modulation of the immune system is also possible.

This work was funded by the Rett Syndrome Research Trust and the Rett Syndrome Research Trust UK.

Jonathan Kipnis and Noël Derecki

Jim Cronk and Noël Derecki

The clinical relevancy of this work makes this paper of obvious and significant interest. But the authors don’t stop there. The paper describes data that could help us better understand how MeCP2 deficiency leads to symptoms.  They introduce the concept of a powerful connection between the immune system and Rett Syndrome and open the door not only to bone marrow transplants as a treatment modality but potentially to other immune therapies as well.

To help you understand the key findings and implications we invite you to watch the videos below. Please watch the animation of the experiments first followed by the interview.

We would like to take this opportunity to thank Jeff Canavan of NewsAnimation for volunteering his time and effort to create the beautiful animation below. Jeff has a daughter with Rett Syndrome and founded, with his wife Sarah, the Kate Foundation for Rett Syndrome Research.

ANIMATION OF EXPERIMENT

We thank Jeff Bemiss for donating his filmmaking expertise, substantial time, energy, equipment and editing resources to film the interview below. He comes to our cause through his friendship with the Canavan family.

INTERVIEW WITH RESEARCHERS

BioWorld Insight feature article on Rett Syndrome

A recent issue of BioWorld Insight, the weekly newsletter that provides behind-the-scenes analysis and commentary on the biotechnology industry, included a feature article on Rett Syndrome.  The piece explored how recent interest in rare diseases on the part of pharmaceutical/biotech industry may impact research in disorders such as Rett Syndrome and Fragile X.

Science, Rare Disease Push Help Developmental Disorders

By Anette Breindl
Science Editor

In its last issue of the year, Science – one of the premier  journals for peer-reviewed scientific research – published both what it considers to be the biggest breakthrough of the past year, and areas to watch for the next year. For 2012, one of those hopeful areas was “treating intellectual disability.”

According to the story, “the cognitive deficits and behavioral problems caused by Rett, Fragile X and Down syndromes have long been considered irreversible. In each syndrome, a genetic glitch causes brain development to go awry even before birth. But recent work with mouse models of those conditions suggests, remarkably, that some cognitive and behavioral symptoms may be reversible.”

For Rett syndrome, Monica Coenraads traces the realization that developmental disorders do not necessarily mean a lifetime of disability, to a paper published almost exactly five years ago, in the Feb. 8, 2007, issue of Science. In that paper, researchers reported that when they replaced the mutated MeCP2 protein with a normal one in adult mice with full-blown Rett syndrome – animals whose life expectancy without medical intervention could be measured in days – the mice could be rescued, and many of their symptoms reversed.

[READ MORE]
Posted with the permission of AHC Media, publishers of BioWorld Insight, http://www.bioworld.com

Prof. Adrian Bird Gives Speech at London Event

Professor Adrian Bird needs no introduction to anyone who follows Rett Syndrome research. His list of accomplishments includes discovering the MeCP2 protein, developing multiple animal models for the disease and authoring the seminal 2007 Science paper which introduced the startling concept that Rett Syndrome and other MECP2-related disorders are curable.

He was the Guest of Honor at the Reverse Rett London event hosted by RSRT UK which took place on December 1, 2011. Below is a video of his remarks on the vitality of Rett research, the importance of maintaining global efforts in the field, and the possibilities that lie ahead.

Family’s Passion Spurs Research Success for Cystic Fibrosis

RETT SYNDROME RESEARCH TRUST WEBSITE

02/10/2012 – Forbes.com

Turning loss into hope, family offers inspiration — and a few lessons about drug discovery

A poignant story in Thursday’s Boston Globe describes how the O’Donnell family of Boston channeled their love of a son, Joey, who died tragically at the age of 12 from cystic fibrosis, into a successful mission to develop impactful new treatments for this terrible affliction.

The narrative – expertly told by Brian McGrory (see here for my favorite example of his wonderful writing) – is a testament to devotion, persistence, the power of parental love, and the resiliency of the human spirit.  It is essential reading for these qualities alone.

[READ MORE]

What Success Looks Like

Rett Syndrome Research Trust Website

Doris Tulcin – A Mother’s Love Raises the Bar For All Non-Profits

Half a century ago, a mother whose baby daughter was diagnosed with a life-threatening genetic disorder decided to fight it. Doris Tulcin is that mother, and Cystic Fibrosis is the disease against which she went to war. First identified in 1938, Cystic Fibrosis affects roughly 30,000 children and adults in the United States and is therefore, like Rett, classified as a rare disease. In 2010 the Cystic Fibrosis Foundation generated donations in excess of $300 million, $120 million of which was raised from the general public. Now, Vertex Pharmaceutical’s VX-770, the first drug that treats not just symptoms but the underlying genetic cause of Cystic Fibrosis, has been fast-tracked through FDA approval.

Doris Tulcin has been a valued advisor to RSRT since our inception three years ago. The following in an excerpt from a recent conversation between Mrs. Tulcin and RSRT Executive Director, Monica Coenraads.

MC:  Congratulations! You must be thrilled with the early FDA approval—it’s been a long road and I know CF families are rejoicing today!

DT:  It’s mind-blowing!  VX-770 is for a small group of patients that have a rare mutation but will literally change the disease and these kids completely.  And that’s what we are working on now for 90% of the patients with the major mutation.  Things are moving really well.

MC:  CFF provided substantial scientific, financial and clinical support for the development of VX-770, including the investment of $75 million.  When I think about the vast amount of money CFF raises, with a patient population similar to Rett, I can’t help but ask myself, How have you done it?  Are there specific decisions that you think have been pivotal?

DT:  Well, you must remember that we have a long history; we’ve been in business since 1955.  So it took over fifty years to get to where we are today.  Going back in time, it is so hard to pinpoint any one thing.  But we really focused on research, as you are doing.

MC:  Of course, the scientific tools and knowledge that were available fifty years ago are so very different from research today.  Everything has accelerated.  Yet I know that getting to this point with Cystic Fibrosis has been a process with many components.

DT:  From 1980 on is where we really took off with developing research programs with major universities, and by the 1990’s we became increasingly business-oriented and
focused on working with the biomedical community and pharmaceutical companies for drug development.

MC:  As with Rett syndrome, the Cystic Fibrosis population is small.  You know RSRT has a PSA that’s running in Times Square, the same screen that was used for the CFF.  So 1.5 million people will see it every day for three months.  How important do you feel it is to raise general public awareness, in terms of the ability to raise research funds?

DT:  Name recognition is very important.  The general public doesn’t have to understand the disease but they certainly have to recognize the name.  You know, people will say “I’ve heard of Cystic Fibrosis”— well, what do you think it is?  They can’t describe it.  They haven’t the vaguest idea, but they’ve heard of it.

MC:  And you think that correlates to the amount of money you raise?

DT:  I do. Our chapters raise roughly $100 million a year. But keep in mind that it took decades to get where we are today.

MC:  For RSRT, at the three-year mark, most of our revenue comes directly from affected families and their networks.  Do you think the same applies to you, or do you have people just spontaneously donating to CFF without any personal connection?

DT:  I think now we do, yes. But what we started with and built on was indeed that personal commitment and involvement to develop networks of family and friends.  The activism of those who are personally affected is crucial.

MC:  How would you compare the current philanthropic landscape to what you’ve seen in past decades?  These are difficult economic times for many.

DT:  Yes, we are still in a bad economy now and that reflects on contributions, there’s no doubt. It’s tough, and there’s always competition and distraction.

MC:  On a personal note, how is your daughter doing?

DT: Oh, thank God, she’s doing well.  She’s a grandmother!  My grandchildren have introduced me to Facebook, so we communicate in that way, because they’re all grown up and don’t have time for other things. But we do that too with the foundation, we’re on everything you can think of— Facebook, Twitter, YouTube.  Everything now is sent electronically.  The website is being updated all the time, you can get every bit of information at any time off that website.

MC:  Yes, the fact that electronic media is now ubiquitous worldwide has really changed the flow of information in important ways for families dealing with something like a rare disease. The ability to be in instant communication with others who really understand relieves some of the isolating strain of constant and intense caregiving, as well as keeping people informed of current developments. That families can so easily connect and learn from each other is vital and sustaining.  The day-to-day struggles can be so overwhelming sometimes for Rett parents that there’s not always a lot of energy left for what I feel is truly going to change our children’s lives—the research.  What are your thoughts?

DT:  There is no doubt that you really have to find ways to stay focused, and I think that was one of our biggest successes.  Care has been important but it is research that’s absolutely critical; it’s the only way to move forward.

MC:  Research has always been my commitment, and I hope the work of RSRT will prosper as brilliantly as that of the CFF. Congratulations again on VX-770 and
thank you for your guidance and inspiration.

DT:  Monica, I know how tremendously devoted you are to this fight. The Rett community is very blessed to have you.

MC:  Thank you, Doris.

Letter from the Executive Director

RETT SYNDROME RESEARCH TRUST WEBSITE

Dear Friends,

This October will mark fourteen years since my daughter, Chelsea, was officially diagnosed with Rett Syndrome. On that day I made my then two-year-old daughter a promise: I would do everything in my power to free her from Rett Syndrome.

In pursuit of that promise I co-founded two organizations: first the Rett Syndrome Research Foundation in 1999 (later merged with IRSA to become IRSF) and more recently the Rett Syndrome Research Trust. Through my work I have supervised peer-review for almost a thousand research applications, organized numerous scientific symposiums and think tanks, heard countless science talks and spoken to more scientists than I ever imagined possible.

My work with RSRT is ambitious and often difficult, especially when also dealing with the never-ending challenges of raising a child with complex medical needs. However, working with like-minded trustees, organizers of events both big and small, and the founders of organizations who support our efforts has been a supremely rewarding experience. Their drive to maximize research funds in a no-nonsense, get-the-job-done fashion has been inspiring and energizing.

As I stand on the threshold of the New Year I feel, for the first time in fourteen years, that 2012 may see the efforts of the scientists and the donors who support them begin to bear fruit – a year that could prove to be paradigm-shifting in how we think about fighting Rett Syndrome. A year where we may begin to test, via clinical trials, whether what works in the animal models will actually work in children.

Much work remains to be done, both scientifically and financially. The research that lies ahead needs to be exponentially expanded. Clinical trials will be particularly expensive. We need your help. If you’ve been hesitant about fundraising please consider this your own personal invitation.

In joining our efforts you will become part of an extraordinary group of national and international volunteers – discerning, bold, tenacious and unabashedly intense. Because of their vision and commitment RSRT had a remarkable year. Our young organization, with the tireless work of motivated volunteers and contributors and no staff, beyond myself, moved Rett research forward in 2011:

• RSRT committed $3.6 million to new research in 2011. This is a record amount for any Rett advocacy group in a given year.
• A $1 million gift created the MECP2 Consortium.
• Despite difficult economic times, we saw a 60% increase in donations.
• RSRT launched a 3-month awareness campaign in Times Square seen by millions throughout the holiday season, including New Year’s Eve.
• In 2010 96% of our donations funded our research program – a statistic we expect will hold up in 2011 (our financial statements will be available soon)

As I bend down to lay my 15-year-old daughter gently into her bed each night we often stare intently into each other’s eyes. As her gaze bores into me I feel her holding me to my promise. I invariably ask myself “Did I do right by her today?” It is with serious and deep purpose that I renew my obligation to her and to each person with Rett Syndrome. This sense of responsibility extends also to our supporters and volunteers who donate money, time, and energy. Their confidence in our work reinforces our collective strength and will to defeat Rett Syndrome.

If you know a child or adult with Rett Syndrome please consider making 2012 the year you become more involved with our efforts.

If you are the parent of a child with Rett, perhaps you’ve made a similar promise to your daughter. Help us to fulfill your promise … and mine.

Monica Coenraads
RSRT Executive Director

RSRT Trustees:
Adrian Bird, PhD, Monica Coenraads, Heidi Epstein, Ingrid Harding, Lawrence Mattis, Tony Schoener

:::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::

I’d like to support your efforts by making a donation. (Recurring monthly donations also possible.)

I’d like to become involved with an existing annual event.

I’d like to discuss starting my own event.

I would like to learn more about RSRT and how I might contribute.

The X Factor

 RETT SYNDROME RESEARCH TRUST WEBSITE

Those of you who follow the efforts of RSRT know that one of the treatment strategies we are pursuing is the reactivation of the MECP2 gene on the inactive X chromosome.

A quick refresher for those in need of one: mutations in MECP2 cause Rett Syndrome (and a host of other disorders as well). MECP2 is on the X chromosome. Males have one X (and one Y) and females have two X’s, but in order to prevent duplication of genetic material randomly inactivate one of the X’s in every cell. This means that in females with Rett about 50% of cells have the normal MECP2 gene expressed and 50% have the mutated gene expressed. In theory, if we can find a way to reactivate the normal MECP2 gene on the inactive X chromosome, we may cure the disease.

RSRT funded investigators currently pursuing this line of inquiry include Antonio Bedalov of the Fred Hutchinson Cancer Research Center in Seattle, Marisa Bartolomei of UPenn and Ben Philpot and Bryan Roth of UNC.

The reactivation effort now has a new player – Jeannie Lee, M.D., Ph.D. of Harvard University. She is a leader in the X chromosome field and we welcome the significant intellectual and technological resources that she will bring to this endeavor.

MC: Congratulations Dr. Lee on receiving RSRT funding. Tell us a bit about yourself and how you came to be interested in Rett Syndrome.

JL: Growing up I dreamed of being a physician. While I was in college I got involved in undergraduate research and I realized that I really enjoyed doing research. During my senior year I couldn’t decide whether to become a physician or pursue my new-found interest – science, so I decided to keep my options open and enrolled in an MD/PhD program at Penn. By my third year I realized I wasn’t going to practice medicine and would instead hope to make contributions to medicine via science. My interest in X chromosome inactivation (XCI) began as a graduate student in the lab of Robert Nussbaum.

MC: Dr. Nussbaum was actually one of the first scientists that I connected with in 1998 when my daughter was newly diagnosed. He was very kind and offered lots of practical and helpful advice as I started the Rett Syndrome Research Foundation (which later merged with IRSA to become IRSF).

JL: He was a great mentor. In his lab I worked on Fragile X. While attending various genetics meetings I heard some interesting talks on XCI that really caught my attention. I chose to do my post-doc in Rudolf Jaenisch’s lab at MIT and that is when I began working on XCI. Although the Jaenisch lab was not an XCI lab, all the necessary tools were there. Jaenisch was very well versed in knockout technology and transgenics and the lab was full of very bright people. So for me, it was the perfect place to be.

I set up my own lab at Harvard in 1997 and have been working on XCI ever since. To better understand the mechanics of XCI, I incorporated more molecular biochemistry-driven approaches to the mouse system. During the past few years I’ve been thinking more and more about how to apply the lab’s experience, tools and resources to a clinical problem and Rett is the perfect choice.

MC: Why Rett and why now?

JL: Combination of two things. One, the realization that Rett is curable. There is the beautiful mouse model work of Adrian Bird that shows us that you can be born with this deficiency and be cured through gene therapy or reactivation of the normal copy of MECP2. That is profound. How many congenital diseases can we say that about? Rett is one of those congenital genetic diseases for which a cure could actually happen.

And two, the tools are in place to do the necessary experiments. I feel the time is right to take the platform technologies we’ve developed and use them to identify potential therapeutics for diseases. Rett is definitely one of the targets. I’ve been interested all along in applying knowledge of basic principles to cure disease but needed to develop the tools first. We’d rather start simple and Rett gives us this chance.

MC: I don’t think I’ve ever heard Rett referred to as “simple” but I’m sure glad you think so.

JL: Simple from a mechanistic standpoint because Adrian has already shown us that it can be reversed, and that, together with the fact that Rett is a single gene disorder, which is a huge advantage, gives us hope that we’ll succeed, that we won’t be working in vain. There is actually a huge amount of interest in Rett from the scientific community.

MC: Let’s talk about the experiments you are proposing. Your plan is to develop an assay using mouse cells that will glow when the inactive MECP2 gene is activated. You’ll be using the screening facilities of the Broad Institute in Cambridge, MA, which are quite impressive.

The Broad is really a unique facility – an experiment of sorts about a new way to tackle science. It brings together an eclectic group of scientists from its partner institutions that include MIT, Harvard and the affiliated major teaching hospitals (Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Children’s Hospital, Dana-Farber Cancer Institute, and Massachusetts General Hospital). The combination of some of the best minds, unprecedented technological resources and some pretty deep pockets makes for a fertile working environment.

JL: Yes, that’s right. We are quite excited about the project and our ability to leverage the resources of the Broad. We will work with Stuart Schreiber and Nicky Tolliday and others who run the high-throughput screening group within the Broad Institute Chemical Biology platform. They have the know-how and the necessary robotic devices. We simply would not be able to conduct this screen without the Broad.

MC: Just this week an interesting paper was published in Nature describing a class of cancer drugs called topoisomerase inhibitors that have the ability to activate the silent UBE3A gene in Angelman Syndrome. The work was spearheaded by Ben Philpot and Bryan Roth who now have RSRT funding to pursue a similar approach for MECP2. This work provides strong proof-of-concept that these screens can work.

JL: The paper is exciting and promising. I do believe our screen is going to work.

MC: Dr. Lee, we wish you the best of luck as you begin this project and look forward to hearing about your progress. Happy holidays to you, your family and your lab.

Below is a short video of Nicky Tolliday explaining the Broad’s high-throughput screening capacity.