Annual Report 2011-2012 by Rachael Stevenson

annual report 2011-2012

Annual Report 2011-2012

contents

Rett Syndrome Research Trust UK

introduction

6-9

Introduction

Where your money goes

Learning that your child has Rett Syndrome is devastating. Learning that scientists believe Rett Syndrome could be the world’s first curable brain disorder brings hope. It also brings a determination to do everything in our power to speed the day when the research moves out of the lab and into our children’s lives.

4-5 What we did

8 research projects funded

£424,477 delivered to research

122% increase on research funding

When we founded Rett Syndrome Research Trust UK in 2010, we were a group of parents committed to funding research that would make Rett Syndrome a thing of the past. Inspired by the success of the Rett reversal experiments, we were determined to help drive the science to its ultimate conclusion: an effective treatment, even a cure, in our daughters’ lifetimes. Since then, progress has been rapid. We are confident that the next few years will bring clinical trials and pilot studies of existing medication and procedures, to explore whether applied individually or even in combination, they can relieve symptoms. Our little charity has grown quickly. In the last year, we more than doubled the amount contributed to research, thanks to the tireless efforts of our extraordinary community of fundraisers. We aim to double this again in the next two years, to support existing research projects and enable new ones. A heartfelt thanks to everyone who has donated money or time, run races, climbed mountains, completed endurance tests, baked cakes, sold raffle tickets and put their heart and soul into changing the future for our children: you are the lifeblood of Rett Syndrome Research Trust UK.

Rachael Bloom Executive Director

fighting to reverse rett

Annual Report 2011-2012

Rett Syndrome Research Trust UK

Developed new projects to ensure sustainability

The charity’s brand, literature and website were redeveloped to gain maximum visibility and consistency across the UK. Development of our Fundraising Strategy has yielded exponential growth in community fundraising: Participation in team challenges and events alone quadrupled from 2011-2012

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Increase in Just Giving fundraising pages from 85 to 212 from 2011 to 2012.

Rett Syndrome Research Trust UK

what we did

Work with Trusts and Foundations have yielded over £16,000 in project grants from The Big Lottery Fund, The Rayne Foundation, The Margaret Murdoch Charitable Trust, The Liz and Terry Bramhall Foundation and others.

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What we did

Kept our costs low

Exceeded fundraising goals

Day to day running costs

Reinvestment in the charity

Increased income on London event by 95%

5.5%

2.7% to

from

More than doubled Big Give income from

Earned recognition Won Best New Charity at the Charity Times Awards, Oct 2011

Won Best New Charity at the Just Giving Awards, March 2012

from

Named Charity of the Year 2012, by data insight company, Beyond Analysis

£53,213 £25,252

Research

91.8%

More than doubled our research committment from

from

£202,655 £103,806

fighting to reverse rett

£424,447 £191,464 5

Annual Report 2011-2012

Rett Syndrome Research Trust UK

What we did

Rett Syndrome Research Trust UK

Rett Syndrome = Life Sentence. Research = Freedom.

Finding compounds to reactivate the healthy MECP2 gene

Developing immune system therapies

Mutations in a gene called MECP2 are the cause of Rett Syndrome. Restoration of adequate levels of MeCP2 has been shown to undo the damage caused by a mutated copy of the gene, demonstrating the powerful reach of MECP2‘s influence as symptom after symptom disappeared in fully mature mouse models of Rett Syndrome. This astonishing breakthrough presents us with the urgent challenge of determining whether such results can be achieved in humans.

Ben Philpot, Ph.D., Bryan Roth, Ph.D., Mark Zylka, Ph.D. University of North Carolina at Chapel Hill

Jonathan Kipnis, Ph.D. University of Virginia

There are two primary approaches to developing treatments for Rett Syndrome. The first is to understand the function of the MeCP2 protein, and to design rational drugs to compensate for that deficit. And the second is to identify the various outcomes of having a deficiency in MECP2 and screen for anything that contravenes that outcome. Rett Syndrome Research Trust UK is supporting several projects pursuing both those approaches.

Jonathan Kipnis and his colleagues are examining the role of the immune system in Rett syndrome. They have already performed bone marrow transplants on mouse models, which resulted in Rett symptoms being reduced and relieved. This work could provide a foundation for potential immune-system therapies.

All girls with Rett Syndrome have a healthy MECP2 gene on their inactive X chromosome. Ben Philpot and his colleagues are working on a project to identify compounds that can reactivate this silenced but healthy gene – just as they did successfully with the gene for Angelman syndrome, UBE3A.

“If a drug could be identified to efficiently and effectively activate MECP2, we would be attacking Rett at its very root, with the potential of reversing the disorder. Our entire team is excited about the possibilities and we’re ramping up the project as fast as possible.” Ben Philpott Ph.D.

MECP2 Duplication Fund

0.3% MECP2 consortium

4.6%

Unallocated at year end

6.1%

Gene modifiers

14.8%

Increasing MECP2 levels

40%

Alleviating symptoms

33.4% 6

fighting to reverse rett

Annual Report 2011-2012

Rett Syndrome Research Trust UK

What we did

Identifying target genes and genes that modify MECP2 mutations

Rett Syndrome Research Trust UK

“This is a new and exciting experience for all of us. Our laboratories, like many in academia, have mostly worked solo. Now we are ‘opening our books’ to the Consortium, sharing information about Rett Syndrome research and collectively generating new ideas. By putting our heads together we want to accelerate research on a key question that has proven difficult to answer up to now: what exactly does MeCP2 do for the brain? The answer will have profound implications for attempts to treat disorders caused by mutations in the MECP2 gene. Now feels like the right time to push forward on this – the Consortium gives us a golden opportunity to make real progress.”

Monica Justice, Ph.D. Baylor College of Medicine Another potential avenue is developing interventions aimed at genes controlled by MECP2. Work is ongoing to identify which genes these are. Researchers are also considering the role of MECP2 modifier genes – genes that influence the severity of MECP2 mutation in an individual person. Some individuals are protected from MECP2 mutation due to mutations in other genes. Identifying these other genes could open up new routes to treatment.

Professors Bird, Greenberg and Mandel

MECP2 Consortium The MECP2 Consortium is a dynamic collaboration between the laboratories of three distinguished scientists, Adrian Bird, Michael Greenberg and Gail Mandel. The Consortium was recently formed to definitively determine how this complex protein, MeCP2, functions and how it exerts its powerful influence on the human brain.

fighting to reverse rett

Annual Report 2011-2012

Rett Syndrome Research Trust UK

thank you

you can help Give money

Give time

Making a monthly donation is the best way to help us give our children with Rett Syndrome and related MECP2 disorders a better future. It gives us a steady income stream so we can continue to invest in our research portfolio whilst supporting our commitment to ongoing projects. Sign up for a monthly direct debit here:

We are a community of changemakers who give our time to help reverse Rett in countless different ways. Offer your time by taking a challenge, hosting fundraisers or sharing your skill, talent or experience, whatever that is, to help us reverse Rett

The Trustees of Rett Syndrome Research Trust UK and Founders would like to acknowledge the volunteers, donors, supporters and fundraisers, whose determination and commitment makes our work possible; and our children, who are at the heart of everything we do.

www.reverserett.org.uk/donate

Board of Trustees

Give voice

Rachael Bloom Monica Coenraads facebook.com/ReverseRett

twitter.com/ReverseRett

Kelly Phillips Helen Simmonds

Andy Stevenson

#revRett

Call us 0161 955 4261 Professional Advisory Board Thomas Carroll David Greatrex Esther Marlow

Scientific Advisory Board Adrian P. Bird, Ph.D. Professor of Genetics, University of Edinburgh J. Michael Bishop, Ph.D. Arthur and Toni Rembe Rock Distinguished Professor, UCSF

fighting to reverse rett

David Moore James Seavers John Sharpe

Marc Souter David Thompson

Nathaniel Heintz, Ph.D. Professor; Laboratory of Molecular Biology, Rockefeller University

Luis F. Parada, Ph.D. Professor and Chairman, Department of Developmental Biology

Investigator, Howard Hughes Medical Institute

University of Texas Southwestern Medical Center at Dallas

Nobel Laureate

David M. Katz, Ph.D. Professor of Neurosciences, Case Western Reserve University

Geoff Duyk, M.D., Ph.D. Managing Director, TPG Growth

Christopher Lipinski, Ph.D. Melior Discovery, Inc.

Fred H. Gage, Ph.D. Laboratory of Genetics, Salk Institute of Biological Studies

Gail Mandel, Ph.D. Senior Scientist, Vollum Institute Investigator, Howard Hughes Medical Institute

Michael E. Greenberg, Ph.D. Chair, Department of Neurobiology, Harvard Medical School

Steven L. McKnight, Ph.D. Professor and Chairman, Department of Biochemistry

Franz F. Hefti, Ph.D. VP and Chief Development Officer, Chlorion Pharma

University of Texas Southwestern Medical Center at Dallas

Huda Y. Zoghbi, M.D. Professor, Departments of Molecular and Human Genetics Pediatrics, Neurology, & Neuroscience at Baylor College of Medicine Director, Jan & Dan Duncan Neurological Research Institute Investigator, Howard Hughes Medical Institute

“To all the scientists around the globe working towards a cure for Rett

Syndrome, we wish you determination, brilliance and godspeed.”

Rett Syndrome Research Trust UK Adamson House, Towers Business Park Wilmslow Road, Didsbury Manchester, M20 2YY Telephone: 0161 955 4261 Email: enquiries@reverserett.org.uk

reverserett.org.uk