We are in the early stages of planning our third research symposium devoted to rasmussen’s encephalitis.  The conference will take place next February on the campus of UCLA, one of our key researcher partners.  We have invited several notable individuals whose expertise crosses several research disciplines including rare disease genetics, infectious disease, epilepsy, immunology and clinical treatment.  We have received a strong response ensuring that both the heavy hitters and innovative thinkers will be attending and participating at the conference.

We held our first research conference in Deer Valley, Utah in October, 2010  which was followed up by our second symposium in New York City, February 2011.  Since that time we formally developed our research strategy which focuses on funding high impact projects designed to rapidly advance our understanding of rasmussen’s.  We are pursuing several avenues of research as the debate rages on whether RE is triggered by an auto-immune process or a viral/bacteria agent.  Most notably, we launched our virtual tissue bank which stores biological tissue resected during hemispherecotmy surgery at regional hubs rather than a centralized location.  In the last eight months we have shipped tissue from all over the world to our research partners in the US.

We are looking forward to the conference as the pace of activity in RE has increased in the last few years.  Johns Hopkins, Cleveland Clinic, Yale, University of Pennsylvania, Stanford and several foreign based research and treatment hospitals located in Australia, Britain, Germany, and Canada will all be represented.

Sponsoring a conference of this magnitude requires resources and while we are thankful for your past support, we do ask that you please continue to donate. Due to your generosity we remain committed to the cause and continue to make a difference.  Thank you.

Deer Valley October 2010

New York City February 2011

This week UCLA informed me that an article based on their initial findings from a research project funded and facilitated by the RE Children’s Project was being published.  To see the abstract of the article click here.  This is great news and a small first step as our research plans are implemented.

Essential to our research is the shipment of RE tissue immediately after hemispherectomy surgery to our research partners at Johns Hopkins and UCLA.  This past week we transferred tissue to UCLA and we were notified of another upcoming surgery in early June.  Our research plans call for a virtual tissue bank in which a two-way agreement exists to not only receive tissue, but to also make it available for investigators interested in rasmussen’s.  Rather than store the tissue at a central facility, we are pursuing a more nimble, flexible, and less costly approach that utilizes regional hubs to store the tissue for research purposes.

If you know of an upcoming hemispherectomy please contact me so that we can arrange for this precious tissue to be utilized in research to help other families avoid the nightmare of rasmussen’s.  Without the tissue we cannot advance our understanding of RE.  The RE Children’s Project pays for all of the transportation costs of the tissue and will arrange all logistical matters with the surgical hospital.  If you reading this blog and unfortunately have to consider a hemipsherecotmy or know of a friend in this situation please help us advance our research agenda.

The collaborative efforts to share brain tissue amongst our research partners is quite gratifying to see.  We have transferred tissue from all over the globe and from several prominent surgical hospitals.  We are indeed blessed to have been able to implement such a program.  This is no easy task.  A recent example of what can go terrible wrong is the debacle around the much publicized death of Junior Seau and the ugly “competition” that ensued to obtain his brain for research purposes.  This story is quite alarming, but shows how despite the best of intentions, ego, hubris, and money can influence medical research.

A few months ago we hired Thabiso Chirwa as our Research Coordinator to build and expand upon the foundation put in place by our first research coordinator, Joe Voros.  Joe did a great job and has moved on to a terrific opportunity, but we are very fortunate to have Thabiso on board and he has already had a huge impact.  Feel free to contact him directly at the e-mail below.

Thabiso Chirwa--RE Research Coordinator; tchirwa@mednet.ucla.edu

We continue to receive e-mails and calls from around the world from families impacted by rasmussen’s.  Here is one that arrived from Greece:

HELLO, I AM FROM GREECE.

I ‘VE READ YOUR EXCEPTIONAL BLOG WHEN I TRIED TO FIND SOME USEFUL INFORMATION FOR RE. I HAVE A 22 YEAR OLD SISTER WHO SUFFERS FROM THIS DISEASE ABOUT 11 YEARS. WHEN WE SAW YOUR BEAUTIFUL GRACE,WE THOUGHT THAT SHE LOOKS LIKE HER.  THIS RARE DISEASE WAS ABSOLUTELY UNKNOWN IN OUR COUNTRY, AS A RESULT MY SISTER HAD MANY SEIZURES FOR MANY YEARS AND NONE COULD SAY FROM WHAT SHE SUFFERS…ALL THESE UNTIL WE HAD OUR FIRST BIOPSY IN LONDON IN 2008. THAT MEANS ABOUT 6 YEARS WITH SEIZURES, MANY ANTI-EPILEPTIC DRUGS AND NO DIAGNOSIS.

YESTERDAY WE HAD AN APPOINTMENT WITH OUR DOCTOR, HEMISPHERECTOMY DOESN’T SEEM TO BE A “SOLUTION” FOR US BECAUSE AS I’VE ALREADY SAID MY SISTER IS 22.  NOW,THE PROBLEM IS IN THE LEFT HEMISPHERE AND IF THE WHOLE HEMISPHERE BEEN REMOVED SHE WILL LOSE THE SPEECH (WHICH HAS ALREADY AFFECTED) BUT THE WORST IS THE CASE OF APHASIA (HE TOLD US THAT WE MAYBE TALK TO HER BUT DOESN’T UNDERSTAND US, THIS WAS THE WORST THING I COULD HEAR…MY SISTER HAS NO COMMUNICATION PROBLEMS, SHE CAN WALK AND COMMUNICATE…THE PROBLEM IS THE SEIZURES…

AS I SAW GRACE HAS DONE HEMISPHERECTOMY AND I WOULD LIKE TO ASK YOU IF SHE HAD REMOVED THE WHOLE HEMISPHERE OR A PART OF IT…FURTHERMORE THE DOCTOR TOLD US SOMETHING ABOUT ANOTHER DRUG RITUXIMAB, HAVE YOU EVER TRIED IT?

SORRY FOR THE MANY QUESTIONS,

ME AND MY FAMILY, WE WOULD LIKE TO THANK YOU FOR WHAT YOU HAVE DONE,

WE WISH YOU THE BEST,

MANY KISSES TO GRACE.

This e-mail highlights many of the issues that families face in countries where there are not hospitals with the experience necessary to treat rasmussen’s.  The e-mail also mentions rituximab and we continue to receive inquiries about this drug.  Rituximab is used to treat certain cancers and auto-immune diseases.  Its use in rasmussen’s is not well documented, but it does seem to help some individuals for a period of time, but it is not a cure.  For more information on rituximab I refer individuals to our facebook page where families have discussed its use.  Here was a recent post:

“We are hoping to get some advice from you for the use of rituximab and how often should it be administered? Should it be every 6 months, it has been 6 1/2 months now since our daughters last treatment and her doctor has suggested monthly blood tests to confirm the return of her B cells. However we don’t really understand why we should wait for them to return. Have you heard of it being done like this? I remember seeing on the Internet once a boy being the 2nd person in the US to use rituximab for RE. It stated it was used every 6 months for the first 3 years and then yearly. Do you know much about his story and how he is today?”

We recently hired a new research coordinator, Thabiso Chirwa.  Thabiso is working at UCLA under the guidance of Drs. Gary Mathern and Carol Kruse.  We are continuing our research program that is focused on developing a virtual brain and biological repository for rasmussen’s tissue.  Next week we will be shipping tissue from a hemispherectomy being performed on the east coast to UCLA for use in its research devoted to understanding RE.  If you know of an upcoming surgery for RE, please contact me regardless of where you are located.  We have shipped tissue from all over the world.  Yale University has initiated its second round of genetic sequencing of RE tissue and we are expecting initial results in a month or so.  We will keep you posted in future blogs.

I would like to note the excellent work that the Brain Recovery Project is doing regarding the development of rehabilitative protocols following hemispherectomy surgery.  Their research addresses the physical, emotional, and mental aspects of the recovery process.  Please check out their website.

Please continue to support our efforts by donating today.  We are making a difference, but we need your support if we are to continue with our mission.

Walking the High Line in New York City

Viewing the Impressionist Exhibit at the Metropolitan Museum of Art

Lifting Grace fundraiser event for RE Children's Project with Coach Rob Trifone

We recently received some coverage in the press for our donation to UCLA.  The story was picked up Huffington Post Live who agreed to a 20 minute segment devoted to rasmussen’s and the research we are sponsoring at UCLA.  Grace appeared in the segment live via the internet.

We also received coverage in the ALN Magazine,  “Momentum Builds in Quest to Find Cure for Childhood Brain Disease.”  Article below.

We also heard from Dr. Cotsapas at Yale that they are initiating the genetic sequencing on the family trios that we have collected over the last six months.  We are expecting initial results later this spring.  Keep you posted.

I also received an intermediary report from UCLA on their initial research findings.  It is scientific reports, but if you are interested in reading it please let me know and I will forward it.

For one night last weekend, we focused on finding a cure for rasmussen’s encephalitis by bringing together friends, family, and community.  It was a great night.  Grace was surrounded by many of the people who have been so instrumental in getting us through our journey with RE.  Supporting our efforts that night were our researcher partners Dr. Gary Mathern, UCLA; Dr. Chris Cotsapis, Yale, and Joe Voros, our Research Coordinator at Johns Hopkins.  The room was packed with 275 people and the highlight of the evening was when we played this video, TLIP III Video. which was followed by a terrific speech by Dr. Mathern.  Please watch the video, you will need a QuickTime player to open the file.  If you cannot open the file, try this link.

This past week we funded two major research projects totaling $185,000.  One funding to UCLA is the second leg of a research project focused on identifying the underlying mechanisms of RE and the other funding was to Yale to research the possible genetic causes of RE.  We cannot continue to fund these types of projects without your support as well as the support of our hometown, Darien, CT at our annual fundraiser.  Thank you to everyone who made it possible!  Please continue to support our efforts.  We are making a difference.

From left to right, Drs. Gary Mathern and Chris Cotsapas, Joe Voros

Event Chairs Karen Dunn and Jill Walker, thank you!!

In one week we will be holding our annual fundraiser at the Woodway Country Club in Darien, CT.  If you are interested in attending there are still some tickets available.  If you cannot attend please show your support by clicking here and let us know you support our cause.  Any amount is welcomed and appreciated.  Pull the trigger, make a difference now!  Thank you.

Amazing Grace!

For ticket information contact Karen Dunn; kmdunnct@gmail.com

Overview

The mission of the RE Children’s Project is to find a cure for Rasmussen’s encephalitis (RE).  RE is a rare disease and relatively little is known about its cause or the mechanisms that contribute to its characteristic seizures and progressive destruction of one half of the patient’s brain.

Since our founding in 2010 we have:

• Sponsored two research symposiums devoted to RE
• Raised funds for research projects
• Established a consortium of researchers with an interest in RE
• Connected with and supported individuals and families impacted by RE
• Established a mechanism to coordinate the transfer of RE tissue to interested researchers.
• Funded high impact research projects

The first step in our strategy to find a cure was to spark the interest of the medical research community.  This was achieved at our Building New Pathways conference at Deer Valley in October 2010, which attracted 55 of the world’s leading neurology, genetics, and neuroimmunology experts and helped set the direction for our work.

Following the 2010 conference, we implemented a multipronged approach to studying RE.  With a small research budget we funded five high value research projects.  Our goal is to advance and broaden research interest into RE by providing ‘seed capital’ funding that enables researchers to collect and analyze data in preparation for research submissions to larger funding entities.  The projects we fund are vetted and selected by a group of researchers and clinicians with extensive experience in RE research.

To date, we have funded projects to develop animal and cellular models of RE, a genetic ‘trio’ study of patients and their parents, and inflammation protein analysis studies. These projects are designed to identify possible causes that lead to brain inflammation, and will help identify treatments for RE and spare patients from having to undergo a surgical hemispherectomy (removal or disconnection of the affected brain hemisphere), which is currently the only effective long-term treatment for RE.

One of our key activities is the collection of tissue from RE patients (and DNA material from both patients and family members) and the dissemination of this material to interested researchers.  It is a feature of rare disease research that the availability of tissue drives the research interest in the disease.  Without RE tissue there can be no meaningful advance in research.  With only a few hundred reported cases worldwide, the collection of tissue is a difficult but a vital undertaking.

Current activities

Tissue and DNA collection

During this past year we have established a mechanism and protocols for the collection of RE tissue from around the globe immediately following hemispherectomy surgery.  Once the tissue is resected it is shipped for arrival within 24 hours to our research partners at UCLA and Johns Hopkins, who immediately confirm the diagnosis of Rasmussen’s encephalitis before approving the tissue for research purposes.

We are ahead of our tissue collection schedule, thanks to the combination of an expanded social media presence (including our website, Facebook, Twitter, and Linked-In) and our contacts at the major surgical institutions around the globe.  To date we have shipped tissue from Brazil, Spain, and Australia, as well as sites in the US.  In the coming year we are eager to increase the pace of our global transfers.

A major accomplishment during the past year has been the collection of DNA tissue from 25 separate families impacted by RE.  This task reflects the RE Children’s Project’s insistence on research collaboration and cooperation as a way forward to advance research into the disease.  DNA tissue is now being shared by a number of global institutions that have all signed on to a program of collaboration.  With the DNA of a mother, father, and child impacted by RE we are now able to perform genetic analysis to see if there is a genetic component to the disease.

Research funding to date

To date, the RE Children’s Project has provided the following funding for research projects and activities:

UCLA                                             $110,000            Animal Model/Etiology

Yale University                                $25,000       Genetics

University of Montreal                   $50,000      Animal Model

Johns Hopkins Medical Center          $70,000     Research Coordinator

UCSF                                                    $25,000       Infectious Disease

University Hospital Muenster            $50,000    Immunology

The University of California, Los Angeles (UCLA) group is working on correlating the genetic components of RE with clinical, microscopic and imaging data.  Drs. Gary Mathern, Geoffrey Owens, Carol Kruse and Carlos Cepeda have developed specific protocols to model RE disease in an animal model and within a cell culture system.  The models utilize cells (neuroglial cells, neural stem cells, brain infiltrating lymphocytes) obtained from the brain tissue, blood and cerebral spinal fluid (CSF) of RE patients.  The cell culture system will utilize cells taken from RE patients in order to create an environment mimicking the human brain. These cultures will be placed on microelectrode arrays to study RE seizure activity and immune response at a cellular level.  The animal model will employ cells taken from RE patients injected into immune-deficient mice to study seizure activity utilizing video and EEG.   Additionally, tissue from these mice will be removed in order to see the effects of RE on brain tissue.   Dr. Carlos Cepeda at UCLA is working on the role of connexins in inflammation and brain immune defense.  Connexins are proteins that help brain cells to communicate with each other and regulate the cell environment. Another project involves determining if there is evidence for somatic mutations in the brains of RE patients that may set up an anti-inflammatory response if the mutated gene produces a protein seen as abnormal and foreign.  This is being performed in collaboration with Dr. Joe Gleeson at UCSD.

The Johns Hopkins’ group, led by Drs. Adam Hartman, Patti Vining and Carlos Pardo, is working on a project to examine the role that cytokines and chemokines play in RE pathology.  Cytokines and chemokines are specific proteins that function as cellular messengers and influence immune responses.  An advanced Luminex multiplexed analysis will be utilized to study these proteins in samples of brain tissue, blood and cerebral spinal fluid (CSF) obtained from RE patients.  Additionally, gene array analysis will further identify genes linked to brain inflammation and degeneration.

The Yale group, led by Dr. Chris Cotsapas is studying the DNA from RE patient trios (mother-father-affected offspring).  This type of genetic correlation study is only possible with the use of closely related family members that would inherit large portions of DNA.  This study will look for DNA variation that causes the disease. The coding portion of each participant’s genome will be sequenced to look for new or inherited alterations that only occur in affected individuals and thus must cause RE.

The Montreal group, led by Dr. Lionel Carmant, is working on an animal model to study the RE disease state. This model utilizes T-cells derived from RE patient’s blood injected into immune-deficient mice to study seizure activity utilizing video and EEG.  The group’s previous experiments have demonstrated seizure activity 28 days following injection.  Development of an animal model of RE would provide an experimental platform to conduct pre-clinical trials of various anti-inflammatory medications already FDA approved for other diseases, such as multiple sclerosis.

Planned activities in 2013

In 2013, we expect to provide additional research funding as follows:

UCLA                                             $110,000            Animal Model/Etiology

UCLA                                               $75,000           RE Investigator

Yale University                              $50,000          Genetics

Other expenditures on the horizon include a Deer Valley II Conference patterned after our first Deer Valley conference in 2010.  This first very successful conference cost $125,000.  Deer Valley II will be a smaller and focused conference with a more limited participation.

Ongoing research expenditure includes shipment charges for tissue transfer, which range from $500 to $1500 per transfer.  These transfers are our lifeblood and we are hopeful that these expenditures will increase with our continued outreach programs.

Our intermediate goal is to increase our research budget from around $250,000-$300,000 per year to $500,000 within three years.  There is no shortage of projects to fund as we have successfully elevated the global discourse concerning RE.

Longer- term goals

A loftier goal, first mentioned in our Roadmap to a Cure report in 2011, is the initiation of drug trials to determine if an existing drug can be successful as a non-invasive treatment for the disease.  Due to the dispersed distribution of RE patients around the globe and the difficulty in diagnosing the disease, this would be an extremely costly project.

Within the next year we hope to attract additional researchers by reversing the shipment process from the virtual brain bank we are creating amongst our research partners to outside investigators.

As we enter the New Year we wish one another the best and are thankful for our health and the health of our kids.  For too many families they cannot share in these good spirits as they are enveloped in the nightmare of rasmussen’s.  The said truth about rasmussen’s is that we are still in the very early innings about our understanding of this disease and we need to do a lot more if we are to erase the despair of this devastating condition.

Here is an e-mail I received this week from Morocco.  The names are changed to protect privacy.

I an in touch with Amina to learn more of  this situation and we will keep you apprised as we decide how best to help this desperate family.  We are considering a global appeal for funds and will keep you posted.  Please check the blog for updates.

Here is another e-mail we received from Australia this week that addresses an alternative treatment for rasmussen’s.  “We saw Dr Stephen Malone, whom I believe you both know, at the hospital the other day and he said to let you both know what we have been trying with our 10 year old daughter Sarah for her RE. For the last 6 months we have been giving her 4000mg of heat mediated curcumin daily, as we found this was the minimum therapeutic dose in the research given its efficacy for a broad range of anti inflammatory actions. For example, Chronic and complex autoimmune diseases, currently treated palliatively with immunosuppressives, require multi-targeted therapy for greater effectiveness. The naturally occurring polyphenol curcumin has emerged as a powerful “nutraceutical” that interacts with multiple targets to regress diseases safely and inexpensively. Up to 8 g/day of curcumin for 18 months was non-toxic to humans. However, curcumin’s utility is limited by its aqueous insolubility.  We have demonstrated a heat-mediated 12-fold increase in curcumin’s aqueous solubility…..we suggest that the multifaceted heat-solubilized curcumin can ameliorate autoimmune disorders. Heat-solubilized curry spice curcumin inhibits antibody–antigen interaction in in vitro studies: A possible therapy to alleviate autoimmune disorders.”

Molecular Nutrition & Food Research Volume 54, Issue 8, pages 1202–1209, August 2010

Unfortunately, rasmussen’s is not aware of the calendar and we are not resting as we continue to fight for a cure for rasmussen’s encephalitis.

Grace gets the "salon treatment" during a year-end break with good friends in Vermont.