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.
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.