BBDF Blog

published September 30, 2009

Team to Focus New Gene Discovery on Developing a Therapy for Batten Disease

Dr. Andrea Ballabio, scientific director of the Telethon Institute of Genetics and Medicine (TIGEM) in Naples, Italy, has joined the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine as a visiting scientist for one year. During that time, Dr. Ballabio’s research project will be based on his discovery of a gene that controls the ability of the cell to degrade and recycle toxic molecules, which was recently published in the journal Science. In particular, his team will focus on testing the application of his discovery for the therapy of Juvenile Neuronal Ceroid Lipofuscinoses, also known as Batten disease, a rare and fatal genetic disorder of the nervous system that begins in childhood.

A $2.5 million gift from the Beyond Batten Disease Foundation and Cherie and Jim Flores enabled the Jan and Dan Duncan Neurological Research Institute to invite Dr. Ballabio and his colleague, Dr. Marco Sardiello, to collaborate on this research specific to Batten disease. The gift is the largest single research award ever made in this disease area. The mission of the Beyond Batten Disease Foundation is to increase awareness and raise research funds for both finding a cure and developing a universal carrier screening test for hundreds of devastating genetic diseases.

“It is a wonderful gift to have Dr. Ballabio working with our team,” said Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. “He is a distinguished scientist whose research epitomizes the mission of this institute.”

Dr. Ballabio, who was previously on the faculty at Baylor College of Medicine in the Department of Molecular and Human Genetics, focuses his studies on the biological mechanisms underlying genetic diseases, using both traditional and genomic approaches, and the development of innovative therapeutic approaches.

In addition to his work with the TIGEM, Dr. Ballabio currently holds the position of professor in medical genetics at the University of Naples Federico II.

“I am very excited to return to Baylor and contribute to the world class research activities at the Jan and Dan Duncan Neurological Research Institute,” said Dr. Ballabio. “This year will give me the opportunity to perform collaborative research projects with outstanding Baylor investigators and to start joint international research and training programs between Baylor, Texas Children’s Hospital, the Neurological Research Institute and TIGEM.”

Previously, Dr. Ballabio was president of the European Society of Human Genetics and is a member of several professional organizations including the European Molecular Biology Organization. He has published over 230 papers in prestigious, international scientific journals and has received numerous national and international awards for research and culture including the European Society of Human Genetics Award and the Silver Medal of the President of Italy. Dr. Ballabio is also the founder and director of the Biology for Medicine Foundation.

About the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital Recognizing there was no single institution using multidisciplinary research to guide the study of pediatric cognitive development and neurological disorders, Texas Children’s Hospital created the Jan and Dan Duncan Neurological Research Institute. Scheduled to open in 2010, the institute will be the first dedicated facility to use a multidisciplinary research approach to rapidly accelerate the search for treatments for pediatric neurological disorders. The specially-designed facility will be the crossroads where more than 170 researchers (over 15 principal investigators and their teams) across disciplines collaborate to bring promising new therapies to those afflicted with neurological diseases.

About Texas Children’s Hospital
Texas Children’s Hospital is committed to a community of healthy children by providing the finest pediatric patient care, education and research. Renowned worldwide for its expertise and breakthrough developments in clinical care and research, Texas Children’s is ranked in the top ten best children’s hospitals by U.S.News & World Report. Texas Children’s also operates the nation’s largest primary pediatric care network, with over 40 offices throughout the greater Houston community. Texas Children’s has embarked on a $1.5 billion expansion, Vision 2010, which includes a neurological research institute, a comprehensive obstetrics facility focusing on high-risk births and a community hospital in suburban West Houston. For more information on Texas Children’s Hospital, visitwww.texaschildrens.org.

http://www.vision2010.texaschildrens.org/newsroom_articles/nri_dr_ballabio_joins_093009.html

In June 2009, the Beyond Batten Disease Foundation co-sponsored the annual Batten Disease research conference held by the NCL-Foundation based in Frankfurt Germany. For a summary of the meeting and the research presented, please visit: http://www.ncl-stiftung.de/englisch/research/ncl_congresses/index.php

Test in Development to Prevent Hundreds of Other Orphan Diseases

Austin, Texas – March 4, 2009 – Leading scientists, medical researchers and affected families joined together today to launch Beyond Batten Disease Foundation, an organization committed to finding a cure for this rare disease that claims the lives of children. The organization is also developing a single, inexpensive blood test to detect the gene mutations for Batten disease and hundreds of other so-called “orphan” diseases.

Beyond Batten Disease Foundation announced its plans at a ceremony with Texas Gov. Rick Perry in conjunction with Rare Disease Day, an annual event that occurs on February 28. Gov. Perry proclaimed February 28 Batten and Rare Disease Day in Texas, urging all Texans to learn more about the special challenges affecting these patients, take advantage of emerging diagnostic tools, and do all they can to combat these afflictions.

“Batten is a tragic disease that robs children of their youth, and eventually, their lives,” said Gov. Perry. “I greatly admire the strength and courage of the families who have united to find a cure. I am pleased that the state of Texas will be the center for an exciting and extensive scientific initiative to someday eradicate this and other rare diseases.”

Craig and Charlotte Benson of Austin, Texas, formed Beyond Batten Disease Foundation after learning that their five-year-old daughter, Christiane, has the disease. After months of testing and inconclusive results, they learned that Batten disease is an inherited, neurodegenerative disorder that affects several hundred children in the United States. Without warning, children with this disease suffer from vision loss and seizures, ultimately impairing the child’s cognitive and motor skills. Today, there is no known treatment or cure for the fatal disease.

“I’ll never forget that day. In a single moment, a disease we had never heard of changed our entire life,” said Charlotte Benson. “As a parent, it’s difficult to imagine a worse fate for your little girl than Batten disease.”

The Foundation plans to accomplish its mission of eradicating Batten disease in two ways: first, by raising awareness and money to accelerate research to find a cure; and second, by preventing Batten disease and hundreds of other rare genetic conditions through the development of a carrier screening test.

“Research is currently underway at prominent institutions in the U.S. and abroad, but because Batten disease is so rare, it is severely underfunded,” said Suzanne Kho, executive director of the foundation. “For many families, this is truly a race against time. Science provides hope for a cure, but we need to raise additional funds for multi-year research programs and clinical trials in order to turn hope into reality.”

The Foundation assembled a board of directors that includes Mark B. Chandler, Ph.D., and Kyle L. Janek, M.D., both of whom have deep experience in the scientific and medical research communities. Faced by the challenges of raising awareness and funding for such a rare disease, they quickly realized an opportunity to broaden their initiative on additional rare diseases.

“For a child to be born with an auntosomal recessive disease, of which Batten disease is one of hundreds, both parents must carry the gene mutation. Because these diseases are so rare, and testing is currently so expensive, few doctors talk to their patients about testing for these gene mutations,” said Chandler, a founding director of Beyond Batten Disease Foundation. “We are working to develop one easy and inexpensive blood test to detect the gene mutations for hundreds of rare diseases. The science is possible today. We just need the support of volunteers and financial donors to make it happen.”

“Another devastating genetic disease of children, called Tay-Sachs, has largely been eradicated through carrier screening. We want to follow that model,” said Craig Benson. “There are hundreds of these conditions that, individually, are very rare. However, when taken as a group they are much more commonplace. It is the Foundation’s goal to make the test a standard of care for all young men and women as part of their routine health screening.”

The Foundation has formed a partnership with the National Center for Genome Resources (NCGR), one of the world’s top genetic screening laboratories, to develop the test. The initial test for approximately 75 diseases will be ready in the fall of 2009.

Please visit www.beyondbatten.org to learn more about Beyond Batten Disease Foundation and get involved by donating money, volunteering your time or spreading the word.

by Sharon Begley
Newsweek Magazine

No child should be born into this world with Batten Disease, which—and here I’ll just quote from the National Institutes of Health—causes “mental impairment, worsening seizures, and progressive loss of sight and motor skills. Eventually, children with Batten disease become blind, bedridden, and demented. Batten disease is often fatal by the late teens or twenties.” And if Mark Chandler has his way, no more will be.

Chandler is chairman and CEO of Biophysical Corp., a pioneering company that, as I wrote about two years ago, offers a battery of tests for “biomarkers” that can indicate the presence of early-stage disease before symptoms appear. (The virtue of testing for biomarkers rather than disease genes is that with the former you are testing for the presence of the actual disease, but with DNA tests you are almost always testing for the possibility of developing a disease in the future.) Now Chandler is hoping to offer tests to identify carriers of rare genetic disorders such as Batten Disease: as carriers, they would not have the disease and so would have no idea they carry silent genes for it until, tragically, their child is born with one of these 1-in-a-million disorders. A genetic test could warn them.

The model is what the Ashkenazi Jewish community has done, beginning in 1969, to screen couples for Tay-Sachs disease, which was more common among that population than Americans generally. If both a husband and wife carried the rare mutation, they were counseled to avoid having children, or (if they had not yet married) even to find other partners, since if two carriers mate their children have a 25 percent chance of having the disease. As a result of the widespread screening, Tay-Sachs has been almost eliminated in American Jewry; of the 20 or so children born with Tay-Sachs in the U.S. each year, most are from Louisiana’s Cajun community or are French-Canadians, two population groups that also carry the mutation.

It may seem like overkill to test all couples or would-be couples for diseases that are so rare, but Chandler thinks he can develop a test for the 400 or so “orphan,” diseases such as those on the list of the National Association for Rare Disorders. All are autosomal recessive: if you inherit the mutation from one parent, and therefore have one copy of the disease gene, you do not develop the disease but are a carrier; if you inherit one copy from mom and one from dad because both your parents are carriers, you get the disease. Chandler is confident that new DNA technology can offer the test for all 400 for $125. You can spend more on a maternity dress.

But before the DNA test can be offered, it needs to be validated—that is, known carriers must have their DNA tested, and the screening must correctly identify them as carriers, while not identifying non-carriers as carriers. That is, no false negatives and no false positives—or as near to “no” as one can get, which Chandler believes is 99.9 percent accurate. To validate the test for autosomal recessive orphan diseases, he figures he needs 5 to 10 couples for each disease. If you want to be one of them—volunteering to spare other children these fatal diseases—you can contact Kristin Thomas Miskovsky at kmiskovsky@biophysicalcorp.com, or call her at 512.623.4923.

http://www.blog.newsweek.com/blogs/labnotes/archive/2008/11/17/orphan-diseases-calling-all-volunteers.aspx