One community’s effort to control genetic disease

A field action report published by the Clinic in the American Journal of Public Health (AJPH)

Drs. Strauss, Puffenberger, and Morton were recently published in the American Journal of Public Health, outlining the Clinic’s unique model of care and the financial outcomes for the communities we serve. Dr. Strauss surmises, “Systems of medical care that allow clinicians and molecular biologists to work side-by-side at the appropriate scale, concerned foremost with the care of patients, are a means to ensure that affordable gene-based methods become a sustainable force in medical practice. Critics who argue that social and cultural factors dictate what represents ‘appropriate technology’ in any particular setting should remember that persons born with serious genetic lesions are victims of chance and should have preferential claim to the practical benefits of scientific progress.”

Visit the AJPH website or download the report.

From bedside to bench and back again

In collaboration with Dr. Peter Crino of the University of Pennsylvania and graduate students like Whitney Parker, the Clinic continues to make progress on devastating diseases like Pretzel Syndrome. Below, Whitney highlights her unique research experience, a great example of moving from the clinical bedside to the laboratory bench. We all hope that these collaborative efforts lead back again to the bedside with life-saving treatments.

From Whitney Parker, graduate student at the University of Pennsylvania: Last fall, a few of my colleagues and I joined the families and staff members of the Clinic for Special Children for the Pretzel Syndrome picnic. Dorothy Brubaker and her family welcomed us to their home, where we were immediately greeted with warm welcomes and all the delicious food we could manage to eat (and then several desserts after that)! Sitting with families at the picnic, I recognized that not only was everyone there an expert in the experience of and treatments for Pretzel Syndrome, but also they had an overwhelming sense of community and desire to help their children and others. I was amazed that families from Wisconsin and New York had traveled to Lancaster County to join us for this event as well! After lunch, Dr. Strauss talked to everybody about the outcomes of treating Pretzel Syndrome patients with rapamycin. I described our lab work using rapamycin and a similar new drug (an inhibitor of p70S6kinase, the enzyme directly following mTOR in the disease pathway) to restore movement to abnormally arrested cells in the developing brain in a mouse model of Pretzel Syndrome. Afterward, we asked if any of the Pretzel Syndrome patients or their parents would be willing to donate skin samples in order for us to be able to test the efficacy of the drugs on the movement of human cells. The response was overwhelming! In addition to Dr. Strauss himself, two parents and three Pretzel Syndrome patients volunteered to let us take a biopsy of their skin! Afterward, we all got to ride in a pony cart driven through a recently-flooded stream by the talented Melissa.

When we got back to the lab, we spent the next few days extracting cells called fibroblasts from the skin samples. These are the cells that normally form scars in wound healing, and they can serve as a good experimental model of cell movement. We tested the movement of fibroblasts from Pretzel Syndrome patients compared with movement of those from the parents and Dr. Strauss. Pretzel Syndrome fibroblasts showed decreased movement, compared with the other cells. Our belief is that impaired movement of cells in the developing brain is what contributes in a large part to seizures in Pretzel Syndrome patients. Interestingly, when we treated Pretzel Syndrome fibroblasts with rapamycin or the new drug, movement was restored! We think this is important because it suggests that these drugs can be effective for not only mouse cells but human cells as well, and may be effective in helping to restore normal brain development in patients with Pretzel Syndrome if started early enough. We are also experimenting with different nutrient changes that can affect disease manifestation, with the hope of being able to recommend dietary changes as a supplementary treatment. With the help of a colleague at the University of Michigan, we are in the process of turning some of the Pretzel Syndrome fibroblasts into brain cells, so we can study the process that causes seizures in Pretzel Syndrome and ways to treat this. Overall, the contributions of everybody who donated skin samples have been immensely helpful so far in letting us test different treatment options in human cells.

The experience of meeting families with children affected by Pretzel Syndrome as well as the patients themselves has completely changed my perception of the disease and the work I do in lab. Their sense of community and wanting to do anything to help those who suffer from the disease was incredibly inspiring! After visiting with the Mennonite and Amish families, I no longer think of Pretzel Syndrome as an interesting process to study in the lab purely for the sake of scientific knowledge, but instead as a huge burden to the patients and their loved ones suffering though it. I hope that through learning more about the disease process, we can begin to figure out ways to treat it and help improve the lives of Pretzel Syndrome patients and their families who inspire

Pictured: Induced pluripotent stem cells derived from the skin biopsies volunteered from CSC patients at a Pretzel Syndrome Family picnic in the summer of 2011. Dr. Crino and his team will transform these stem cells into neuronal cells that express the Mennonite STRADA mutation, and can then be used to test the effect of various medications on disease expression in brain cells. Image used with permission by Dr. Crino.

2012 Summer Students at CSC

As part of our ongoing effort to train future scientists and clinicians, the Clinic is hosting a full house of summer students!

From Dr. Puffenberger: “We are grateful to have so many talented, young minds at the Clinic this summer, and we all feel that the investment in such talent is vital to our mission and success.”

Maggie Steinmann—University of California, Davis, Biology
Maggie is studying Congenital Adrenal Hyperplasia (CAH), a condition found in the Amish community as well as the general population.

Alison Greidinger—2012 Eyler Fellow, Franklin & Marshall College, Biology
Alison is working with Dr. Morton on Proprionic Acidemia research, a particularly complicated condition that the Clinic has studied for several years.

Kiri Sunde—2012 Mary Ellen Avery Fellow
Kiri is spending a full year at the Clinic as our very first Avery Fellow, working to complete a handbook for GA1 parents and also new methods of molecular screening.

Orla Houlihan—Children’s Hospital of Philadelphia, trainee
Orla discovered the Clinic during a pulmonary rotation at CHOP and decided to extend her stay in the United States for two additional weeks in order to shadow our doctors. Orla is an Irish physician in training with a particular interest in pediatric genetics.

Becky Willert—2012 Franklin & Marshall graduate in Biology
Becky is spending a full year at the clinic on a novel method of newborn screening for Muscular Dystrophy.

Theresa Swenson, PhD—Elizabethtown High School Teacher
Though not a traditional student, Theresa volunteers her time and expertise to help develop a diagnostic method for GM3 concentrations, a crucial measurement for the fight against GM3 deficiency.