Clinical Trial in Treatment of Fatal Disease

A potential cure for the fatal disease GM1 gangliosidosis, which is nearing clinical trials next year, could one day also be used to treat more commonly known diseases like Alzheimer’s and Parkinson’s.

Dr. Doug Martin, a research scientist with theCVM’s Scott-Ritchey Research Center, says the gene therapy vector developed with collaborators, which is currently being vetted for human clinical trials in 2017, could be a break through for other diseases.

“The technology developed for GM1 treatment could be applied to any number of diseases, like Alzheimer’s, which may turn out to be an unusual form of a storage disease like GM1,” Dr. Martin said. “Our vector could have much broader implications and, theoretically, the same technology used to treat GM1 could also treat Alzheimer’s.”

GM1 gangliosidosis is a lysosomal storage disease that attacks the brain and spinal cord, a progressive and degenerative condition that is always fatal in children.

Dr. Martin, part of a team of researchers in the Tay-Sachs Gene Therapy Consortium, an international collaborative group of scientists committed to searching for a cure, developed and tested the vector based on the adeno-associated virus (AAV). Currently, Lysogene, a France-based clinical stage gene therapy biotechnology company, is developing pre-clinical studies for the vector.

The development of a treatment for GM1 gangliosidosis using AAV gene therapy was initiated in 2005 by Martin, an associate professor in the Department of Anatomy, Physiology and Pharmacology at Auburn, and Dr. Miguel Sena-Esteves, associate professor in the Neurology Department and director of the Gene Therapy Center at the University of Massachusetts Medical School.

GM1 glangliosidosis occurs when the body does not produce enough of a specific enzyme, β-galactosidase (βgal), which recycles molecules from the body. When the molecules build to abnormal levels, they progressively destroy the body’s nervous system. The earlier the onset in children, the quicker the disease kills.

Dr. Sena-Esteves and Dr. Martin re-engineered the virus to introduce the gene that produces βgal. The virus acts as a vessel, its genetic material removed and replaced with a concentrated dose of the βgal gene. Healthy cells pass along βgal, essentially allowing deficient cells to soak in the crucial enzyme.

The experimental therapy has extended the lives of cats, which have a similar genetic defect, from an average of eight months to more than 52 months, with no ill effects and with normal function.

“There is no question now the disease can be treated successfully,” said Dr. Martin. “We have seen how it has worked in cats with the disease and how it is has extended their lives as healthy animals.”

Dr. Martin and a team of researchers have found success in administering the virus two ways: the first, and most successful, is by intracranial injections through the skull, which has succeeded in getting therapy beyond what is called the blood-brain barrier. This option is moving toward clinical trial the fastest, he added.

The second is the development of an IV treatment which provides sufficient doses to the brain through the blood system. “This method is very promising but we have to administer more of the vector to ensure enough of it is in the brain,” he added.

What the researchers need now is funding to move the process along. “Time and money are factors,” said Dr. Martin.

Funding will allow researchers to complete necessary and important regulatory mandates and to perform toxicity and bio-distribution studies in normal mice, both required by the FDA to demonstrate safety of the vector that will be used to treat children.

Hope for the Children

It is what no parent wants to hear: “Your child is dying. There is no cure.”

Ryan and Jenny Bragg of Hoover are the most recent parents to hear that when a physician told them their two-and- a-half-year-old daughter, Clara, has GM1 gangliosidosis.

“It was Aug. 11 and the diagnosis came out of the blue,” said Ryan. “It was a real kick in the gut.”

The Braggs are not alone, as Clara is the second case of GM1 in Alabama. In 2013, Porter Heatherly of Opelika, was diagnosed with GM1. Sadly, Porter, the son of Auburn alumni Sara and Michael Heatherly of Opelika, died of the illness Nov. 10 at the age of 4.

These parents and others have banded together— linked by love for their children and a terrible disease—for a cure. The Heatherlys and Braggs have joined forces with Christine Waggoner and her husband, Doug Dooley, of California to raise awareness of and funding for GM1 research being conducted at the College of Veterinary Medicine.

Cure GM1 was founded by Waggoner and Dooley in honor of their daughter, Iris, who suffers from Juvenile GM1. To date, they have raised more than $960,000, but their goal is to raise enough to get the treatment developed by Dr. Martin and a team of Auburn researchers to clinical trials at the National Institute of Health next year, which will take nearly $2 million.

For the Bragg family and others, the college’s research has become their hope. “Having the diagnosis has been strangely helpful, because, before, we were just spinning our wheels trying to figure out what was going on,” said Jenny Bragg. “Now we have something to work toward even though it’s among the worst diagnoses ever.”

The Braggs, Texas natives, moved to Alabama in 2014 from California through his position at PepsiCo/Frito-Lay. Clara was about 15 months old and, while she was enrolled at a daycare, they noticed that she wasn’t reaching the same developmental level as other children her age.

“We started early intervention by seeing specialists at UAB,” Jenny said. After numerous tests, none giving them a diagnosis, the parents enrolled her in physical therapy. It was another doctor’s appointment that led to an answer. The neurologist recommended that the family enroll in a study through the UAB-HudsonAlpha Center for Genomic Medicine. They soon had an answer.

“We were blessed with the opportunity to enroll in this study and we rejoice in the fact that she is not yet regressing,” Ryan Bragg said.

Within 48 hours of the diagnosis, Ryan Bragg had researched the disease on the internet, learning about the college’s research efforts, and was on the telephone with Dr. Martin. “He was very kind and spoke to me for 45 minutes, providing more information,” Ryan Bragg said.

“That conversation shifted the course for us. The door is not closed and there is hope.”

After talking to Christine Waggoner, the Braggs became more encouraged and have become advocates for curing the disease. “We were spurred into action very quickly, learning as much as we could.”

While they say they are realistic, they believe that Clara could benefit from the clinical trial. “We believe there is a real chance.

“We recognize that time is critical, not just for Clara but for other children carrying the disease,” Jenny Bragg said. And while they are not used to the spotlight, the couple decided to share their story, saying the disease “forced us to act.”

The family has created a website,, and has enlisted family and friends in the fundraising process. “Hopefully, it will make a difference,” she said. “We need so much support.”

“We want people to know that there is a cure that has been found in the laboratory and in animals,” Ryan Bragg said. “The number 1 thing we need is money. We are not going to stop until it is funded; there is not a choice to do otherwise.”

The goal of all three families is to move giving to a larger arena, beyond family and friends to the public at large. “We’ve always been charitable people, giving to many worthwhile organizations,” Ryan Bragg said. “But never once have we been presented with the opportunity that, one day, we could say that a disease has been cured because of our donation.

“Literally two years from now, we might be able to look at this situation and say that,” Ryan Bragg said. “But, more importantly, it would have a profound impact on other parents to never have to hear the words we heard from a doctor.”