Research

Syner-G Clinical Trial

There is clinical trial being conducted at University of Minnesota where the ketogenic diet is combined with a medicine called miglustat/Zavesca.  Unfortunately, this regimen is not considered a cure.  The regimen may only slow the course of GM1 for certain patients.  It is thought to possibly be effective for certain genetic mutations or only Juvenile patients or those with residual enzyme activity.  Please refer to the description on the clinical trials web site.

Auburn University Gene Therapy Research

Dr. Doug Martin is one of the leading GM1 researchers in the world, researching gene therapy techniques in collaboration with UMass, Lysogene and the Tay-Sachs Gene Therapy Consortium.  Please see this video on Auburn’s research and Auburn’s web site.

UMass Research

At this time, we are raising funds to support GM1 gene therapy research at the UMass Medical School.  Please see the information below for a description of the primary researcher and the research.

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Background

Dr. Sena-Esteves earned his Ph.D. from the University of Porto in Portugal and completed his postdoctoral training in the Department of Neurology at the Children’s Hospital of Philadelphia. In 2004 he became an Assistant Professor of Neurology at the Massachusetts General Hospital and Harvard Medical School. He moved to the University of Massachusetts Medical School in 2009 where he is an Associate Professor in the Department of Neurology and member of the Gene Therapy Center where his laboratory is located. He is also the Program Director of the Tay-Sachs Gene Therapy Consortium. He received the 2011 Outstanding New Investigator Award from the American Society of Gene & Cell Therapy (ASGCT) in recognition of his many contributions to the field of gene and cell therapy.

Research

GM1 gangliosidosis, Tay-Sachs and other diseases like it are essentially recycling problems. Your cells need to recycle materials all the time, a complex process involving many different proteins and enzymes. When one of them is missing, as in GM1, a lipid — or fat — begins to accumulate in the brain. This accumulation leads to a massive die-off of neurons, and persistent degeneration. In other recycling diseases, regular injections of the missing enzyme work well, but in GM1 gangliosidosis and Tay-Sachs disease, in which it is the brain that is mainly affected, the usual injections cannot get past the blood-brain barrier. So the question is, how do we get around the blood-brain barrier?

The major focus of our laboratory is investigating gene therapy approaches for the treatment of neurodegenerative diseases including lysosomal storage diseases, namely GM1-gangliosidosis and GM2-gangliosidoses (Tay-Sachs and Sandhoff diseases); getting across the blood-brain barrier to deliver treatment. We have devised new ways to deliver therapeutic levels of the missing enzymes to the entire brain by injection of adeno-associated virus (AAV) vectors into specific structures in the central nervous system. This means we are adding in a good version of the gene that is mutated in the disease by way of a virus infection. What the virus will do is infect neurons. The virus enters the neuron, and brings in the genetic material you want. And the genetic material is going to tell the neuron, ‘Okay, you start making these normal proteins.’ It’s not gene correction, its gene supplementation — you’re supplementing the cells with a normal gene so the cells know how to make the normal protein. Preclinical studies in animals demonstrated a remarkable extension in lifespan from 8 months in untreated GM1 cats to greater than 4.5 years in AAV-treated cats, with dramatic improvements in quality of life. Based on our exceptional results in animal models, we have begun the studies necessary to move towards human clinical trials for the treatment of GM1-gangliosidosis and Tay-Sachs disease. Ongoing work is on developing second-generation gene therapy approaches for these disease using less invasive approaches such as a simple injection into the bloodstream, or the cerebral spinal fluid via a spinal tap done commonly in most medical centers and has very low risk to patients. The work involves designing new AAV vectors that cross the blood brain barrier and spread throughout the brain more efficiently than existing ones.