A Cure for ‘Orphan Diseases’
In pediatric neurology, many diseases are caused by absent or mutated genes. The genomic revolution has allowed scientists to sequence the genome of every patient, identifying the cause of the problem. But knowing the cause isn’t enough; doctors have to be able to treat it. Unfortunately, rare neurological diseases are often overlooked, leaving a significant gap in research and treatment. These conditions are called “orphan diseases” because there’s no one to look out for them.
Researchers at the UT Southwestern gene therapy center are working to end this problem. Pediatric neurologist Dr. Berge Minassian and molecular biologist Dr. Steven Gray are investigating ultra-rare deadly brain diseases that are caused by a missing gene, and treating patients with a clinical-grade virus that replaces the missing gene. Their research could lead to therapeutic advances for common, complex diseases in which multiple genes are affected.
There are 30-million people in the U.S. suffering from rare diseases. Half of them are kids, and many develop normally until symptoms strike. A pair of pioneering researchers at UT Southwestern have a plan in place to reverse the sobering effects of terminal illnesses through gene therapy.
“It takes a certain spirit to want dive into something in the very cutting edge of medicine, and that pioneering spirit is very strong here in Dallas.”
An experiential, cutting-edge treatment for genetic diseases, gene therapy allows scientists to delete, edit, or replace genes. The treatment has already shown promise in treating diseases affecting organs such as the heart, liver, and spine. The brain, however, offers a more complex challenge and is a relatively unexplored realm of gene therapy. UT Southwestern is changing that through a series of clinical trials for rare neurological diseases, led by Dr. Minassian and Dr. Gray.
Joining UT Southwestern to head the gene therapy center at the Peter O’Donnell Jr. Brain Institute, Dr. Minassian was well versed in diagnosing patients, organizing families, and leading the clinical side, but he sought a scientific partner to complement his expertise and advance his research. He recruited Dr. Gray, “a rising star in his field,” Dr. Minassian says. An Associate Professor of Pediatrics and Molecular Biology, Dr. Gray works with UT Southwestern’s Eugene McDermott Center for Human Growth and Development and the Hamon Center for Regenerative Science and Medicine.
Dr. Minassian and Dr. Gray study fatal, perplexing brain disorders that manifest as problems with vision, speech, and motor function. They work with families whose children have conditions such as giant axonal neuropathy, or GAN, a rare disease that effects the nerves of the body, or Batten disease, a condition that progressively takes away eyesight and mobility. Despite the different diseases, the families’ stories are similar: They initially received evaluations from multiple doctors, only to be told that their child has a fatal disease with little effort being done to find a cure. Instead of giving up, they connected with other families in their position, and they eventually made their way to UT Southwestern, where Dr. Minassian and Dr. Gray offer the first sign of hope.
“Gene therapy really has the potential to transform the way medicine is done. Traditional medicine’s approach is to design a pill that the patient takes for the rest of his or her life. In gene therapy and gene editing, after one injection, the problem is fixed permanently.”
Virus Vector Recipe
UT Southwestern’s gene therapy center is among the few facilities in the country that manufactures a special gene-delivering virus for clinical trials. The virus acts like a delivery truck to bring missing genes into a patient’s cells to correct diseases.
Penetrating the Blood-Brain Barrier
Through a series of clinical trials, the team is developing treatments for more than two dozen rare neurological diseases caused by a missing single gene. They’re using the adeno-associated virus (AAV), a harmless virus that can bypass the blood-brain barrier to deliver the missing gene. Two tablespoons containing trillions of viral particles are loaded into a syringe and injected into the patient’s spinal fluid, which enables the virus to reach the brain and safely supply the genes to neurons and other cells. Through continued research, scientists hope to increase the number of cells that receive the gene, which is currently just a fraction of brain cells.
It’s something few centers in the country can do. It’s costly to produce these clinical-grade viruses, and it requires the expertise of scientists who can do it efficiently and responsibly. UT Southwestern is addressing a lack of accessibility to the virus that has led to a significant bottleneck in the field and, through this work, is getting treatments to children as quickly as possible.
“These are viruses that are very expensive to produce because they need to be of human grade. They have to be ultra-pure, so you need a very special and rather expensive facility, and there’s only a few of them across the country. We are building one of the best ones right here.”
For the families whose children are affected by single-gene defect disorders of the brain, the work of Dr. Minassian and Dr. Gray is revolutionary. But the implications go well beyond this relatively small portion of the population. Success with this therapy could lay the foundation for treating more complex gene editing of common brain conditions, such as epilepsy, autism, schizophrenia, and multiple sclerosis, which involve multiple genes that are either mutated or missing. “We’ll work on the simpler version – the single gene defect disorders of pediatric neurology – to help kids with devastating diseases,” says Dr. Minassian. “In the process, we’ll learn how to do this and be able to scale it up to diseases where multiple genes are affected.”
Support from this mission comes from the families of the children with brain diseases, as they organize bake sales, charity runs, and galas to raise money for research. It also comes from individuals who believe in their pioneering research and its potential to cure all brain disorders. Dr. Minassian and Dr. Gray hope you consider joining them to help us reach a new era of gene therapy.
Making it Happen
Our efforts today and in the near future have the power to make history—transforming how we treat genetic disorders for which there have been no treatments until now. This tremendous effort requires equally ambitious philanthropic leadership and investment to spur on our momentum in gene therapy research and treatment.