Several diseases of the nervous system are progressive and untreatable, robbing humans of their function, their intellect or their mobility. Alzheimers disease is the most common neurodegenerative disorder in the United States and the sixth most common cause of death in the United States, afflicting over five million individuals. This number is rising daily. Despite its prevalence, we lack effective therapies for stopping or slowing degeneration of the disease. What should be the “Golden Years” become the years of challenge and chronic care.

Spinal cord injuries, on the other hand, tend to afflict people at a young age, and result in decades of impaired function and chronic medical illness. Therapies to restore neurological function are lacking.

Dr. Mark Tuszynski is trying to identify useful therapies to have a major impact on these tragic and currently untreatable diseases of the nervous system. He is applying cutting-edge technologies, including gene therapy and stem cell therapy, to disorders such as Alzheimer’s disease, spinal cord injury and ALS. Using gene therapy to deliver potent growth factors to the nervous system, he aims to prevent or reduce cell loss in Alzheimer’s disease and ALS. Using the remarkable biology of neural stem cells, he aims to form new neural connections across sites of severe spinal cord injury to restore function after even chronic injury.  And using the techniques of modern neuroscience, he aims to understand basic mechanisms through which the brain codes for new memories. Findings from some of this work have already moved into human clinical trials, and more potential therapies are in the pipeline for first in human clinical trials in Alzheimer’s disease, ALS and spinal cord injury.

Mark Tuszynski, M.D., Ph.D., is the Director of the Translational Neuroscience Institute at the University of California, San Diego. He is developing and exploiting new technologies to tackle chronic, progressive and untreatable diseases of the nervous system, including Alzheimer’s disease, ALS and spinal cord injury. In the field of Alzheimer’s disease, he is attempting to harness the power of growth factors in the nervous system to prevent cell death and stimulate cell function, thereby reducing progression of the disease and improving memory. To deliver growth factors to the brain, he is employing the technique of gene therapy, aiming to permanently alter brain cells in such a way that they produce the natural proteins that can prevent their degeneration. Dr. Tuszynski was the first person to bring gene therapy to the adult nervous system in human clinical trials, and his translational programs are continuing in Alzheimer’s disease and ALS.  More recently, he has also sought to exploit the remarkable biology of neural stem cells to combat spinal cord injury. When implanted into sites of spinal cord injury, neural stem cells exhibit a startling ability to form many new connections over long distances in the injured spinal cord. He is developing this technology as a potential therapy for spinal cord injury. In a third line of research, Dr. Tuszynski’s research group is attempting to understand how the adult brain encodes new memories and experiences, using skilled motor training in rodents as a model system. It is hoped that his collective research effort, and experience with first in-human clinical trials, will lead to the development of new types of treatments for common and untreatable diseases including Alzheimer’s disease, ALS and spinal cord injury.

1. Alzheimer's Disease, Growth Factors and Gene Therapy: Dr. Tuszynski is developing new therapies that aim to slow the relentless progression of Alzheimer’s disease. His approach is based on the combination of two powerful tools: 1) gene therapy, which has undergone a recent renaissance for the treatment of human disease, and 2) growth factors, which are natural proteins of the brain that potently reduce cell death and stimulate cell function. When growth factors are applied to the brain using techniques of gene therapy in animal models of Alzheimer’s disease, they reduce disease progression and improve learning and memory. Moving this technology forward into the human arena, Dr. Tuszynski led the first human clinical trial of gene therapy in the adult brain, delivering a nervous system growth factor called Nerve Growth Factor (NGF) to patients with Alzheimer’s disease. This program is currently continuing in clinical trials across the country. Another program that may be yet more potent is moving into clinical trials, delivering a growth factor called BDNF (brain derived neurotrophic factor) to memory circuits of the brain in a region called the entorhinal cortex and hippocampus. Dr. Tuszynski is now trying to bring this significant new program to human clinical trials, and needs further funding to take this step.

2. Spinal Cord Injury and Neural Stem Cells: In a unique project aiming to develop new treatments for spinal cord injury, Dr. Tuszynski is exploiting the remarkable biology of neural stem cells in an effort to repair the spinal cord following severe injury. He is taking neural stem cells (including human cells) and placing them into sites of severe spinal cord injury in animal models. He and his colleagues have developed a method for supporting the survival of neural stem cells in sites of spinal cord injury. The transplanted cells send out new “wires” called axons, from the injury, thereby forming new electrical relays across the site of spinal cord injury. The number of axons growing out from transplants of neural stem cells is extraordinary, offering substantial potential for development into a treatment for spinal cord injury. Dr. Tuszynski’s approach differs from other stem cell therapies in a significant way: he and his colleagues are injecting the neural stem cells directly into spinal cord injury site, repopulating the site of injury with neurons in an effort to form new connections across the injury site. Studies performed by other groups, in contrast, inject cells either above or below the sites of injury, or into the spinal fluid or blood; in theory, injecting cells directly into the center of the injury site will result in the formation of many more connections with the potential to restore function. Dr. Tuszynski’s research group is moving on to larger animal testing, both to better understand the basic biology of these fascinating cells, and to pave the way for human clinical trials. Funding is needed to support these important translational studies.

3. Learning and Memory: In this project, Dr. Tuszynski aims to understand how the brain encodes new memories: how does the adult brain learn?  Using animal models of skilled motor learning (or “muscle memory”), he is examining how the architecture of neurons changes when we acquire the ability to perform a new skilled motor function, such as playing a musical instrument or learning how to throw a football to the running back’s “sweet spot” far down the field. How does brain structure adapt in learning these new skills, and how are neural connections modified in the new circuitry that contains the learning? This ambitious work uses tools of molecular biology, neuroanatomy, synaptic physiology and behavior to map out the neural networks that representing the “learning engram” in the brain. This work has implications for training, aging and discovery of new therapies.