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The age of human gene therapy has at last begun in earnest. This new era presents both tremendous opportunities and hope for our patients, but also brings unprecedented challenges, as accelerated discoveries and expensive new treatments are creating new clinical, political and ethical challenges.

I’ll share some USF Health research efforts to advance gene therapy for neurological diseases – but, first, some context.

Following the discovery of the structure of DNA in the 1950s, medical researchers predicted we would soon decipher the molecular mechanisms of hereditary diseases, enabling us to then genetically engineer treatments for those disorders shortly thereafter.  Although progress over the next several decades was far slower than anticipated, the launch of the Human Genome Project in 1990 made that future seem imminent.

However, in the late 1990s, the tragic death of a young patient volunteer (due to a systemic reaction to an adenovirus vector), along with a series of technical and clinical trial failures made effective gene therapy again seem like a distant dream.  Nevertheless, progress resumed in the mid-2000s and technological advances finally translated into effective clinical treatments over the ensuing decade.

In 2018, the FDA issued its first approval for a true in vivo gene therapy of a hereditary disorder (hereditary retinal dystrophy), and another for hereditary transthyretin amyloidosis, both of which are devastating diseases with no truly effective previous treatments.  These approvals were quickly followed by several more, including treatments and a possible cure for hereditary spinal muscular atrophy (SMA), a progressive and fatal paralyzing disease of infants and children.

Over the last year, a host of new therapies entered the pipeline for testing and FDA consideration. Many have shown robust and often dramatic Phase 2 and 3 evidence of efficacy.

Several USF Health Morsani College of Medicine (MCOM) researchers are on the front lines of these studies:

• Juan Sanchez-Ramos, MD, PhD, director of the USF Health Huntington’s Disease (HD) Center, received a $2 million NIH grant to develop and test a smart nanoparticle delivery system for placing gene therapies more precisely (and noninvasively) into areas of the brain affected by HD. He is also now launching an antisense oligonucleotide gene therapy study in HD patients. HD results from a triplicate repeat gene mutation, which mutates the huntingtin protein into a toxic form; this new therapy blocks production of the mutant protein, slowing or even arresting the disease.
• Theresa Zesiewicz, MD, director of the USF Health Ataxia Research Center, is working with a group of industry partners to develop gene therapy strategies for Friedreich’s ataxia (another triplicate repeat disorder).
• Tuan Vu, MD, director of the USF Health ALS Center, is exploring potential human studies of a gene therapy for one of the most common forms of hereditary amyotrophic lateral sclerosis (SOD1 ALS), in collaboration with the company that just secured FDA approval for its SMA gene therapy.
• Bob Hauser, MD, director of the USF Health Center for Parkinson Disease (PD) and Movement Disorders, is collaborating with a pharma company on genetic modulation of the production of alpha-synuclein (a pivotal protein in the pathogenesis of PD) in animal models, and to consider how this might be adapted as a therapy for human PD.

Many other outstanding MCOM translational and clinical researchers are now also entering this rapidly expanding arena.

With these advances and many more to come, this modern era of gene therapy continues to build excitement.  However, scientific progress has been so rapid that the world’s health systems are struggling to keep up with the integration and adoption of these new technologies. In particular, the cost of targeted gene therapies can impede their widespread use in clinical practice; pharmaceutical companies have priced many of these new therapies (some of which may actually be lifetime cures), at the multimillion dollar mark for each patient treated.

Beyond gene therapy, new genetic engineering technologies have profound implications for humankind. The world’s scientific, ethical and governmental bodies are now striving to quickly define where the boundaries of this technology should be, and grappling with when and how to discourage premature human experimentation in sensitive areas.

As controversy in other areas where science and politics intersect has demonstrated, surmounting these challenges together as a worldwide community may, in the end, be the ultimate hurdle to overcome as we enter the brave new world of gene therapy.

Clifton L. Gooch, MD
Professor and Chair, Department of Neurology
USF Health Morsani College of Medicine

USF Health Neuroscience Institute leaders accompany U.S. Rep. Gus Bilirakis on a tour of research laboratories in the Byrd Alzheimer’s Center, a centerpiece of the Institute.

Neurological diseases are growing at an unprecedented rate as Americans live longer and survive other chronic conditions like cardiovascular disease and cancer.

During U.S. Rep. Gus Bilirakis’ visit to the USF Health Neuroscience Institute on Aug. 24, the congressman was given an overview of the multidisciplinary research and clinical care that the University of South Florida conducts to help combat the human and economic burden of neurological diseases, including dementia, stroke, Parkinson’s disease and brain trauma.

The USF Health Neuroscience Institute, home of the Johnnie B. Byrd, Sr., Alzheimer’s Center, integrates three clinical departments — Neurology, Neurosurgery and Psychiatry – along with related basic and translational science departments. The Institute’s focus on consolidating disease-specific care for a wide spectrum of neurological diseases is intended to strengthen collaborative neuroscience research across USF and help accelerate promising discoveries from bench to bedside.

Laura Blair, PhD, assistant professor of molecular medicine, explains her team’s research on chaperone proteins that drive different states of the tau protein associated with Alzheimer’s and other neurodegenerative diseases. The USF Health researchers are identifying promising targets to help slow or prevent disease progression.

Bilirakis toured laboratories and the Johnnie B. Byrd, Sr., Alzheimer’s Center, the centerpiece of the Neuroscience Institute, with Stephen Liggett, MD, associate vice president for research at USF Health; Clifton Gooch, MD, chair of neurology at the USF Health Morsani College of Medicine (MCOM); and Glenn Currier, MD, chair of psychiatry and behavioral neurosciences at MCOM.  He also met with Robert Hauser, MD, director of the USF Parkinson’s Disease and Movement Disorders Center, which is designated a National Parkinson’s Foundation Center of Excellence.

These USF Health leaders spoke about the need for more federal resources directed toward helping advance early diagnosis and new treatments to delay, minimize and prevent nervous system disorders.

Robert Hauser, MD, (left) director of the nationally recognized USF Parkinson’s Disease and Movement Center, welcomes Bilirakis.

Among a few informational items they shared with the congressman:

• National Institute of Health grant funding does not cover the expense of high-tech equipment increasingly needed to do things like study single cells in the brain to understand the root cause of neurological diseases.
• 100 million Americans are afflicted with at least one neurological disease. A USF study led by Dr. Gooch and published last year in the Annals of Neurology found that the cost of diagnosed neurological disorders approaches a staggering $800 billion a year.
• More than half of MCOM’s $14.7 million in clinical trial revenue for FY 2018 was neuroscience related (neurology, psychiatry and neurosurgery).
• In addition to the Byrd Alzheimer’s Center and Parkinson’s Disease and Movement Disorders Center, other centers of excellence under the auspices of the USF Health Neuroscience Institute include stroke, epilepsy, multiple sclerosis (MS), Huntington’s disease, amyotrophic lateral sclerosis (ALS), ataxias with an emphasis on Friedreich’s ataxia, and aging and brain repair.
• USF Health Psychiatry and Behavioral Sciences continues to strengthen neurobiology research to discover new treatments for Alzheimer’s disease and abnormal brain development, as well as related mental disorders including autism. Current NIH-funded projects include studying ways to effectively deliver central nervous system drugs across the blood-brain barrier and testing the effectiveness of computer brain training games in protecting against cognitive decline.

USF Health’s Stephen Liggett, MD, (right) chats with Bilirakis in one of the laboratories at the Neuroscience Institute.

From left: Stephen Liggett, MD, USF Health associate vice president for research and Morsani College of Medicine vice dean for research; Congressman Gus Bilirakis, who represents Florida’s 12th District; Clifton Gooch, MD, chair of neurology; and Glenn Currier, MD, chair of psychiatry and behavioral neurosciences.

-Photos by Eric Younghans, USF Health Communications and Marketing

University of South Florida  study shows research investment critical to prevent destabilizing economic impact

TAMPA, FL (March 29, 2017) — More Americans are living longer and surviving chronic conditions like heart disease and cancer. Ironically, this triumph is also leading to a drastic rise in neurological disorders, which disproportionately attack the elderly.

Clifton Gooch, MD, professor and chair of the Department of Neurology at the University of South Florida Morsani College of Medicine in Tampa, is the lead author of study that details the enormous cost of neurological diseases to the nation.  The study is reported in the Annals of Neurology, the official journal of the American Neurological Association and the Child Neurology Society.

Clifton Gooch, MD

Working with USF College of Public Health colleagues Etienne Pracht, PhD, and Amy Borenstein, PhD, Dr. Gooch looked at the nine most prevalent and costly diagnosed neurological disorders and found the annual cost is staggering, totaling nearly $800 billion. By 2030, $600 billion will be spent treating stroke and dementia alone.  In addition, low back pain, traumatic brain injury, migraine headache, epilepsy, multiple sclerosis, spinal cord injury and Parkinson’s disease emerged as the most common disorders posing a serious financial burden.

“Given these extraordinary and rapidly growing costs, a concrete strategy is urgently needed to reduce the burden of neurological disease,” he said.

In the paper, Dr. Gooch calls on the federal government to provide more NIH funding to speed the development of treatments and cures for diseases such as dementia and stroke, including therapies to delay, minimize and prevent them. He also proposes the creation of a more effective national database to track treatment successes and failures.

“The very future of the neurological sciences and the patients we serve is now at stake, and the welfare of generations yet to come hangs upon the success of our efforts.”

Dr. Gooch writes that the years of productivity lost in the 100 million Americans living with neurological and musculoskeletal disorders is more than any other category of disease.

-USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. The University of South Florida, established in 1956 and located in Tampa, is a high-impact, global research university dedicated to student success. USF is ranked in the Top 30 nationally for research expenditures among public universities, according to the National Science Foundation. For more information, visit www.health.usf.edu

Media contact:
Tina Meketa, University Communications and Marketing
tmeketa@usf.edu or (813)955-2593