More recently, research applications using small interfering RNA, or siRNA, continue to advance gene therapy’s potential use to modulate the expression of genes, including silencing or suppressing overactive genes. Sanchez-Ramos said, it primarily involved replacing a missing gene or delivering therapeutic molecules to help enhance cell survival. Gene therapy is not new to HD or other neurodegenerative diseases.
Research suggests that the greater the number of C-A-G repeats the earlier symptoms tend to appear and the faster they progress.
The disease emerges slowly, usually between ages 30 and 50 (average age of diagnosis in the United States is 38), but onset can be earlier or later. HD is autosomal dominant, meaning if one parent has a copy of the faulty gene each child’s chance of inheriting the disease is 50 percent. The defective gene leads to a toxic huntingtin protein, which appears to play a critical role in nerve cell function. The normal huntingtin gene contains a DNA alphabet that repeats the letters C-A-G as many as 26 times, but people who develop HD have an excessive number of these consecutive C-A-G triplet repeats - greater than 39. Gene-silencing technology without neurosurgery “It could have applications for modifying a wide range of brain disorders,” Dr. There is still much work to be done but, if proven successful, the nose-to-brain approach could be used to non-invasively (via nasal spray or drops) deliver all kinds of drugs, including DNA therapy and nerve growth factors, which would otherwise be blocked from entering the brain by the blood-brain barrier. “We want all parts of the brain to be exposed to these gene silencing molecules, because Huntington’s is a global brain disease as the disease advances, no part of the brain is spared”. Sanchez-Ramos, professor of neurology and director of the Huntington’s Disease Center of Excellence at the USF Health Morsani College of Medicine. “This NIH study will allow us to test exactly how the nanoparticles get from the nose to the brain, how they are disseminated from the olfactory bulb to other parts of the brain, and how long they stay before dissipating,” said Dr. Delivering therapeutic molecules for a global brain disease Sanchez-Ramos comments on the nose-to-brain nanocarrier delivery system his team will be studying and refining. Not pictured are Neil Aronin, MD, and Anastasia Khvorova, PhD, both of the University of Massachusetts RNA Therapeutics Institute.ĭr. Sanchez-Ramos Vasyl Sava, PhD Xiaoyuan Kong Subhra Mohapatra, PhD Shijiie Song, MD and Shyam Mohapatra, PhD. The interdisciplinary team includes researchers from the USF Department of Neurology, USF Nanomedicine Research Center, Moffitt Cancer Center and the University of Massachusetts Medical School’s RNA Therapeutics Institute.įrom left, the USF team of investigators includes Gary Martinez, PhD (Moffitt Cancer Center) Dr. Sanchez-Ramos and his team - using a mouse model for Huntington’s disease - will assess and refine a new nanoparticle carrier system they’ve designed to transport therapeutic gene-silencing molecules from the nasal passages to the brain. The pledge he made early in his career got a major boost last month when USF Health was awarded a new five-year, $2.3 million grant from the National Institutes of Health’s National Institute of Neurological Disorders and Stroke. They answered with a typical Venezuelan gesture, “¿Y la cura?’” Dr. While celebrating the gene’s discovery with other clinicians in a village, he asked some HD patients gathered why they were not applauding the breakthrough.
At the time, he was a clinical team member of the U.S.-Venezuela Collaborative Research Project, a landmark study that identified and documented cases of HD and the disease’s progression in a unique community of families in Lake Maracaibo, Venezuela. When the single lethal gene for HD was discovered in 1993, USF Health neurologist Juan-Sanchez, MD, PhD, promised some patients he would help find a cure or effective treatment for the rare, but ravaging, disease that runs in families. Sanchez-Ramos talk about a major obstacle to gene therapy. Juan Sanchez-Ramos, professor of neurology at the USF Health Morsani College of Medicine, is the lead investigator for a new $2.3-million NIH grant studying a non-invasive drug delivery system designed to safely and effectively transport large therapeutic molecules (nucleic acids) from nose to brain.