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Researchers launch first clinical trial for Wolfram syndrome

Many people with rare genetic disease die prematurely by Jim Dryden•November 10, 2016 The drug dantrolene is a muscle relaxant approved to treat patients with cerebral palsy, multiple sclerosis and muscle spasticity. Recent research also suggests it can prevent the destruction of insulin-secreting beta cells in animal models of Wolfram syndrome. Researchers at Washington University School of Medicine in St. Louis are launching a new clinical trial to assess the safety of a drug treatment for patients with the rare disease Wolfram syndrome. Wolfram syndrome affects about one in every 500,000 people worldwide. Many of those patients die prematurely from the disease. Patients with Wolfram syndrome typically develop diabetes at a very young age and require insulin injections several times each day. The disorder also causes hearing loss, vision problems and difficulty with balance. Although doctors treat patients’ symptoms, there have not been any therapies that slow the syndrome’s progress. However, researchers at Washington University School of Medicine soon will test a drug treatment in 24 patients who have the genetic disorder. The scientists previously reported in the Proceedings of the National Academy of Sciences that the drug, dantrolene — a muscle relaxant approved to treat patients with cerebral palsy, multiple sclerosis and muscle spasticity — prevents the destruction of insulin-secreting beta cells in animal models of Wolfram syndrome and in brain cells differentiated from skin samples taken from patients with the illness. “Nobody has ever tested dantrolene in patients with Wolfram syndrome, so our first and most important objective is to make sure it’s safe,” said principal investigator Fumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine. “I am very hopeful, however. The major question that I get from every patient I [...]

Stem Cell Discovery Might Lead to Fix for Gene Mutation Behind Hereditary Hearing Loss

A new study in STEM CELLS Translational Medicine offers people with genetic hearing loss the promise of a new therapy that just might outperform artificial cochlear implants.  DURHAM, NC (PRWEB) MARCH 31, 2016 A new study in STEM CELLS Translational Medicine offers people with genetic hearing loss the promise of a new therapy that just might outperform artificial cochlear implants. Implants currently are the most effective way to treat sensorineural hearing loss, a type of hereditary hearing loss caused by genetic mutations in the hair cells — the sensory receptors of the auditory system, found in the inner ear (the cochlea). A cochlear implant helps transfer sound to the patient’s hearing nerves and enables them to hear. But many researchers believe that stem cells could offer a more comprehensive and better fix for this problem. “If we can find a way to correct gene mutations using stem cells it might restore the normal function of the hair cells and, thus, the patient’s hearing, too,” said Jin-Fu Wang, Ph.D., a lead investigator on the study conducted with colleagues at Zhejiang University, Shanghai Jiaotong University, Wenzhou Medical University in China, and Cincinnati Children's Hospital Medical Center and Emory University in the United States. In previous studies, induced pluripotent stem cells (iPSCs) derived from human adult somatic tissue such as skin and urinary cells have been generated from patients with ALS, spinal muscular atrophy, diabetes and other diseases for testing potential therapies and to correct disease-specific genes. The Wang team wanted to try this approach for sensorineural hearing loss. They hypothesized that a protein-coding gene called MYO7A plays an important role in the assembly of stereocilia into bundles. (Stereocilia are the part of the hair cells that respond [...]

Army Tests Hearing Drug at the Rifle Range

(The Wall Street Journal via NewsPoints Desk) (Ref: The Wall Street Journal) August 21st, 2015 The Wall Street Journal reported that a trial being conducted in collaboration with the US military is testing an experimental drug that might prevent noise-induced hearing loss. The compound, a liquid form of d-methionine, was developed into a drug by Kathleen Campbell, an audiologist at Southern Illinois University School of Medicine. If eventually cleared by federal regulators, the drug would be the first approved to prevent hearing loss, and could benefit people in the military, as well as people who work in noisy industries. Campbell designed a randomized three-year Phase III study, which began in late 2013 and is expected to enroll up to 600 subjects. Specifically, each soldier gets a hearing test, and then, over 18 days that include stints at the rifle range, drinks a liquid containing either the drug or placebo twice daily. Earlier this year, researchers published the results of a study in Marines of the compound N-acetylcysteine. The trial found no significant effect on overall hearing loss, but there were indications the substance has promise, according to principal investigator Richard Kopke, who hopes to test it in combination with a second compound. Meanwhile, Sound Pharmaceuticals received Defense Department support to run a trial of another compound in soldiers, but the study was never enrolled because of logistics concerns.

Orchestrating hair cell regeneration: a supporting player’s close-up

Jul 16 2015 KANSAS CITY, MO—The older we get, the less likely we are to hear well, as our inner ear sensory hair cells succumb to age or injury. Intriguingly, humans are one-upped by fish here. Similar hair cells in a fish sensory system that dots their bodies and forms the lateral line, by which they discern water movement, are readily regenerated if damage or death occurs. A neuromast sensory structure (green) of the zebrafish lateral line, which helps the fish detect water movement, is shown among surrounding cells (cell nuclei in red). Image: Courtesy of Piotrowski Lab, Stowers Institute for Medical Research A new study in the July 16 online and August 10 print issue of Developmental Cell, from Stowers Institute for Medical Research Associate Investigator Tatjana Piotrowski, Ph.D., zeros in on an important component of this secret weapon in fish: the support cells that surround centrally-located hair cells in each garlic-shaped sensory organ, or neuromast. “We’ve known for some time that fish hair cells regenerate from support cells,” Piotrowski explains, “but it hasn’t been clear if all support cells are capable of this feat, or if subpopulations exist, each with different fates.” While mammals also have support cells, they unfortunately do not respond to hair cell death in the same way. So understanding how zebrafish support cells respond to hair cell loss may provide insight into how mammalian support cells might be coaxed into regenerating hair cells as well. Zebrafish are particularly amenable to studies of regeneration because transparent embryos and larvae render developmental processes visible and experimentally accessible. Piotrowski and her team treated zebrafish larvae with the antibiotic neomycin, which kills hair cells, then monitored support cell proliferation in regenerating neuromasts for [...]

OHSU scientists unlock first critical step toward gene therapy treatment for patients with mitochondrial disease

07/15/15  Portland, Ore. Gene-based cures for human diseases are now on the horizon A study led by Shoukhrat Mitalipov, Ph.D., and Hong Ma, M.D., Ph.D., at the Center for Embryonic Cell and Gene Therapy at Oregon Health & Science University and the Oregon National Primate Research Center has revealed the first critical step in developing novel gene and stem cell therapy treatments for patients with mitochondrial disease. This breakthrough, published online today in the journal Nature, sets the stage for replacing diseased tissue in patients and opens the door to a world of regenerative medicine where doctors are able to treat human diseases that are currently incurable. The scientists successfully used mitochondrial replacement to create an embryonic stem cell with healthy mitochondria from a patient’s skin cell containing mitochondrial DNA mutations. These mutations can cause a vast range of fatal or severely debilitating diseases, including diabetes, deafness, eye disorders, gastrointestinal disorders, heart disease, dementia, and several other neurological diseases. In the United States, 1,000 to 4,000 children are born with mitochondrial DNA disease each year. There are no meaningful treatments or cures. In May 2013, Mitalipov was the first in the world to demonstrate the successful use of somatic cell nuclear transfer to produce human embryonic stem cells from a research subject’s skin cell. That breakthrough followed a six-year chain of discoveries that included his 2007 work demonstrating the nuclear transfer method to create embryonic stem cells from a nonhuman primate. This chain included what may be a new technique to help families prevent inherited mitochondrial disease in future generations. “To families with a loved one born with a mitochondrial disease waiting for a cure, today we can say that a cure is on the horizon. [...]

New findings hint toward reversing hearing loss

July 15, 2015 By Julia Evangelou Strait SUNG-HO HUH PHOTO A normal mouse cochlea shows a characteristic spiral shape. Unlike birds and amphibians, mammals can’t recover lost hearing. In people, the cells of the inner ear responsible for detecting sound and transmitting those signals to the brain form during early stages of development and can’t be replaced if lost due to illness, injury or aging. Studying mice, scientists at Washington University School of Medicine​ in St. Louis have identified two signaling molecules that are required for the proper development of a part of the inner ear called the cochlea. Without both signals, the embryo does not produce enough of the cells that eventually make up the adult cochlea, resulting in a shortened cochlear duct and impaired hearing. The study, available online in the journal eLife, contributes to the understanding of inner ear development, a first step toward the goal of being able to recover lost hearing. “To eventually be able to restore hearing, we would like to be able to regenerate the sensory hair cells of the cochlea,” said senior author David M. Ornitz, MD, PhD, the Alumni Endowed Professor of Developmental Biology. “If the inner ear in birds and fish is damaged, for example, cells in the inner ear are naturally turned back into progenitor cells that are capable of replacing the sensory cells. But mammals are more complex — with a better sense of hearing over a wider range of sounds. However, it is thought that in exchange for better hearing, we have lost the ability to regenerate sensory hair cells.” In the new study, Ornitz and his colleagues showed that proper inner ear development in mice depends on the presence of two [...]

Found: A Likely New Contributor to Age-Related Hearing Loss

New nerve cell connections on sensory cells in mice could be at fault July 13, 2015 FAST FACTS: Hair cells in the inner ear “sense” sound waves and convert them to electrical signals sent via outgoing nerve cells to the brain. With aging, some hair cells die, contributing to hearing loss. New connections between certain hair cells and nerve cells coming from the brain also increase with age. Researchers now suspect these incoming nerve cells could be contributing to hearing loss. Mature hair cells, left, lose connections to outgoing neurons (blue) and gain connections to incoming neurons (red) as they age, right. Paul Fuchs, Johns Hopkins Medicine Conventional wisdom has long blamed age-related hearing loss almost entirely on the death of sensory hair cells in the inner ear, but research from neuroscientists at Johns Hopkins has provided new information about the workings of nerve cells that suggests otherwise. In a paper published July 1 in The Journal of Neuroscience, the Johns Hopkins team says its studies in mice have verified an increased number of connections between certain sensory cells and nerve cells in the inner earof aging mice. Because these connections normally tamp down hearing when an animal is exposed to loud sound, the scientists think these new connections could also be contributing to age-related hearing loss in the mice, and possibly in humans. “The nerve cells that connect to the sensory cells of the inner ear are known to inhibit hearing, and although it’s not yet clear whether that’s their function in older mice, it’s quite likely,” says Paul Fuchs, Ph.D., the John E. Bordley Professor of Otolaryngology–Head and Neck Surgery at the Johns Hopkins University School of Medicine. “If confirmed, our findings give [...]

Is Boston Children’s Hospital on its way to curing genetic deafness?

Jul 8, 2015, 1:08pm EDT Jessica Bartlett Boston Business Journal COURTESY/ POCKAFWYE VIA CREATIVE COMMONS ​Researchers used gene therapy to restore hearing in mice with a genetic form of… more Researchers at Boston Children’s Hospital and Harvard Medical School have used gene therapy to restore hearing in mice with a genetic form of deafness. The work, published today in the journal Science Translational Medicine, is a promising start for restoring hearing in humans that have profound hearing loss caused by genetic defects. “These findings mark a defining moment in the way we understand, and can ultimately challenge, the burden of deafness in humans,” said Ernesto Bertarelli, co-chair of the Bertarelli Foundation, the primary funder of the research, in a release. Scientists used gene therapy in mice that had mutations to the TMC1 gene, which account for 4 to 8 percent of cases in the common causes of genetic deafness. Teams inserted the healthy gene using a virus in two types of mutant mice – one that had the gene TMC1 completely deleted, and another that had a mutation in the TMC1 gene. Using gene therapy on the TMC1 gene, researchers completely restored hearing to the first mouse type, seeing mice jump at the sound of abrupt, loud tones. In the other mouse model, gene therapy in related gene TMC2 was partially successful at restoring hearing. Scientists are optimistic about using the gene therapy in clinical trials, as the virus is already used in human gene therapy for blindness, heart disease, muscular dystrophy and other conditions. But that work is still five to 10 years away. Researchers said they want to optimize the protocol and continue the trials in mice to see if mice retain hearing [...]

VEST helps deaf feel, understand speech

Rice University, Baylor College of Medicine project allows subconscious translation  HOUSTON – (April 8, 2015) – A vest that allows the profoundly deaf to “feel” and understand speech is under development by engineering students and their mentors at Rice University and Baylor College of Medicine. Under the direction of neuroscientist and best-selling author David Eagleman, Rice students are refining a vest with dozens of embedded actuators that vibrate in specific patterns to represent words. The vest responds to input from a phone or tablet app that isolates speech from ambient sound. Eagleman introduced VEST – Versatile Extra-Sensory Transducer – to the world at a TED Conference talk in March. He is director of the Laboratory for Perception and Action at Baylor College of Medicine and an adjunct assistant professor of electrical and computer engineering at Rice, of which he is also an alumnus. His lab studies the complex mechanisms of perception through psychophysical, behavioral and computational approaches as well as neuroscience and the law. The Rice students working on VEST, all electrical and computer engineering majors, call themselves the Eagleman Substitution Project (ESP) team. They include seniors Zihe Huang, Evan Dougal, Eric Kang and Edward Luckett and juniors Abhipray Sahoo and John Yan. They are aiding Scott Novich, a doctoral student in electrical and computer engineering at Rice who works in Eagleman’s lab. Novich devised the algorithm that enables the VEST to “hear” only the human voice and screen out distracting sounds. The low-cost, noninvasive vest collects sounds from a mobile app and converts them into tactile vibration patterns on the user’s torso. Haptic feedback supplants auditory input. The first VEST prototype put together by the team has 24 actuators sewn into the back. A [...]

Gene Therapy May Boost Cochlear Implants

Bioscience Technology, by Lauran Neergaard ~ April 23, 2014 Australian researchers are trying a novel way to boost the power of cochlear implants: They used the technology to beam gene therapy into the ears of deaf animals and found the combination improved hearing. The approach reported Wednesday isn't ready for human testing, but it's part of growing research into ways to let users of cochlear implants experience richer, more normal sound. Normally, microscopic hair cells in a part of the inner ear called the cochlea detect vibrations and convert them to electrical impulses that the brain recognizes as sound. Hearing loss typically occurs as those hair cells are lost, whether from aging, exposure to loud noises or other factors. Cochlear implants substitute for the missing hair cells, sending electrical impulses to directly activate auditory nerves in the brain. They've been implanted in more than 300,000 people. While highly successful, they don't restore hearing to normal, missing out on musical tone, for instance. The idea behind the project: Perhaps a closer connection between the implant and the auditory nerves would improve hearing. Those nerves' bush-like endings can regrow if exposed to nerve-nourishing proteins called neurotrophins. Usually, the hair cells would provide those. Researchers at Australia's University of New South Wales figured out a new way to deliver one of those growth factors. They injected a growth factor-producing gene into the ears of deafened guinea pigs, animals commonly used as a model for human hearing. Then they adapted an electrode from a cochlear implant to beam in a few stronger-than-normal electrical pulses. That made the membranes of nearby cells temporarily permeable, so the gene could slip inside. Those cells began producing the growth factor, which in turn [...]