Capita Foundation
News and Information for Capita Foundation
Friday, June 23, 2023
Sunday, February 5, 2023
Announcing 2022 Capita Foundation Auditory Research (CFAR) grant award recipients
This research aims to summarize the current state and geographic variation of ear and hearing care (EHC); specifically, we will survey providers globally to assess the availability of infrastructure, including equipment, materials, and ancillary services necessary to deliver care, facilitate training and educational opportunities, and overcome barriers to ear and hearing care service (EHC) delivery. EHC providers include the multidisciplinary care team of ENTs (Ear, Nose and Throat Surgeons), audiologists, audiology technicians, ENT clinical officers, hearing healthcare workers (village healthcare workers trained in ear and hearing care), speech and language therapists, teachers of the deaf and primary health care professionals with specific audiology training. This is a complementary study to ongoing global otolaryngology head and neck surgery (OHNS) and audiology workforce studies which aim to capture the quantity and distribution of OHNS and audiology providers in each country. Taken together, these studies serve as a baseline needs assessment for audiology capacity on an international level, providing novel data needed to inform interventions and policies. These international studies have been developed by members of the Global OHNS Initiative, an international collaborative of over 250 care providers, trainees, and students from over 35 countries. This team has fostered discussion and mentorship across institutional and national boundaries. Beyond the discrete research outputs from this study, this study will facilitate research skill development for trainees who may otherwise have limited opportunities for research involvement and mentorship through their own institutions.
Vestibular Migraine (VM) patients present with auditory symptoms such as aural pressure, tinnitus, and sudden sensorineural hearing loss. Half of Meniere’s Disease (MD) patients present with migrainous features, such as a headache with photophobia or positive family history of migraine. Moreover, about a quarter of VM and MD patients meet both diagnostic criteria. So far, the MD’s pathophysiology remains unknown. Nevertheless, depending on post-mortem temporal bone analyses, endolymphatic hydrops (EH) was noted as a potential MD marker. Current migraine treatment options have shown success in treating some of the patients with MD. In MD when medical treatment fails, the recommendation is to use a second-line treatment, such as the intratympanic injection of steroids. A third-line treatment could be either endolymphatic sac surgery or the intratympanic injection of gentamicin, which has a higher risk of hearing loss. The very last option is destructive surgical treatment labyrinthectomy, with or without cochlear implantation. Since VM and MD overlap, in a nitroglycerin-induced animal model of migraine, we may encounter endolymphatic hydrops experimentally and try to reverse the effect of NTG with migraine treatment. If our hypothesis is true; intractable Meniere’s disease’s treatment options would change and there would be no more destructive treatment methods like labyrinthectomy or intratympanic gentamicin injections and it could be treated conservatively.
Friday, January 7, 2022
Announcing 2021 Capita Foundation Auditory Research (CFAR) grant award recipients
Brian M. McDermott Jr., Ph.D.
Hair cells are the cellular receptors for sound that
reside in the inner ear. These cells are the epitome of cellular
specialization to accomplish a specific biological task:
mechanotransduction—the conversion of mechanical stimuli into an electrical
response. These cells contain specific organelles on which hearing is
dependent, including the stereocilia. The mechanosensitive hair bundle consists
of a precise arrangement of actin-based stereocilia, which extend from the hair
cell's apical surface. A systematic increase in stereociliary length results in
a bevel-shaped hair bundle. Each cylindrical stereocilium is stiff, but its
uniform girth tapers towards the base to allow for flexion. When sound enters
the ear, it causes these tiny stereocilia to vibrate at high rates. Damage to
the stereocilia is often the cause of hearing impairment. The damage can be
caused by either loud noise or genetic mutations. In this grant, we will
explore the self-healing capacity of the hair bundle and examine how it may be
used for therapeutic approaches.
Vibhuti Agrahari, Ph.D.
Cisplatin-Induced Ototoxicity (CIO) and associated hearing loss is irreversible and there are no treatments currently available to reverse CIO, therefore, prophylactic care is critical. However, to reduce CIO, there is a need to identify the appropriate route of drug administration, and selection of an optimal drug delivery strategy with enhanced therapeutic efficacy, and the product translation to clinical application. This project will investigate the development of novel targeted nanoformulations to provide a prophylactic cure of CIO not only in adults but also in pediatric patients. The bio-responsive nanoformulations (Nano-SensoGel) will be designed to provide a long-term therapeutic effect through enhanced bio-retention and inner ear targeted attributes of the delivery system. The outcomes of this study will be critical in addressing the clinical needs towards the development of inner ear targeted technologies for the prevention of CIO-induced hearing loss.
Announcing 2020 Capita Foundation Auditory Research (CFAR) grant award recipients
Alessia Paglialonga, Ph.D.
National Research Council of Italy (CNR); Institute of Electronics, Information
Engineering and Telecommunications (IEIIT), Milan, Italy
Project WHISPER will develop and evaluate a novel, web-based system to support widespread screening and prevention of hearing impairment. It will be the first system to combine: (1) remote speech recognition testing using an automated, language-independent speech-in-noise test, (2) assessment of the risk factors for developing hearing impairment via a language-independent, icon-based interface, and (3) modeling of the individual risk for developing hearing impairment and the associated cognitive decline using explainable artificial intelligence (AI). The project will help answer the need to increase access to screening and prevention (for older adults, for individuals in underserved areas, for minorities, and for those with low socioeconomic status). It will develop tools that are language-independent and natively designed to be delivered at a distance, e.g. via web or mobile app, and natively integrated with explainable AI to extract actionable knowledge from the measured data.
Currently gene therapy using adeno-associated viral vectors (AAV) has been successful in small mammals, but nearly 80% of all genes that are affected in genetic forms of hearing loss are too large to fit into AAV vectors found in humans. Thus, there is an unmet need for the development of alternative gene-delivery tools in the translational development of gene therapy for congenital hearing loss. Successful completion of the aims in this proposal will provide a foundational understanding of Magnetic Nanoparticle (MNP) behavior in small animal models and accrue preclinical data to support the translational development of MNP technology for inner ear gene delivery. Leveraging this team’s experience in successfully bringing other inner ear therapeutics from the bench top to the bedside, we intend to similarly advance the translational development of MNPs into nonhuman primates and ultimately human clinical trials.
Mridula Sharma, Ph.D.
1. To assess and understand the mechanisms underlying speech perception in an innovative and more ecologically valid manner by using EEG and novel signal processing methods.
2. To delineate the effects of age on processing and understanding natural speech in noise.
3. To identify neural indices that could be used, in future clinical studies, as clinical measure of an individual’s ability to understand speech in the real world.
The outcomes will significantly advance knowledge in our understanding of the auditory processes that are required for older adults to understand natural speech. By including a clinical test population, the proposed project will provide the knowledge required for future development of clinical management protocols and strategies using speech tracking, thereby ensuring future clinical translation of the project outcomes.
The
figure that shows the analysis from our pilot data |
Soroush Sadeghi, M.D., Ph.D.
The general aim of my research is to reach a better understanding of vestibular signaling and its modulation following compensation or adaptation and to find practical ways for enhancing vestibular compensation in humans. This can be specifically useful for patients (e.g., after therapeutic vestibular neurectomy) or in conditions where unusual adaptation is required (e.g., space travel).
Figure 1 |
In recent years, the traditional notion that peripheral end organs (i.e., hair cells and afferent terminals) in the inner ear are mere sensors has been challenged due to the presence of feedback (via an efferent pathway) from central areas. It has been shown that efferent inputs can modulate the activity of hair cells and afferents in vitro. The funding from Capita Foundation will be used to study the effect of the GABAergic and cholinergic efferent pathways on the response properties of the vestibular pathway. Using an in vivo mouse model, we will use a method developed in our lab for intralabyrinthine injection (Fig. 1A) of different agonists and antagonists of relevant receptors and ionic channels and evaluate their effect on the vestibular nerve response by measuring the vestibular sensory evoked potentials (VsEP) (Fig. 1B). To find the behavioral correlate of the observed neuronal changes, we will measure the effect of intralabyrinthine injections of these drugs on the vestibulo-ocular reflex (VOR) – a reflex that functions to stabilize the eyes during head movements (Fig. 2).
Figure 2. Recording the VOR response in mice. Eye
movements will be recorded with an infrared camera in a head-restrained mouse.
The mouse is rotated in the horizontal plane at different frequencies and
velocities in the dark. Right panel
traces shows example eye movements during VOR response to head rotation. Figure 2
Thursday, November 26, 2020
Capita Foundation funding acknowledged in PLOS ONE research article
LoCHAid: An ultra-low-cost hearing aid for age-related hearing loss
Article published by: Soham Sinha, Urvaksh D. Irani, Vinaya Manchaiah and M. Saad Bhamla
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238922
Saad Bhamla, Ph.D.
Thursday, March 21, 2019
Announcing 2019 Capita Foundation Auditory Research (CFAR) grant award recipients
Prof. Karen Avraham
Tel Aviv University
Project Title: "Gene therapy in a mouse model of human hearing loss DFNB76"
Adeno-associated virus (AAV) has become very popular in the gene therapy field in recent years, and several proof-of-principal studies in the field of hearing loss have demonstrated its potential for treatment of genetic deafness. AAV has major advantages for gene therapy. Most importantly, AAV appears to elicit no immunological response in humans and recombinant AAV is also almost entirely incapable of integration, which enhances its safety. Several synthetic AAVs have been engineered to transduce cells in the inner ear with high efficiency and have been used to demonstrate rescue of auditory and vestibular function in deafness mouse models. We hope our efforts will lay the groundwork for future development of gene therapy in humans. In addition, we hope this work will contribute to the understanding of the roles of nesprin proteins in cellular processes in general, and specifically in outer hair cell physiology.
The point of no return? These outer hair cells are in excellent form, arranged in three rows, just a day before they start deteriorating due to an absence of the gene SYNE4. Alterations in the DNA sequence of the SYNE4 gene leads to deafness in children and adults. Models are being used to test methods of gene therapy, in order to rescue hearing due to defects in the SYNE4 gene.
Credit: Shahar Taiber, MD-PhD student
Karen Avraham - Genomics of Deafness laboratory, Tel Aviv University
Valeriy Shafiro, Ph.D.
Rush University
Villanova University
Project Title: "Improving speech recognition for listeners with auditory neuropathy"
University of Ottawa
Project Title: “Investigating the Temporal Resolution Capacity in School Aged Children via Neurophysiological Measurement. Pilot Study.”
Prof. Koravand's research deals with the relationship between the peripheral and central auditory systems in children. Her goal is to develop neurophysiological measures (biological markers) to assess the central auditory functions of children during early childhood, to prevent disorders while brain plasticity is still significant.
Wednesday, February 6, 2019
Daniel
A. Llano, M.D., Ph.D.
In our research program, we will examine the impact of aging on the auditory system. We will focus on developing innovative approaches to measure metabolic changes in the aging auditory system and developing novel interventions to mitigate them. Successful completion of this work will lead to new approaches to preserve hearing as we age.
Josée Lagacé, Ph.D. and Benoît Jutras , Ph.D.
University of OttawaProject Title: "Virtual Reality For Auditory Training Therapy: A Pilot Study"
Virtual reality (VR) allows an individual to interact in real time with a three-dimensional, computer-simulated environment. The objective of this pilot study is to evaluate VR as an effective interface for ensuring uptake and motivation to auditory training in children with auditory processing difficulties. Since many children with auditory processing difficulties also have learning problems at school, this approach could also contribute to the enhancement of their learning experience and as well as to a reduction of schooling failure.
Madhu Sundarrajan, Ph.D.
University of the PacificProject Title: “Audiological and Communication Outcomes in Children with Unilateral Hearing Loss: A Pilot Study.”
Unilateral hearing loss (UHL) or single-sided deafness is a type of hearing impairment where individuals have typical hearing in one ear and impaired hearing in the other ear. Permanent UHL exists when the average pure tone air conduction threshold at 0.5, 1, and 2 kHz is greater than or equal to 20 dB HL or pure tone air conduction thresholds are greater than 25 dB HL at two or more frequencies above 2 kHz in the affected ear with an average pure tone air conduction threshold in the good ear less than or equal to 15 dB (National Workshop on Mild and Unilateral Hearing Loss 2005). It is estimated that 1/3 of children with hearing loss are diagnosewith UHL (Lieu, 2018).
Matthew J. Wilson, Ph.D.
Northern Illinois University
Philippe Vincent, Ph.D.
Johns Hopkins School of MedicineProject jointly funded with Hearing Health Foundation
https://hearinghealthfoundation.org/
Project Title: “Investigating mechanisms of degeneration of ribbon synapses between auditory inner hair cells and type 1 afferent nerve fibers after noise trauma in mammals.”
During all of our life, we are surrounded by sounds that include different frequencies and intensity levels. In the inner ear, the sensory hair cells pick up the sound signal and transmit it to auditory nerve fibers via chemical synapses by releasing the transmitter glutamate; and auditory nerve fibers transmit the sound-coding signal to the brain.
Sound intensity is encoded by the amount of glutamate released by the hair cell, leading to glutamate receptor activation and then action potential firing in auditory nerve fibers. During noise exposure, it has been described that auditory nerve fiber endings can be damaged short- or long-term, most likely due to and excess of calcium influx into the auditory nerve fiber endings. This phenomenon is called excitotoxicity, however, the underlying mechanisms are not completely understood.