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The Five Senses: Input & Response
This funding opportunity was open to investigations on any aspect of human sensory systems or systems enabling sensory perception in human health or disease. Although traditional sensory systems (sight, sound, smell, taste, and touch) gather, organize, and integrate external stimuli, proposals for internal sensory systems (vestibular, spatial orientation, pain, and others) were also welcome.
Proposals could address but were not limited to sense functionality, injury, disease states, treatment, mitigation, social and societal impacts, or public policy. Examples include human health-related issues such as, but not limited to, the following:
- Physiology or mechanistic aspects of sensory reception or perception;
- Innate or acquired impairments of any sensory reception or perception system:
- age-related changes
- inborn or acquired physical impediments
- illness or treatment-related effects
- New therapeutics, e.g., drugs, mechanical aids, gene & cell based therapies, etc.;
- Impacts on individuals/families/society, e.g., social isolation, depression, ostracization, mental health issues, etc.;
- Legal/public policy aspects, e.g., ADA, accessibility of public buildings, etc.
As deficits in sensory reception or perception may affect several systems simultaneously, e.g., vision and hearing, proposals describing the formation of interdisciplinary teams to address multi-sensory integration projects were also welcome.
This RFA was intended to offer applicants opportunities to conduct important translational research across a wide range of topics.
Proposals addressing healthcare disparities and/or health equity or that focused on or actively recruit underserved, understudied, or special populations, and impacts across the lifespan were encouraged.
This was an open call for proposals. Any investigator with an innovative idea related to the purpose of this RFA was welcome to apply.
Areas of inquiry had to focus on translational research and human health. Proposals requiring the use of nonhuman samples/models were only considered if there was a clear and direct link to subsequent investigations of human health. Proposals investigating basic research questions or those solely limited to pre-clinical applications were not considered.
- Up to $50,000 per award
Principal Investigator: Lora Bankova, MD, Brigham and Women’s Hospital
The sudden loss of smell and taste are among the defining features of COVID-19 that set it apart from other viral respiratory syndromes. SARS-COV2, the virus causing COVID-19, infects nasal epithelial cells including those surrounding the olfactory receptor neurons, the specialized cells responsible for detecting odors altering their sensory function. Importantly, smell and taste disturbances persist in 2-4% of patients 6 months after recovery from COVID-19 and up to 45% of patients recover only partially. Whether the persistent post-COVID smell disruption is linked to long lasting damage to olfactory epithelial cells is unexplored.
We identified a specific type of nasal epithelial cells responsible for the generation and transport of nasal fluid from the nasal glands as the major target of SARS-CoV2. Thus, we hypothesized that disruption of olfactory lining fluid composition might drive the persistent smell distortions associated with COVID-19. To test this hypothesis, we collected clinical characteristics of 214 subjects with post-COVID smell and taste disruptions through an online survey. Nasal dryness was associated with loss of smell and taste in 52% of subjects. We then collected nasal fluid and nasal mucosal scrapings from the lower and upper nasal mucosa from 40 of those subjects, along with objective assessment of smell and taste.
Here, we propose to characterize the protein and lipid mediator composition of the nasal lining fluid from subjects with persistent post-COVID distortion of the sense of smell and taste, define the changes in gene expression in the nasal mucosa and correlate them to the degree of smell and taste impairment.
Our findings will help to explain the causes of persistent loss of smell and taste in patients who have otherwise recovered from COVID-19.
Principal Investigator: Paulo Bispo, PhD, Massachusetts Eye & Ear
Uveitis is a serious inflammation of the internal parts of the eye. It is a costly and debilitating disease for working-age individuals resulting in significant socioeconomic impact, and believed to account for 10-15% of all cases of legal blindness in US. When the cause of the inflammation is correctly determined, uveitis is usually a treatable disease. However, there are a wide range of possible causes including infection, autoimmune diseases, trauma, and cancer. Patients affected by each of these causes can present with overlapping clinical features, introducing many challenges to the diagnostic process.
Up to 60% of uveitis cases are associated with an infection, and a large variety of microbes are involved. Detecting all of these microbes using the current and outdated methods employed in clinical laboratories is time-consuming and inefficient. As a result, patients are treated for weeks or months using therapies selected solely on the basis of an educated guess, an approach that does not work for everyone.
The proposed project capitalizes on the advantages of novel technologies that allow us to rapidly sequence entire genomes to create an all-in-one diagnostic test that would be able to detect ANY microbe in a patient sample. This will significantly reduce the time to diagnose and will provide actionable results for treatment decisions in hours instead of days or weeks.
Our innovative test is also expected to substantially improve diagnostic sensitivity, meaning that more patients will have a correct diagnosis and will be treated accordingly at early stages of the disease.
Principal Investigator: Divya Chari, MD, Massachusetts Eye & Ear
Patients presenting with recurrent episodic vertigo (dizziness) such as Meniere’s disease (MD) and vestibular migraine (VM) can present a diagnostic challenge as they can both produce symptoms of recurrent vertigo, tinnitus, motion intolerance, and hearing loss. Current diagnostic criteria are based on patient history with little contribution from objective measures.
Recently, vestibular perceptual threshold testing has been shown to have the potential to differentiate different types of vestibular dysfunction.Vestibular perceptual thresholds refer to the smallest appreciable stimulus detected by the participant in various rotations and translations of movement.
We hypothesize that use of these novel vestibular perceptual threshold measurements will result in greater diagnostic power than currently available vestibular test modalities.
Principal Investigator: Zheng-Yi Chen, D.Phil, Massachusetts Eye & Ear
Hearing loss is one of the most common forms of sensory deficits without pharmaceutical treatment. The most common cause of hearing loss is the damage to and the loss of the inner ear hair cells, the sensory cells that detect sounds. The mammalian inner ear lacks the capacity to regenerate hair cells and hearing loss is generally permanent.
We have recently discovered that by co-activating two key factors, Myc and Notch1, mature mouse inner ear can re-gain the capacity to undergo cell division and to regenerate hair cells that are functional. Based on the study we have screened for molecules that could lead to hair cell regeneration so the molecules could serve as drug candidates for potential clinical application.
We have identified a group of molecules (the cocktail) that are potent to induce hair cell regeneration in the cultured inner ear. In the proposal we will test the hypothesis that the cocktail is sufficient to regenerate hair cells in the damaged mouse inner ear in vivo. We will further test if and the extent to which hearing can be rescued by the regenerated hair cells.
Success of the project will open up an new avenue using hair cell regeneration to rescue hearing with important clinical implications.
Principal Investigator: Clas Linnman, PhD, Spaulding Rehabilitation Center
Ringing in the ears, or tinnitus, is experienced by one in ten Americans. Tinnitus is similar to phantom limb pain after amputation in that both “phantoms” are thought to arise by how the brain responds to a lack of neuronal signals.
Our brain combines all our senses to form a coherent experience of the world, but we typically rely most on our vision. In mirror box therapy, a mirror is placed so as to create a visual illusion of an intact limb in amputees. The patient “sees” the missing limb, and the illusion allows re-interpreting the lack of sensory nerve signals. This can reduce the phantom pain.
We have applied the mirror box idea to instead treat tinnitus. This is done using a pair of headphones that flip left and right sounds, so sounds at the left are heard as if they are on the right, and vice versa. The effect is that one has to rely completely vision rather than on sound to localize where a sound is coming from. We call this Auditory Mirror Therapy (AMT). In a pilot study, using the device briefly significantly reduced tinnitus awareness and tinnitus handicap in a pilot trial of 20 tinnitus patients.
Here we seek to verify AMT in a larger study of persons with tinnitus, and also control for placebo effects. If AMT indeed works better than placebo, this presents a new treatment option that is non-invasive, safe, affordable and easy to use, with the potential to help many with tinnitus.
Principal Investigator: Samuel Mathias, PhD, Boston Children’s Hospital
Presbycusis is another name for age-related hearing loss, an extremely common condition that primarily affects older people. Presbycusis runs in families, but we know little about the specific genetic factors involved.
Recent studies suggest that people with early onset presbycusis (EOP), defined as occurring between 40 and 65 years old, may carry rare genetic factors that predispose them to develop the condition. The children of people with EOP, having inherited the same genetic factors, have a higher-than-normal risk of developing presbycusis themselves in later life.
This pilot study has two aims.
First, we aim to recruit EOP patients and examine their genomes in order to identify rare genetic variants in hearing/deafness genes.
Second, we aim to recruit the offspring of these patients, as well as age- and sex-matched controls with no family history of presbycusis.
We will compare auditory function between offspring and controls in order to discover the pre-clinical features, or “early warning signs” of presbycusis.
Principal Investigator: James Naples, MD, Beth Israel Deaconess Medical Center
Dizziness accounts for a large number of visits to the Emergency Department (ED) each year. Yet, the available tests we have to diagnose the cause of dizziness in the ED are limited. This is because dizziness is a complex disorder that requires our brain to process information from our eyes/vision, ears/vestibular system, and feet/proprioception. A problem with any one of these systems can make people “dizzy.” And the number of tests necessary to evaluate these systems is large.
Despite these challenges, most sources of dizziness are related to a problem of the ear (otologic) or the brain (central vestibular system). However, making that distinction is difficult based on the patient’s history. In this research proposal, we aim to simplify the approach to diagnosis of dizziness and introduce novel ear-specific biomarkers, prestin and otoloin-1, as a tool to differentiate ear-related (otologic) dizziness from brain-related (central) dizziness.
We will draw blood from patients in the ED and evaluate it for prestin and otolin-1. Following their visit to the ED, patients will be referred to the Otolaryngologist (ENT) for routine evaluation. This ENT evaluation will use confirmatory outpatient testing to help identify the source of dizziness and produce 2 cohorts of patients:
1) ear-related/peripheral or
2) central dizziness.
The biomarkers that were drawn will then be evaluated between the cohorts.
We hypothesize that biomarkers will be different in patients with ear-related dizziness compared to central dizziness.
This novel approach has potential to offer a simple approach to improve diagnosis of a complicated symptoms.
Principal Investigator: Katherine Reinshagen, MD, Massachusetts Eye & Ear
Noise-induced cochlear synaptopathy (CS), also known as hidden hearing loss, is a recent development in hearing research and is thought to account for a large number of patients with hearing symptoms such as ringing in the ear, difficulty hearing in noisy environments, and sensation of fullness in the ears. It is thought that these patients are at risk for developing disabling hearing loss in the future.
Currently, it is considered hidden as it is undetectable by standard hearing tests and imaging. These patients are thought to be potential targets for new, experimental therapies including regeneration of hearing connections in the ear in an effort to prevent clinically detectable, disabling hearing loss.
Advanced diffusion magnetic resonance imaging (MRI) techniques are able to non-invasively detect and measure changes in the brain. Our project seeks to use advanced diffusion MRI to further our understanding of the hearing pathway in the brain and to reliably detect CS-patients at risk for developing disabling hearing loss.
This information could help to find the right patients who may benefit from new treatments directed at CS and hearing loss.
The scientific abstract for this grant award has not been published at the request of the Principal Investigator.
Principal Investigator: Lucy Shen, MD, Massachusetts Eye & Ear
Glaucoma is a disease of the optic nerve and the number one cause of permanent vision loss and blindness in the world. Current treatment options for glaucoma only lower eye pressure and cannot stop vision loss in some patients. This means there are other causes of glaucoma.
We recently discovered that the small blood vessels in the optic nerve of the eye are not working well in patients with glaucoma compared to healthy people. Furthermore, the small blood vessels in the fingers of glaucoma patients are also sick, suggesting that glaucoma is a disease affecting the blood vessels not only in the eye but also in the whole body. We believe that the reason for these sick blood vessels in the body is genetics. Several genes can increase the risk of glaucoma, and 4 of them also affect blood vessels.
In this study, we will use the patient’s genetic information to measure the variation of these 4 genes affecting blood vessels. Based on this, we will assess the connection between the risk from genes and blood vessel problems in the optic nerve and in the fingers of patients with glaucoma. We hope to show that some patients are losing vision from glaucoma due to sick blood vessels, and this is caused by their genetic make-up.
This study will help us to find new ways to treat glaucoma by targeting the blood vessels and the genes that control them.
Principal Investigator: Lana Vasung, MD PhD, Boston Children’s Hospital
The relevance of the signals from the environment for fetal brain development has been widely accepted. Deprivation of signals from the environment leads to altered patterning of the brain.
In contrast to environmental signals, it remains unknown whether and how stimuli arising within the body itself (proprioception) affect fetal brain development.
Impaired or altered proprioception is associated with a number of congenital conditions that fall into the category of non-syndromic isolated musculoskeletal structural birth defects of the face or body (niMSBDs). Despite an increased risk of neurodevelopmental disabilities and despite being among the leading causes of years of pediatric potential life lost whether fetuses with these niMSBDs have abnormal fetal brain development remains a critical knowledge gap.
Our overarching hypothesis is that structural brain development is altered in congenital niMSBDs and this proposal aims to identify the altered regions.
We propose to leverage an existing fetal magnetic resonance imaging (MRI) cohort from the Advanced Maternal-Fetal Care Center at Boston Children’s Hospital and to analyze it using state-of-the-art MRI tools to characterize the fetal brain.
This project will lay the foundation for later characterization of the neural substrate of impaired neurodevelopmental outcome in niMSBDs.