平特五不中

Neuro Commercialization Grants - Ignite: Funded Projects

Ignite Grants represent the first of two phases in the HBHL Neuro Commercialization Grants program and their objective is to support small-scale validation/proof-of-principle efforts in the development of a neuroscience-related technology.
Read more about this program and the evaluation process.


Funded Projects

Ignite Grants Competition IV

HBHL Research Principal Investigator Project Title Funding Received
1 Antonia Arnaert Development and Testing of a Functional Prototype of an Interactive Augmented-Reality Based Surgical Guidance System for Spine Surgery $50,000
3 Reza Farivar Brain Health Probe $50,000
2 Benoit Gentil Development of a gene therapy for ARSACS and intermediate filament disorders $50,000
4 Gail Myhr Development of a companion research portal for data collection during AVATAR therapy for Auditory Hallucinations using an AVATAR therapy app $50,000

Ignite Grants Competition III

HBHL Research Principal Investigator Project Title Funding Received
4 Jeremy Cooperstock Extending Internet Multimodal Access to Graphical Exploration (IMAGE) $50,000
2 Christopher Pack Non-invasive control of pathological brain activity $49,883
2 Yannis Trakadis A Novel Personalized Treatment Platform $48,300
1 Stefanie Blain-Moraes The Adaptive Reconfiguration Index: A Novel Tool for Prognosticating Recovery in Unresponsive Patients $50,000
3 Yang Zhou Gene Therapy for NDDs, a Proof-of-Concept Test in Human Neurons $50,000
3 Alexandre Reynaud Dichoptic presentation of ebooks for the treatment of amblyopia and other visual conditions $49,676
1 Boris Bernhardt BrainScores: a tool for multimodal, quantitative, and collaborative MRI analysis $50,000
1 Reza Farivar The ICU Minder $50,000
4 Manuela Ferrari Game changer: Toward personalized diagnostics in youth mental health using Artificial Intelligence (AI) and video games $50,000
2 Leonard Levin Detection of Neurodegenerative Disorders Using Advanced Ocular Imaging $50,000

Ignite Grants Competition II

HBHL Research Theme Principal Investigator Project Title

Funding Received

4 Salah El Mestikawy Development of LMB1-01-002, a first in class product candidate to target anorexia $50,000
4 Tuong-Vi Nguyen Economic Impact Calculator for Perinatal Mental Health Disorders $50,000
1 Antonia Arnaert Prototype Development of the 鈥淪mart Back鈥 Wearable Health Device to Prevent and Manage Recurrent Low Back Pain among Adults $50,000
1 Patr铆cia Pelufo Silveira Building capacity for discovery and innovation in genomic datasets: the ePRS Cluster $50,000
3 Nancy Mayo GoHand to Enhance Recovery of Arm and Hand Function Post-Stroke $50,000
2 Simon Wing A Novel Assay for Identification of Inhibitors of a Deubiquitinating Enzyme for the Treatment of Parkinson's Disease $50,000
3 Derek Bowie Stable expression cell line of a therapeutically relevant AMPA receptor $50,000
2 Timothy Kennedy Polyglycerol dendrimer-based substrate for enhanced long-term cell culture $50,000
2 Philippe Gros Structure of USP15/inhibitor complexes to guide the discovery of new anti-inflammatory drugs $50,000
2 Thomas Durcan O2O - Organoid to Operator: The pathway to rapid and industry-standard dissemination of brain organoids to external users $50,000
1 Sylvain Williams Development of machine learning neuronal decoders predicting preclinical drug efficacy for Alzheimer's disease $50,000
1 Amir Shmuel Developing and evaluating methods for screening subjects and training subjects to stay still in mock scanners and MRI scanners $50,000

Ignite Grants Competition I

HBHL Research Theme Principal Investigator Project Title

Funding Received

4 Diane Boivin Personalized worker fatigue risk estimator $49,930
3 Derek Bowie Therapeutic treatment for Fragile X syndrome $50,000
2 Etienne de Villers-Sidani Design and Implementation of Novel Functional Eye-tracking Biomarkers for Neurodegenerative diseases

$50,000

2 Gabriella Gobbi Cannabidiol (CBD) for neuropathic pain and insomnia

$50,000

1 Ridha Joober Using novel AI-based techniques to model development of side effects in response to treatment in children with ADHD

$50,000

3 Nancy Mayo User Interface Development for Therapeutic Wearable: Heel2Toe Sensor $50,000
2 Nicolas Moitessier Prolyl oligopeptidase inhibitors as potential Parkinson鈥檚 disease therapeutics

$50,000

2 Gerhard Multhaup AIP Trap Technology to Prevent Cognitive Decline

$50,000

2 Guy Rouleau Clinical Development of Guanabenz as a Potential Disease-Modifying Therapy for the Rare Disease Spastic Paraplegia 4 $50,000
2 Reza Sharif-Naeini MP3- A Personalized Pain Management Platform $49,184

Funded Project Summaries

Ignite Grants Competition IV

Development and Testing of a Functional Prototype of an Interactive Augmented-Reality Based Surgical Guidance System for Spine Surgery

Pedicle screw placement is a technically demanding task, and in current practice, surgeons have to divide their attention between the operating field and the pre-operative patient images projected on a wall-mounted monitor; which may enhance errors. To support the surgeons鈥 performance, this project will 1) develop and test the effectiveness of a surgical guidance system (SGS) prototype using augmented reality, and 2) explore surgeons鈥 experiences using SGS鈥檚 functionalities. Qualitative and quantitative data, such as accuracy of screw placement, surgical time, and revision surgery rates, will be collected from 8 surgeons performing the pedicle screw placement on both artificial spine models and synthetic human cadavers. Central to the SGS development is the analytical framework used to guide and predict the surgeon鈥檚 behaviors, and as such prevent misplacement of the pedicle screw. The SGS is a novel software application that can be adapted to other surgical procedures beyond spine surgery.

HBHL Research Theme: 1

Principal Investigator: Antonia Arnaert

Funding Received: $50,000

Brain Health Probe

This grant is about developing a paradigm to test brain health in a way analogous to the knee-jerk reflex test. But the brain is, obviously, far more complicated. The brain consists of multiple large networks, and the coordinated activity across these networks is thought to underlie all our cognitive, perceptual and memory processes. Brain injury is thought to disrupt these networks, and we have had considerable evidence that this is likely true. A test of brain health that would be analogous to the knee-jerk reflex test would require a way of stimulating the brain objectively and then measuring brain responses. A popular, non-invasive method of brain stimulation is Transcranial Magnetic Stimulation, and an effective way of capturing brain activity is to use functional MRI, but these two technologies have not been very compatible. For example, until our recent invention, there has been no way of stimulating arbitrary positions on the head and imaging the entire head鈥攖hat is what our invention achieves.

HBHL Research Theme: 3

Principal Investigator: Reza Farivar

Co-applicant: William Matheiu

Funding Received: $50,000

Development of a gene therapy for ARSACS and intermediate filament disorders

Spastic ataxia of Charlevoix Saguenay (ARSACS) is an early onset autosomal recessive disorder caused by mutations in the gene encoding sacsin (SACS). Sacsin is a gigantic protein (520kDa) whose function is not yet understood, but evidence points to loss of function in ARSACS. Autosomal recessive disorders caused by loss of function of a gene are excellent candidates for the development of gene replacement therapy. However, gene replacement therapy is limited by the packaging capacities of current vectors used for gene therapy, which can contain a cDNA sequence to encode a 110kDa protein at best. We designed a compound that can replace sacsin and are assessing its therapeutic potential, efficacy in preventing and or delaying abnormal motor behavior and safety in mice models of ARSACS.

HBHL Research Theme: 2

Principal Investigator: Benoit Gentil

Funding Received: $50,000

Development of a companion research portal for data collection during AVATAR therapy for Auditory Hallucinations using an AVATAR therapy app

Many people with schizophrenia experience persecutory voices which may not respond to usual treatments like medications. AVATAR Therapy uses virtual reality to create digital representations of these voices (Avatars). With the help of a therapist, voice hearers can change the relationship with their voices, and feel better. AVAtalk Technologies has made an app that can make AVATAR therapy accessible to any therapist and patient with a smart phone. Our project involves developing a research portal which can be integrated into the app and provide information on many important questions. Do people improve clinically with this app as much as with the traditional virtual reality set-up? Are there aspects of culture, gender and ethnicity which should inform how treatment is administered? Do people treated with this app need less medication, or use health services less often? This portal will furnish data necessary to improve brain health outcomes in individuals with psychosis.

HBHL Research Theme: 4

Principal Investigator: Gail Myhr

Funding Received: $50,000

Ignite Grants Competition III

Extending Internet Multimodal Access to Graphical Exploration (IMAGE)

This project aims to increase access to visual media on the internet through a combination of audio and haptic (touch) interactions, augmenting the experience of blind users when they browse the web. Utilizing machine learning and other data processing techniques, we are building an information framework supporting engagement with graphics using a combination of sound and haptics (sense of touch). Our framework describes objects, relations between them, values on diagrams and charts, and relative road orientations and intersections for maps, turning these features into audio and haptic outputs designed to evoke the feeling of 鈥渟eeing a graphic鈥, but experiencing it through other sensory modalities. Using our system, blind users would gain a rich understanding of web graphics, a critical element of many web pages that are otherwise largely inaccessible to them.

HBHL Research Theme: 4

Principal Investigator: Jeremy Cooperstock

Funding Received: $50,000

Non-invasive control of pathological brain activity

Carefully choreographed patterns of neural activity are essential for many aspects of human behavior. When these rhythms are disrupted, which occurs in many forms of neurological disease, neurons lose their ability to process and transmit information. Instead, neurons begin firing in lockstep, producing wild oscillations in brain state that cause debilitating motor and cognitive symptoms. Restoring normal patterns of brain activity may relieve these symptoms and rescue patients鈥 quality of life. Here, we will continue the development of transcranial electrical stimulation, a non-invasive method for regulating the timing of neural activity. By testing it under conditions that closely match those occurring in neurological diseases, we will identify situations where it has the largest clinical benefit and speed its translation into a viable therapeutic.

HBHL Research Theme: 2

Principal Investigator: Christopher Pack

Funding Received: $49,883

A Novel Personalized Treatment Platform

Our platform addresses several challenges of personalized health management, including identifying effective treatments for patients, identifying novel patient subtypes, improving medical prediction models, enhancing drug development, and enabling collaborative healthcare. It enables inference of drug response for individual patients by modelling the patient phenotypic, genetic, and drug information as nodes, and the relationships between the nodes (i.e., drug genetic, patient-genetic, and patient-drug), in a graph. By using a combination of pharmacogenomic data, natural language processing (NLP) analysis of clinical notes, and graph convolutional neural networks, we capture patterns in the graph structure to predict whether any drug will be effective or result in side-effects, for any patient. Both patients and their MDs can contribute to expanding the graph, through creating a patient profile to provide knowledge of drugs that they have found to be effective for them (i.e., through their own N-of-1 treatment trial experience) and enable better predictions over time.

HBHL Research Theme: 2

Principal Investigator: Yannis Trakadis

Funding Received: $48,300

The Adaptive Reconfiguration Index: A Novel Tool for Prognosticating Recovery in Unresponsive Patients

Our team has recently developed a translational index that aims to accurately prognosticate recovery of consciousness in unresponsive patients in everyday clinical environments: The Adaptive Reconfiguration Index (ARI). The ARI measures the brain鈥檚 response to a neurophysiological perturbation by propofol anesthesia, using electroencephalography (EEG). Within the framework of Innovation Canada鈥檚 Technology Readiness levels, the ARI is currently a Level 5 technology: we have integrated the basic technology components, and validated the effectiveness of the system in the pilot study described above. Our objective in this Ignite grant is to advance the prototype to a Level 7 technology, where we will have a functional prototype ready for demonstration in the intensive care unit environment. This project aligns with HBHL's goal to support early-stage commercialization of a novel technology that will predict individual outcomes from severe neurological injury.

HBHL Research Theme: 1

Principal Investigator: Stefanie Blain-Moraes

Funding Received: $50,000

Gene Therapy for NDDs, a Proof-of-Concept Test in Human Neurons

Neurodevelopmental disorders (NDDs) are highly prevalent, heterogeneous brain disorders, exhibiting a wide range of neural and behavioral impairments yet unfortunately incurable till now. With growing numbers of identified genetic risk factors, it has become evident that pathogenic mutation of high-confidence risk genes implicated in the function of ionic channels, synaptic transmission plays causal roles in neurodevelopmental disorders. There is an urgent need to develop effective treatments for severe forms of NDDs, or manage its core symptoms, such as life-threatening seizures. We recently developed and optimized a genetic strategy that allows for repairing certain types of gene mutations. Our preliminary data indicate this genetic strategy show promising outcome in a mouse model of NDDs. In this Ignite grant, we aim to understand how our engineered genetic strategies can be harnessed to mitigate human neurodevelopmental disorders using iPSC-derived human neurons as a model system.

HBHL Research Theme: 3

Principal Investigator: Yang Zhou

Funding Received: $50,000

Dichoptic presentation of ebooks for the treatment of amblyopia and other visual conditions

Our invention delivers a binocular vision-based therapy that involves reading text made up of both binocularly and monocularly-presented letters. The point of this invention is to force the reader to use their two eyes together to train and improve binocular vision while reading. We foresee 3 main applications for it: the treatment of. amblyopia, the treatment of dissociated visual disorders and post-surgical eye re-alignment. We will develop a protype application for tablets, which patients can use to implement the therapy at home. This training will harness neuronal plasticity to improve vision function (sensory improvement) as well as eye alignment (motor improvement). Our reading methodology targets a very broad audience and offers an ideal platform that can be integrated into both work and leisure reading schemes. No need to have to spend 20 minutes a day doing tedious eye exercises if they can be part and parcel of one鈥檚 everyday activities.

HBHL Research Theme: 3

Principal Investigator: Alexandre Reynaud

Funding Received: $49,676

BrainScores: a tool for multimodal, quantitative, and collaborative MRI analysis

Neuroimaging, and in particular magnetic resonance imaging (MRI), offers a 3D window into the structure and function of the brain. In addition to having advanced our understanding of brain organization, neuroimaging promises to improve diagnosis, prognosis, and treatment of numerous brain disorders. Disorders where neuroimaging has immense potential to revolutionize clinical decision-making and increase patient wellbeing while reducing healthcare costs. The technology BrainScores aims to develop a better neuroimaging tool that would enable quicker, integrated, automated, and collaborative MRI analysis. A multimodal and collaborative approach will help correct diagnostic/prognostic errors and therefore deliver more accurate and better care for patients. We aim to provide a novel and accessible tool to visualize and analyze neuroimages that combines i) Multimodal data fusion, leveraging multimodal image processing to place different MRI contrasts into a common space so that they can be simultaneously inspected and analyzed, and compared to images from other subjects; ii) BrainScores computation, based on compact representations with 鈥渉otspots鈥 that index atypicality and highlight salient information for human observers and AI-based decision support systems; and iii) MRI annotation and collaboration, by incorporating an interactive app with capacities for MRI viewing, inspection of brainscores, annotation, and collaboration among experts, knowledge users, and AI.

HBHL Research Theme: 1

Principal Investigator: Boris Bernhardt

Funding Received: $50,000

The ICU Minder

Patients in the ICU are carefully monitored, but the way this monitoring is done leaves opportunity for massive improvement. For example, to determine changes to the patient occurring over hours, days, and weeks, clinicians jot down patient vitals and treatments every 15 minutes on paper charts, with one chart being for one day, meaning that reading across days can be difficult. The tabular form can be very difficult for discerning trends. Finally--and crucially--the clinicians seldom know the period of wakefulness or whether the patient experiences discomfort, unless they happen to be in the room when the patient expresses these. The ICU Minder is a tool that combines video capture, AI analysis, along with timeseries logging and visualization, to overcome all of these challenges.

HBHL Research Theme: 1

Principal Investigator: Reza Farivar

Funding Received: $50,000

Game changer: Toward personalized diagnostics in youth mental health using Artificial Intelligence (AI) and video games

Could AI and video games be the solution for detecting and managing the onset of mental health problems in youth? Bringing together measurementbased care and artificial intelligence (AI), 鈥淕ame changer鈥 is a video-game assessment tool that can detect and monitor the evolution of mood and emotional changes and predict help-seeking behaviors among youth struggling with early-onset mental health problems, particularly psychosis. A proven therapeutic tool, gaming provides a familiar and entertaining environment for supporting access to evidence-based treatment. Building on recent advances in digital health research, this digital tool may potentially revolutionize mental health assessment in psychiatry by generating a large quantity of data supporting the capacity to implement precision medicine and a stepwise approach to care.

HBHL Research Theme: 4

Principal Investigator: Manuela Ferrari

Funding Received: $50,000

Detection of Neurodegenerative Disorders Using Advanced Ocular Imaging

The goal of this study is to determine whether the earliest signs of several neurodegenerations can be identified in the front of the eye, using state-of-the-art techniques for visualizing parts of the eye at high magnification. We already know that parts of the eye can be abnormal in some of these diseases, e.g. neurofibromatosis, but we believe that using advanced techniques, we can do this automatically and more sensitively than what is done now. This will contribute to one of HBHL鈥檚 goals, of 鈥淓arly diagnosis, detection of disease progression and response to therapy.鈥 The same technology will also be developed for allowing remote examination of the front of the eye, and should have a broad impact in communities where ophthalmic care is not readily available, e.g. Indigenous communities.

HBHL Research Theme: 2

Principal Investigator: Leonard Levin

Funding Received: $50,000

Ignite Grants Competition II

Development of LMB1-01-002, a first in class product candidate to target anorexia

Almost 1 million Canadians suffer from eating disorders such as anorexia nervosa. Currently, there is no specific treatment for anorexia nervosa. Excessive habits are at the heart of self-destructive behaviors observed in anorexia. We recently established that the neurotransmitter named acetylcholine is a pivotal regulator of anorexia-like behavior in mice. We also identified that donepezil (Aricept), a well-known acetylcholine esterase inhibitor, corrects these deficits. These findings represent a major breakthrough in the field. However, pro-cholinergic drugs (such as donepezil) have numerous peripheral side effects. We propose to develop derivates of donepezil with increased capacity to penetrate the brain. We will use a virtual screening strategy to design donepezil analogs and will test them in our mouse models. Lower doses of these compounds will be necessary to treat patients and deleterious side effects will be reduced. Our project will open the way to the first specific pharmacological treatment of anorexia.

HBHL Research Theme: 4

Principal Investigator: Salah El Mestikawy

Funding Received: $50,000

Economic Impact Calculator for Perinatal Mental Health Disorders

Up to 20% (if not more) women develop a perinatal mental health disorder during pregnancy or within 1 year postpartum. Yet there is no national perinatal mental health strategy, no official perinatal mental health screening guidelines and no validated tool to measure the long-term costs of perinatal mental health disorders to society. We created an economic impact calculator to calculate cost-benefit ratio and provide a quantifiable measure of the gap between current public health spending in perinatal mental health and optimal level of spending to minimize long-term costs to society due to maternal disability and child neurodevelopment disorders.

HBHL Research Theme: 4

Principal Investigator: Tuong-Vi Nguyen

Funding Received: $50,000

Prototype Development of the 鈥淪mart Back鈥 Wearable Health Device to Prevent and Manage Recurrent Low Back Pain among Adults

The prevalence of non-specific low back pain (LBP), caused by segmental instability of the lumbar spine, is reported to be 84%. Recurrences within 1 year following recovering after the acute episode are common, and the costs associated with chronic LBP represent a significant economic burden to healthcare systems. This project will develop the prototype of the 鈥淪mart Back鈥 wearable health device, based on the neutral zone (NZ) concept, that aims to strengthen the deep lumbar multifidus muscle (D-LMM) to prevent and manage recurrent LBP among adults. The D-LMM is the main back stabilizer: strengthening this muscle in isolation will bring the NZ to its normal position, hence reducing LPB. Sensor fusion and artificial intelligence will be used to define the intensities of the electrical stimulation. The novelty of this device lies in the ability of imaging sensors to monitor the thickness of the D-LMM, a parameter to define muscle atrophy. Smart Back is a non-invasive, spine corrective wearable device that can stimulate the deep layers of lumbar muscle to improve posture and relieve chronic neck and lower back pain. The value proposition is to address the lumbar muscle dysfunction root cause while relieving pain and improving posture. This approach allows to stop muscle atrophy, relieve pain with no to minimal side effects.

HBHL Research Theme: 1

Principal Investigator: Antonia Arnaert

Funding Received: $50,000

Building capacity for discovery and innovation in genomic datasets: the ePRS Cluster

The decreasing costs of technologies involving the use of genomic information have expanded the use of this technology by many scientists in different studies. However, the use of this technology imposes challenges and requires highly specialized personnel. We propose to create a specialized cluster that could accommodate this service and provide a faster solution to different needs, by means of immediate access to processing pipelines, designing and deriving polygenic scores, and/or interpreting and communicating results. Such facility could accelerate the process of scientific discovery and optimize the use of valuable data from small scale studies. Ultimately, this service will contribute for improving individuals鈥 health and Canadian human capital.

HBHL Research Theme: 1

Principal Investigator: Patr铆cia Pelufo Silveira

Funding Received: $50,000

GoHand to Enhance Recovery of Arm and Hand Function Post-Stroke

One of the most frustrating and persistent motor sequelae of stroke is poor arm and hand function. Many therapies have been tried for arm function post-stroke but the most effective require extensive practice and repetition of movements and tasks. Even with this extensive practice, effects are moderate with little or no carry over into arm and hand use every day, real-world, activities. We have developed a sensing and feedback device, GoHandTM, that provides auditory feedback for finger and hand movements. This type of positive auditory feedback is known to stimulate neural connections and, through the process of neural plasticity, imprint the learned movement pattern. The sensor also provides performance feedback that is motivating allowing patients to set and accomplish movement and practice goals and track progress. The sensor also has the capacity to measure movements of the arm and hand independently, metrics needed for the rigorous evaluation of recovery.

HBHL Research Theme: 3

Principal Investigator: Nancy Mayo

Funding Received: $50,000

A Novel Assay for Identification of Inhibitors of a Deubiquitinating Enzyme for the Treatment of Parkinson's Disease

Parkinson鈥檚 disease (PD) is a growing devastating neurodegenerative disorder. Yet, since the discovery of L-DOPA in ~1960, there have been no new advances in the disease modifying therapies. The classical hallmark of PD is a progressive loss of brain cells and an accumulation of protein clumps termed Lewy bodies (LBs). LBs appear early in PD and spread throughout the brain ultimately leading to a loss of brain cells. Our research has revealed that PD mice lacking an enzyme called USP19 spread less protein clumps than normal mice. Therefore, our goal now is to identify a drug that can inhibit USP19 and thereby have a similar effect. We will test a new approach to identifying drugs for USP19 and similar enzymes, which are notoriously difficult to drug. Our research may therefore not only identify a new drug for PD, but also provide a platform for drug discovery in other neurodegenerative diseases.

HBHL Research Theme: 2

Principal Investigator: Simon Wing

Funding Received: $50,000

Stable expression cell line of a therapeutically relevant AMPA receptor

AMPA-type ionotropic glutamate receptors (AMPARs) are the most abundant neurotransmitter receptor in the mammalian brain. AMPARs are fundamental for mediating fast glutamatergic transmission in the brain but have also been implicated in numerous CNS disorders. A specific class of AMPARs, which are highly permeable to Ca2+ and Zn2+, are proposed to trigger cell death in numerous intractable neurological disorders that include stroke, glioblastoma multiforme, glaucoma and other neurodegenerative disorders. A challenge in targeting this class of AMPARs is that their biochemical make-up is unknown. The proposed project will build upon unpublished findings from my lab identifying the composition of the AMPAR responsible for cell death in CNS disease. Funds are therefore requested to generate two cell lines that can be used as a valuable screening tool for the small to large pharmaceutical industry to identify selective molecules with therapeutic value.

HBHL Research Theme: 3

Principal Investigator: Derek Bowie

Funding Received: $50,000

Polyglycerol dendrimer-based substrate for enhanced long-term cell culture

Living cells can be maintained in the laboratory using a technique called cell culture. This allows cellular and molecular mechanisms of disease to be identified and studied, and possible drugs and treatments to be tested. Neurons are particularly delicate cells and neurons made from patient derived stem cells (hiPSCs) require long-term support to develop the mature characteristics that are critical to study neurodegenerative disease. A major limitation of long term cell culture is that the cells actively degrade the molecular matrix that is initially added to support their growth. This ultimately destabilizes the cultures and results in cell death. We have developed a new surface coating that is highly stable and resists cell induced degradation. This coating is inexpensive to produce, straightforward to use and easily adapted to existing cell culture protocols. We believe that this is a 鈥済ame changing鈥 technology to support long term neural cell culture.

HBHL Research Theme: 2

Principal Investigator: Timothy Kennedy

Funding Received: $50,000

Structure of USP15/inhibitor complexes to guide the discovery of new anti-inflammatory drugs

Neuroinflammation is a key component of neurological diseases such as multiple sclerosis, Azheimer's and Parkinson. The USP15 de-ubiquitinase plays a central role in neuroinflammation by promoting the production of pro-inflammatory molecules by brain cells (microglia, astrocytes) in response inflammatory or tissue injury insults. We are developing novel small molecule inhibitors to block USP15 action in vivo, and have identified potent candidates. We wish to determine the high resolution crystal structure of USP15/inhibitor complexes to guide structure/activity relationship studies for more efficacious drugs. The development of novel anti-inflammatory drugs will improve the health of Canadian afflicted by these common diseases, a key goal of theme 2 of the HBHL program. The participation of Corbin Thera (licensed industry partner) will increase local economic impact through hiring of HPQ, and will enhance development of 平特五不中-based IP.

HBHL Research Theme: 2

Principal Investigator: Philippe Gros

Funding Received: $50,000

O2O - Organoid to Operator: The pathway to rapid and industry-standard dissemination of brain organoids to external users

With the advent of stem cells, we can now generate human neuronal tissue from the different regions in the brain, commonly referred to as brain organoids. With all the features of human tissue, we now have a human model to find new therapies. Yet, the specialized nature and cost means few labs and companies work with brain organoids, and instead rely on conventional models that have proven to be problematic in finding new therapies. It is this gap we seek to fill. With methods established to grow brain organoids by the thousands, reducing both costs while increasing standardization, these brain organoids are now at a readiness to be used by researchers anywhere in the world. Thus, we aim to refine our shipping process, so that we will be poised to ship living brain organoids, to anyone, anywhere in the world, opening up this model to the masses.

HBHL Research Theme: 2

Principal Investigator: Thomas Durcan

Funding Received: $50,000

Development of machine learning neuronal decoders predicting preclinical drug efficacy for Alzheimer's disease

Using large scale population imaging data in mice performing memory task, the objective is to develop machine learning algorithms that will use large scale population data to perform predictions on the efficacy of lead compounds in preclinical AD mice models. This will be done by establishing signatures of normal and defective neural coding and determining whether lead compounds can effectively rescue normal coding in AD mice models. The goal is to be able to quantify and predict the effectiveness of a compound in rescuing memory and help translation of a treatment from preclinical to human AD. ii) This project is well aligned with theme 1 whose end point is to help develop new analytical methods using multiple dimensions (imaging and behavior). iii) Finding the algorithms predicting drug efficacy in AD will enhance the probability of translating drugs from the preclinical to AD patients, a disease where there are no functioning drugs at this moment that can stop the progression of the disease and reverse the important symptoms of memory loss.

HBHL Research Theme: 1

Principal Investigator: Sylvain Williams

Funding Received: $50,000

Developing and evaluating methods for screening subjects and training subjects to stay still in mock scanners and MRI scanners

Head and body movements introduce artifacts in structural, diffusion, and functional MRI. With the advent of imaging at ultra-high field, head and body movements limit our capacity to obtain high-resolution, high-quality data. We have developed a small wearable device for acquiring data on head and body movements and transmitting it wirelessly to a computer for real-time analysis while a subject is trained in a mock MRI scanner. We will further develop the system to give feedback and reward to subjects for staying still in a mock scanner or an MRI scanner. The system will allow for screening and training subjects, including children and subjects with neurodevelopmental disorders, for obtaining high-quality MRI data that can be used for modeling brain structure and function in health and disease.

HBHL Research Theme: 1

Principal Investigator: Amir Shmuel

Funding Received: $50,000

Ignite Grants Competition I

Personalized worker fatigue risk estimator

Sleep deprivation and circadian disturbances significantly reduces the mental and physical health of shift workers in addition to decreasing their productivity and increasing their risk of incidents and accidents. Fatigue-related risks greatly varies between individual workers. The objectives of the present project is to establish the factors that affect an individual鈥檚 susceptibility to become impaired by fatigue while working on atypical schedules. It will pursue the question as to whether susceptibility to work on atypical schedules vary greatly between individuals but is quite stable in the same persons. To achieve our objectives, we will analyse a large database of fatigue measures collected in over 70 individuals throughout an entire month-long work roster each. This project will help us understand the factors that shape individual and population differences in terms of their susceptibility working on atypical schedules. It will contribute to promoting brain health and functional capacity across diverse working populations.

HBHL Research Theme: 4

Principal Investigator: Diane Boivin

Funding Received: $49,930

Therapeutic treatment for Fragile X syndrome

Fragile X syndrome (FXS) is a genetic disorder affecting 1 in 4,000-6,000 individuals worldwide. The disease is characterized by learning disabilities, cognitive impairment and autism. There is currently no cure for FXS, however, the gene responsible for the condition has been identified as being FMR1 (fragile X mental retardation 1) which encodes the protein, Fragile X Mental Retardation Protein (FMRP). FMRP is present at almost all excitatory nerve junctions in the human brain where it plays prominent roles in neuronal signaling and learning mechanisms. Individuals with FXS fail to express FMRP and thus lose these critical functions. In this grant application, we identify a small molecule that rescues excitatory signaling in a mouse model of FXS. Funds are requested to test the effectiveness of a family of related molecules in restoring behaviorial deficits in a preclinical model of FXS which will provide the rationale for testing in patients.

HBHL Research Theme: 3

Principal Investigator: Derek Bowie

Funding Received: $50,000

Design and Implementation of Novel Functional Eye-tracking Biomarkers for Neurodegenerative diseases

We propose to develop a new software-based technology to aid with the early diagnosis of certain neurodegenerative disorders. This diagnosis aid aims takes advantage of the fact that during the pre-symptomatic phase of many such disorders, subtle abnormalities in eye movements are often present and can be a source of valuable information for differential diagnosis. Funds obtained through this grant would be used to carry out a pilot study in select neurological patient populations where we would measure various eye movement parameters鈥攗sing our recently designed suite of visual tasks and a new eye-tracking technology that only requires the front camera of mobile phones and tablets鈥攁nd use machine learning classifying algorithms to parse patient populations and disease states. Our long-term vision is to develop disease-specific functional eye-movement biomarkers to assist with the assessment of disease status and progression, and to serve as a platform to test the effects of therapeutic agents.

HBHL Research Theme: 2

Principal Investigator: Etienne de Villers-Sidani

Funding Received: $50,000

Cannabidiol (CBD) for neuropathic pain and insomnia

1) The goal of the project is to test if the cannabidiol (CBD) can treat chronic neuropathic pain and insomnia. 2) The project is aligned with the HBHL objectives since it aims to discover novel treatments for brain disorders. 3) In the past 3 years 14,000 Canadians have died from opioid overdose and 17,000 were hospitalized for opioid side effects, and most were people with chronic pain. Research on novel treatment for chronic pain is a priority for Canada.

HBHL Research Theme: 2

Principal Investigator: Gabriella Gobbi

Funding Received: $50,000

Using novel AI-based techniques to model development of side effects in response to treatment in children with ADHD

ADHD is the most common psychiatric disorder in children. There is significant variability in the way a child responds to treatment, particularly in development of side effects- several factors appear to be involved. We propose to use an interdisciplinary approach to develop a novel Artificial Intelligence-based technology to model the development of side effects. An agent-based modeling technique will be combined with a machine learning- based approach to build this model. The model will be validated using data that has been collected (n=860 children with ADHD). While conducting a double-blind, placebo-controlled trial with a low dose of Ritalin, data on social, clinical, and biological factors (genetics, environmental events, epigenetics and brain structure information) has been collected. If successfully validated, this method may become an important tool that may be used by clinicians, with the potential of being extended to predict overall treatment response in ADHD and other complex psychiatric disorders.

HBHL Research Theme: 1

Principal Investigator: Ridha Joober

Funding Received: $50,000

User Interface Development for Therapeutic Wearable: Heel2Toe Sensor

Many people do no walk well placing themselves at risk of falls, further injury, and health deterioration. Instructing people to place the heel first when walking is how therapists encourage correct gait. This simple strategy changes posture from stooped to upright and lengthens the stride. But once verbal cueing ceases, the inefficient foot-flat gait returns. Our team has developed a sensing and a biofeedback device that provides auditory feedback for each 鈥済ood鈥 step based on the step having sufficient heel strike. The Heel2Toe device clips to the outside of the shoe. This project will help commercialize Heel2Toe and make it available to people who want to walk better and to therapists. We need to create a way of communicating to users and therapists what areas of walking need to be improved. Funding will provide resources for a mobile app and testing to make sure it is useful and user-friendly.

HBHL Research Theme: 3

Principal Investigator: Nancy Mayo

Funding Received: $50,000

Prolyl oligopeptidase inhibitors as potential Parkinson鈥檚 disease therapeutics

Parkinson鈥檚 disease (PD) is a pathology that will affect 1 in 500 Canadians in their lives. PD is diagnosed by the death of neurons in the brain and by the appearance of protein aggregates made of 伪-synuclein (伪-syn). We have developed molecules that are able to inhibit a protein, prolyl oligopeptidase (POP), that is known to induce aggregation of 伪-synuclein. While we know that our lead compounds can inhibit POP, we now propose to further test them for their ability to prevent 伪-synuclein aggregation in neurons and advance them closer to in vivo testing. In the long term, the successful identification of molecules inhibiting 伪-synuclein aggregation will moved to more advanced animal models. There is currently no POP inhibitor in clinical trials nor efficient PD treatments. Ultimately, we hope that our work will improve the life of Canadians affected by PD.

HBHL Research Theme: 2

Principal Investigator: Nicolas Moitessier

Funding Received: $50,000

AIP Trap Technology to Prevent Cognitive Decline

Alzheimer disease (AD) is the most prevalent neurodegenerative disorder in the world, estimated to currently affect over 35 million people globally. As the number of Canadian elderly suffering from neurodegeneration and cognitive decline is rapidly increasing, earlier intervention strategies are urgently needed in the clinics. In part, AD neurodegeneration is caused by a specific peptide (amyloid-beta (Abeta)) that forms toxic aggregates in the brain. Recently, we have identified an Abeta-oligomer Interacting Peptide (AIP) that provides beneficial effects by decreasing Abeta neurotoxicity. This proposal will test a novel, next generation molecule, i.e. our unique D-AIP peptide, determine its pharmacological potential in transgenic mouse models of Alzheimer disease and investigate the mechanisms how it inhibits neurotoxicity of Abeta in animals. We have already shown that D-AIP is metabolically stable, rescues amyloid toxicity in cells and tissue culture and can penetrate the blood brain barrier of wildtype mice.

HBHL Research Theme: 2

Principal Investigator: Gerhard Multhaup

Funding Received: $50,000

Clinical Development of Guanabenz as a Potential Disease-Modifying Therapy for the Rare Disease Spastic Paraplegia 4

Spastic paraplegia 4 (SPG4) is the most common form of a rare neurodegenerative disorder called hereditary spastic paraplegia (HSP), which is characterized by muscle stiffness and weakness in the legs that worsens over time. There are no therapies for HSP, and treatment is limited to improving symptoms. Based on preclinical evidence, we plan to conduct a clinical trial to determine if guanabenz, a drug used to treat high blood pressure, is a safe and effective therapy for patients with SPG4. Our goal is to obtain Health Canada approval for guanabenz as a treatment for SPG4. This project is aligned with HBHL objectives by proposing innovative research approaches to improve a rare genetic neurodegenerative disease through treatment, and to advance a drug toward early-stage commercialization. This project has the potential to positively impact the clinical research and pharmaceutical markets in Canada, as well as benefit clinicians, researchers, and patients with HSP.

HBHL Research Theme: 2

Principal Investigator: Guy Rouleau

Funding Received: $50,000

MP3- A Personalized Pain Management Platform

Chronic pain afflicts 30% of Canadians and has an economic impact of more than $40billion per year in direct and indirect costs. Typical pain management therapies take 2-3 years to find an effective analgesic for a patient. But this long delay brings secondary morbidities, including anxiety, depression, and suicide ideation. We developed a platform that accelerates the screening of analgesic drugs to find one tailored to the patient鈥檚 genetic make-up. We propose to validate this technology with the collaboration of a clinical and a patient with chronic pain. Our objective is to bring this technology to market to expedite the pain management process of these patients.

HBHL Research Theme: 2

Principal Investigator: Reza Sharif-Naeini

Funding Received: $49,184

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