Health Research BC – Mitacs Industry-Based Opportunity

Safety Assessment of Antimicrobial Peptides

Background:

Antimicrobials are substances that eliminate or prevent the growth of disease-causing microbes. The predominant type of antimicrobial used to combat infections is antibiotics. The introduction of antibiotics in modern medicine significantly transformed the treatment of infectious diseases worldwide. However, since 1987, antibiotics research has experienced what is known as “the discovery void,” during which no groundbreaking agents have been discovered. Concurrently, existing antibiotics are becoming less effective against various life-threatening infections, which presents a serious global health threat. With the current trajectory, it is anticipated that deaths associated with infections will rise dramatically in the upcoming years. In recent years, small protein molecules called antimicrobial peptides (AMPs) have emerged as a promising avenue to address the innovation gap in antibiotic development.

Project Objectives

The central objective of this project is to examine the safety of recently discovered AMPs, which were discovered using computational methods. Our safety assessment experiments include:

Resistance Emergence Examination: Investigating whether AMPs have the potential to become less effective upon continued administration.
Hemolysis Assays: Evaluating whether AMPs cause damage to red blood cells.
Cytotoxicity Assays: Assessing the adverse effect of AMPs on various tissues.
In Vivo Assessment in Mice: Determining the effectiveness and potential adverse effect of AMPs in a live animal model.

Development of Skills and Competence:

Throughout the placement, the trainee will gain and expand upon a diverse range of valuable personal and professional skills in academia and industry. Among others, the intern is expected to develop skill and competence in:

Scientific and Technical Proficiency: The intern will acquire practical experience in designing scientific experiments, generating data, and analyzing biological data.
Problem-solving and Decision-Making: The trainee will be guided by world-class scientists throughout placement. As the project advances, the intern will foster critical thinking and decision-making skills to assess and troubleshoot experiments.
Planning and Prioritizing: The trainee will develop essential skills in overseeing various tasks while meeting internal and external deadlines.
Communication: The intern will refine verbal and written communication skills crucial for reporting findings to both scientific and non-scientific audiences. Further, the intern will be able to develop networking skills while attending meetings with collaborators and industry partners.
Ethics: The internship allows the trainee to gain a deep understanding of ethical standards in animal experimentation, aligning with provincial and federal guidelines.
Teamwork and Collaboration: The intern is expected to develop the ability to work effectively within interdisciplinary teams while implementing academic insights with industry applications.
Leadership and Initiative: The intern will enhance their leadership skills by leading certain project components, introducing innovative research directions, and mentoring peers.
Career and Skill Development: The internship will enable the intern to broaden their career perspective within the life science sector while facilitating their transition from academic to industry roles.

How the Project and Internship Support Amphoraxe Inc.:

This project and internship enable Amphoraxe Inc. to accelerate the advancement of antimicrobial research while supporting key operational and strategic areas:

Innovation and Development: The biological experiments in this project align with Amphoraxe’s core mission of developing effective alternatives to traditional antibiotics. In particular, the result obtained from this project will expedite the development of AMPs from the laboratory to the market.
Resource Optimization: This internship facilitates a cost-effective approach to research and development by integrating academic resources and Amphoraxe’s industry capabilities.
Regulatory Support: The safety assessments conducted in this project will provide Amphoraxe with experimental data critical for product optimization and regulatory submissions.
Talent Development and Recruitment: The internship serves as a unique platform to train and nurture trainees, thus making them potential candidates for future employment.
Future Opportunities: The scientific outcomes from this internship program could lead to further funding and research opportunities, reinforcing Amphoraxe’s innovative research in the life sciences sector.

Privacy-Preserving Human Activity Recognition for Healthcare using Large Vision-Language Models

Background

The world is aging quickly. Most senior or elderly people prefer to aging at homes. Many of them live alone, but they face many challenges to their health and safety. On the other hand, in the value-based healthcare system, there are growing demands to monitor the activities of patients at homes, and even identify some diseases earlier to reduce the cost to the healthcare system. How to monitor the health and safety of seniors and patients while respecting their privacy is a great challenge.

Since 2018, AltumView has developed the Sentinare smart activity sensor for senior care and remote patient monitoring. It uses the latest AI technology to monitor the activity of people, collect health statistics, and notify caregivers when emergencies such as falls are detected. To protect privacy, only stick figure animations are transmitted instead of videos.

AltumView has become a global leader in privacy-preserving AI for healthcare. Its product received CES 2021 Innovation Award Honoree, and is one of only three fall detection devices integrated into Amazon’s Alexa Together emergency service.

The aims/ objectives of the project

Currently AltumView’s algorithms are operating in the sensor. Due to the limited computational resources in the sensor, these algorithms can only detect basic actions such as standing, sitting, and falling.

In this project, we aim to develop cloud-based algorithms to recognize more complicated activities, including activities of daily living (ADLs), such as eating, drinking, and cooking. Being able to recognize these activities will provide valuable information to the family and doctors to monitor the health and safety of the seniors and patients.

Based on the stick figure data from AltumView’s product, our long-term goal is to develop algorithms to perform cognitive assessment, and identify some behavioral diseases earlier, such as Parkinson’s disease, dementia, anxiety, depression, and autism, by collaborating with more physicians and hospitals.

The skills/ competencies the intern is expected to develop through the internship

The intern should have good knowledge of deep learning. In the project, the intern will learn more on privacy-preserving AI, especially the latest large-model-based AIs. The intern will also learn valuable product development experience, and how to combine research and product development under various constraints.

How the project and internship will support the company

In this project, the intern will learn and develop algorithms using various latest tools in AI, such as Graph Convolution Network (GCN), Graph Transformer (GT), and large-language-models (LLM) and large-vision-language-models (VLM) such as ChatGPT and Sora, which have demonstrated revolutionary performances in many fields. AltumView is also the only company in the world that has accumulated millions of hours of privacy-preserving stick figure data, which is extremely valuable in developing large-model-based AI algorithms.

The intern will focus on two aspects:

We will focus on developing stick-figure-based methods, since AltumView sensor only transmits stick figures to the server. Although there have been some stick figure-based GCN and GT methods, stick-figure-based VLM methods have not been well studied. This creates a good opportunity to make some breakthrough in this unique and important field, given the enormous practical application potential of AltumView’s product. It will significantly enhance AltumView’s competitiveness in the market.
We will focus on developing low-cost and high-performance algorithms. Since our algorithms only use stick figure instead of videos, its complexity is already much lower than video-based methods. If we can further reduce the complexity of stick-figure-based methods without sacrificing too much the performance, we will have a great advantage compared to other products.

In summary, this project will develop novel privacy-preserving AI algorithms for healthcare, apply them to AltumView’s product, enhance its leadership in the market, help more seniors and patients around the world, and contribute to Canada’s economy.

Development and validation of in vivo models of acute bacterial infections for use in novel drug development

Bacterial infections are one of the main causes of mortality and long-term patient complications worldwide. For example, pneumonia is the number one cause of death in children under 5. The primary driver of toxicity resulting in organ failure and death during these infections are components of the bacteria themselves, called endotoxins. These are components of the bacterial membrane that the body’s immune system senses and then triggers massive inflammation as a result, and this causes associated organ damage. When present in high abundance, this can cause severe inflammation resulting in death. The condition in which an infection results in high levels of endotoxin in the blood is referred to as endotoxemia and is the main driver of mortality in these infections. Endotoxemia conditions include pneumonia, and others for which few good therapeutics exist. Developing drugs to reduce the time to resolution of endotoxemia is the goal of this proposal.

Over decades it has been established that endotoxins are sequestered and cleared from circulation via high- and low-density lipoproteins (HDL and LDL respectively). These complexes bind endotoxin and are then cleared into the bile via the liver in a pathway overlapping that of cholesterol metabolism. From extensive clinical studies, it was recently discovered that patients with mutations in genes that result in increased function in the HDL and/or LDL pathways have superior outcomes from severe endotoxemia-related infections such as sepsis than the average population. For example, patients with mutations in the PCSK9 gene have a ~85% overall survival rate after 1 year, whereas this is ~60% in the average population. This and other proteins are largely made in the liver, which is a highly druggable organ using genetic drugs delivered via lipid nanoparticles (LNP).

Resolve Nanotherapeutics is a preclinical drug development company creating LNP RNA drugs that will either mimic or improve on these clinical observations by upregulating endotoxin clearance pathways after intravenous infusions. RNTx has significant expertise in RNA LNP drug development but critically lacks disease challenge models to test its drugs – a non-trivial task that will dictate the direction of clinical development of any new drug formulations. We have identified a strong bacterial infectious disease post-doctoral fellow interesting in developing and testing of drugs in at least 3 in vivo challenge models, and setting these up and doing efficacy testing is the basis of this proposal.

The aims are as follows:
1. Develop an in vivo model of bacterial pneumonia for at least 4 diverse bacterial pathogens
2. Develop and in vivo model of bacterial sepsis
3. Develop an in vivo model of chemotherapy induced (febrile) neutropenia

The fellow will develop hands on skills for in in vivo infection models and testing drug formulations therein. They will also gain experience in drug development, both by exposure to the drug development process in terms of design, but critically learn to assess in vivo requirements such as pharmacokinetics, biodistribution, toxicity, efficacy, and many other evaluations. These are invaluable skills highly translatable to other sectors of drug development.

The project will greatly accelerate the capacity of Resolve NTx to perform drug candidate efficacy testing and ultimately chart the fastest path to clinical to get these potentially critical drugs into patients as fast as possible.

LNP-mRNA as a treatment for neurological dysfunction of Gaucher Disease

Brain disorders affect 10% of Canadians, however few treatment options exist for these devastating diseases. We have extensive understanding of what causes many of them, but current medical technology has yet to translate this knowledge into effective treatments. For example, many natural proteins have been identified to hold significant therapeutic promise, but getting these proteins to the brain has been a longstanding challenge. Our group has developed a technology that empowers the brain to produce its own therapeutic proteins to treat brain disorders. Using a technology similar to the COVID vaccine that combines lipid nanoparticles (LNP) and messenger RNA (mRNA), we can transform brain cells into protein factories that continually produce these therapeutics proteins over days to weeks. We have proof of concept data in mice demonstrating this strategy is tunable and achieves long lasting brain-wide biodistribution of desired proteins, requiring fewer infusions compared to existing treatments.

The proposed collaboration with the MacVicar Lab at UBC is to develop an LNP-RNA based treatment for Gaucher Disease (GD, Types I-III). GD is a rare lysosomal storage disorder caused by mutations in the GBA gene coding for the vital enzyme Glucocerebrosidase (GCase). GCase deficiency in GD manifests as a spectrum of brain disease, from rapid neurodegeneration and death in infancy or early childhood (Type II), to saccade eye movements to epilepsies, to dementia (Type III). Even Type I, which is often considered ‘non-neuronopathic’, has been shown to be strongly correlated with Parkinson’s disease and related neurological symptoms. GD Types I and III are treated with biweekly intravenous infusion of Imiglucerase (Cerezyme®), an enzyme supplement for GCase. However, Imiglucerase has no impact on neurological symptoms in GD because it does not reach brain tissues.

We propose to use our Bioreactor strategy to manufacture GCase directly in the brain as a treatment of neurological GD. Our group uses brain-optimized LNPs to achieve widespread LNP-mRNA uptake in disease-agnostic cells in the central nervous system to transform them into Bioreactor cells. These Bioreactor cells will translate the mRNA into functional GCase, which is released to the entire brain to effectively replace the dysfunctional GCase that causes GD. As a first step, we must engineer GCase mRNAs for optimal GCase production and longevity in Bioreactor cells. The intern, Dr. Daniel Andrews, a trained mRNA biochemist, will conduct key studies in cell culture models to generate optimized mRNA constructs for GCase. This work will be split in four Aims; (1) to establish a reliable cell culture system to produce and test mRNAs for GCase, (2) to engineer mRNA sequences for GCase to optimal expression in these cell cultures, and (3) to compare the enzymatic function of GCase from different mRNA constructs produced in cell cultures to identify lead candidates for animal testing, and (4) encapsulate mRNAs into LNPs for brain injections in mice.

Dr. MacVicar has over 37 years of experience as a neuroscientist with a proven track record of training young scientists that go on to faculty positions in academia, medicine, industry, and government agencies. Dr. Andrews will work closely with neuroscientists in the MacVicar laboratory, where he will develop expertise in the field, as well as technical training on state-of-the-art laser imaging microscopes. Dr. Andrews will also be directly involved in training and mentoring students in the lab to further develop his leadership skills. Dr. MacVicar’s ongoing collaborations with Dr. Pieter Cullis, a world leader in LNP-based nanomedicines, will position Dr. Andrews at the forefront of next-generation therapeutic development, with access to UBC’s vast network of RNA and nanomedicines experts and ability to produce high quality research. Dr. Andrews will also be exposed to a breadth of training opportunities at CCNTx that would only be possible at a small startup company. Dr. Andrews will be directly involved in higher-level R&D and IP planning related to CCNTx operations. This will include participating in IP strategy, forward-looking research objectives, business development activities, and attending industry conferences. This will place Dr. Andrews in a position to contribute both to the R&D and the growth of the company during its formative stages.

CCNTx is a UBC spinoff company and technology transfer partner. The data generated by the project is likely to generate new intellectual property (IP) that will be further developed by CCNTx for future commercialization. As a startup company, building an IP portfolio will be critical for future success and attracting future investment and partnership with large pharmaceutical companies. This will be vital for the near-term growth of CCNTx, which will also lead to job creation in the Vancouver biotech ecosystem and training for highly qualified personnel.

Shaking in the Wings: Creating a Drama-based Curriculum Derived from Actor Education to Address Music Performance Anxiety

Objective of Project:

The intern will investigate how curriculum derived from actor education can be effective as an educational intervention on how in educating musicians to mitigate music performance anxiety without the use of pharmaceutical and psychological interventions. The full curriculum will consist of 42 hours of instructional material which will form the basis of a post-secondary course. This project consists of original research in a sub-field of music performance anxiety that is virtually non-existent (i.e., adapting acting education) and has the potential to solve a systemic issue that has a significant and negative impact on the health, wellbeing, and performance of most professional musicians.

To understand the nature of this work, it is important to discuss music performance anxiety and the negative impacts it has on musicians. Performance anxiety is a subcategory of social anxiety in the DSM-5 in Chapter 18 (DSM-5 Diagnostic Criteria for Social Anxiety Disorder). Music performance anxiety occurs when a performing musician experiences impaired thinking, adverse behavioural effects, and inconvenient physiological reactions (Steptoe, 2001). These debilitating impacts interfere with the performer’s body and delivery (Clark & Clark, 2002) (e.g., disrupt one’s breath) and control of instrument (Osborne & McPherson, 2019), also causing stress including shaking (Clarke et al., 2020), fainting (Kenny et al., 2016), and nausea (Boyett, 2019). In a survey, 98% of 447 professional musicians reported experiences of music performance anxiety (Beder, 2017). Musicians’ experiences may be explained by the systematic omission of music performance anxiety in school curriculum (Dobson, 2011; Bennett, 2007). The stakes of this omission are high. Substance abuse and thoughts of career abandonment are common responses to music performance anxiety (Orejudo et al., 2018). Most intervention methods to treat performance anxiety use pharmaceutical and psychological methods (Blair & van der Sluis, 2022), requiring specialist knowledge to facilitate, beyond the scope for most post-secondary teachers. Acting, as a therapeutic technique, an art form, and an experience, can be transformative—it is a powerful technique that changes the performer into a character and changes the story into an inspiring narrative free of anxiety.

The expected skills and competencies of the Intern include:

Skills:

research and writing skills: contribute to the curriculum on music performance anxiety by creating a curriculum handbook and contribute to scholarship by publishing in peer-reviewed journal articles (e.g., Music Education Research and Psychology of Music);
presentation skills: presenting the work at BC conferences (e.g., research conference at UBC in June 2025); and
teaching skills: teach BC-based workshops to musicians and teachers and provide copies of the curriculum handbook to better facilitate learning.

Competencies:

expand knowledge and expertise in music performance anxiety and adapt curriculum based on feedback from music professionals and researchers;
problem-solving: work to solve a system health issue prevalent among musicians in BC;
mobilize BC-based post-secondary teachers to support BC musicians in managing music performance anxiety (i.e., empower the community by creating resilience and tools in addressing mental health challenges, specifically music performance anxiety); and
catalyze change in the BC music community by using curriculum strategies that can be learned in accessible training workshops without the requirements of highly specialized experts and training in pharmacology and psychology.

How the project and internship will support the health organization:

This project supports the innovation and development of the organization’s core research and the creation of its research institute in providing expert advice and support to music institutions and the music community in the area of music performance anxiety. It takes a considerable amount of time and care to develop new curriculum, especially in a therapeutic discipline. The intern (PhD candidate) has an appropriate level of education and practical experience (teacher/performer) in creating suitable curriculum for this organization and pedagogies in addition to having experience working with vulnerable adults. The organization will benefit from having a fully developed manuscript containing the curriculum and pedagogies. The intern will be submitting this work to conferences and peer-review journals, which will help promote this organization’s credibility in leading new research and practical workshops to support the health and wellness of the BC music community. The organization supports the BC music community by presenting workshops for musicians to help reduce anxiety, and by having teacher workshops with methods for teachers to share with students. This project will decrease barriers for musicians with music performance anxiety in accessing BC jobs and reduce the impacts on the BC health care system (e.g., reduce anxiety symptoms which may contribution to a reduction in the use of anxiety medications by BC musicians, and potentially a reduction in psychological assessments and hospital visits). By reducing the impacts of music performance anxiety, this project helps BC musicians perform at a higher performance level with decreased anxiety. It is expected that BC musicians will be able to retain employment opportunities (e.g., fewer sick days and missed performance opportunities), suffer reduced job loss, and allow them to successfully compete for jobs at a local, domestic, and international level.

This project will help the organization in building instructional material for teaching, teacher training, and post-secondary workshop facilitation in post-secondary and music institutions. Several music schools and professional companies have expressed strong interest to the intern and organization in the need for wellness support for their musicians, including the Victoria Conservatory of Music, the University of Victoria, Pacific Opera Victoria, and the Friends of Music Society. In a survey of BC music schools, only one school responded that they have means of supporting students in managing music performance anxiety. There is a huge gap in health supports that is not being filled by other health organizations. The Victoria Conservatory of Music, for example, is currently seeking facilitators for wellness workshops to help support musicians in Victoria because of urgent wellness issues identified in the Victoria, BC based music community. This project fills a unique need because music schools and professional companies cannot administer pharmaceuticals to relieve symptoms of anxiety, nor can most schools afford to provide/hire professional psychologists to support students with anxiety. This research provides a viable alternative that administers acting therapy and not pharmaceuticals and psychological treatments. This organization also provides an intervention that offers a viable alternative to illicit street drugs which are rampant in BC. Substance use is a common response for musicians to deal with anxiety, and unfortunately the use of illegal drugs by musicians is an issue (Orejudo Hernández et al., 2018). Illegal drugs endanger a musician’s health and wellbeing; 14,400 people have lost their lives to opioids since the Province declared a public health emergency in 2016 (192 people in B.C. died, 2024). It is imperative that new ways to manage anxiety are introduced into the music field. The proposed work provides a viable alternative for musicians to manage music performance anxiety.

References

192 people in B.C. died due to toxic drugs in March: coroner. (2024, May 6) CBC. https://www.cbc.ca/news/canada/british-columbia/toxic-drug-deaths-march-2024-1.7196617
Beder, J. (2017). The 2015 musicians’ health survey results. Senza Sordino, 55(2). International Conference of Symphony and Opera Musicians. https://www.icsom.org/senzasordino/2017/06/ the-2015-musicians-health-survey-results/
Bennett, D. (2007). Utopia for music performance graduates. Is it achievable, and how should it be defined? British Journal of Music Education, 24(2), 179–189.
Blair, E., & van der Sluis, H. (2022). Music performance anxiety and higher education teaching: A systematic literature review. Journal of University Teaching & Learning Practice, 19(3). https://ro.uow.edu.au/jutlp/vol19/iss3/05/
Boyett, C. (2019). Music performance anxiety. MTNA e-Journal, 10(3), 2–21.
Clark, M. R., & Clark, L. V. (2002). Singing, acting, and movement in opera: A guide to singer-getics (1st ed., pp. 104–110). Indiana University Press.
Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). (2013). American Psychiatric Association.
Dobson, M. C. (2011). Insecurity, professional sociability, and alcohol: Young freelance musicians’ perspectives on work and life in the music profession. Psychology of Music, 39(2), 240–260. https://doi.org/10.1177/0305735610373562
Kenny, D. T., Arthey, S., & Abbass, A. (2016). Identifying attachment ruptures underlying severe music performance anxiety in a professional musician undertaking an assessment and trial therapy of intensive short-term dynamic psychotherapy (ISTDP) Springerplus, 5(1), 1–16. https://doi.org/ 10.1186/s40064-016-3268-0
Orejudo Hernández, S., Zarza-Alzugaray, F. J., & Casanova, O. (2018). Music performance anxiety. Substance use and career abandonment in Spanish music students. International Journal of Music Education, 36(3), 460–472. https://doi.org/10.1177/0255761418763903
Osborne, M. S., & McPherson, G.E. (2019). Precompetitive appraisal, performance anxiety and confidence in conservatorium musicians: A case for coping. Psychology of Music, 47(3), 451–462. https://doi.org/10.1177/0305735618755000
Steptoe, A. (2001). Negative emotions in music making: The problem of performance anxiety. In P. N. Juslin, & J. A. Sloboda (Eds.), Music and emotion: Theory and research (pp. 291–307). Oxford University Press.

The proposed novel passive hand tremor attenuator for Parkinson’s patients

Problem statement:

Parkinson’s disease is a condition that gradually affects the nervous system, primarily impacting movement. One of the earliest and most noticeable signs is shaking or tremors in the hands. These tremors might start off barely noticeable but can become more severe over time. As the disease progresses, people with Parkinson’s might find it harder to swallow, have trouble maintaining their balance, and experience a significant decrease in their ability to move freely. These challenges not only affect daily life but can also lead to other serious issues like falls and poor nutrition. Common treatments for Parkinson’s disease include medications, physical therapy, and sometimes surgery. However, these treatments don’t always effectively control hand tremors, especially in the early stages. This highlights the need for new and better ways to help people manage their symptoms and improve their quality of life.

Project Aims/Objectives:

Our study presents an innovative solution for reducing early-stage tremors by developing a special wearable device. This device uses magnetic technology to reduce shaking in the hands and arms. Magnetic actuators, which are small devices that control movement using magnets, help stabilize the hand and arm movements. The device is designed to be both effective and easy to use, making it suitable for daily wear by people with Parkinson’s. We will test this wearable device in various scenarios to see how well it works. We expect it to consistently performed better than other available options for reducing tremors. One of the best features of this device will be its light weight, only around 120 grams, which makes it much more comfortable to wear than heavier and existing devices. Its light weight ensures that it doesn’t add extra strain or discomfort, which is important for people who might wear it for long periods. The device is also designed with the user’s comfort and convenience in mind. It can be worn discreetly under clothes, so it doesn’t draw attention. It should be easy to put on and take off, which is crucial for those who might have difficulty with fine motor skills. This study introduces a promising new way to help manage all-stage tremors in Parkinson’s disease. The wearable device, with its advanced magnetic technology, offers an effective, lightweight, and user-friendly option for people looking to control their symptoms and improve their quality of life. Our initial tests show that this device could make a significant positive impact on the daily lives of those with Parkinson’s disease. Future research will aim to refine the device further, test its long-term effectiveness, and make it more widely available to those in need. The final objective of this project is human trials. Initial trials with patients will be conducted to evaluate the effectiveness of the hand tremor device. These trials will involve participants with Parkinson’s disease using the device in their daily routines. Researchers will closely monitor improvements in tremor control, user comfort, and overall usability. Feedback from these trials will be essential for refining the device and ensuring it meets the needs of those it is designed to help.

Skills/Competencies Development:

Designing a new device to help reduce hand tremors, especially for someone working at a postdoctoral level, requires a mix of many different skills. First, a strong understanding of mechanical engineering is important. This means knowing how things move and vibrate so the device can effectively reduce tremors. It’s also necessary to choose materials that are light, strong, and safe to use. Using computer software to design and test the device before making it is also a key skill. The intern needs to know how to use small magnetic devices to control movements. The intern skills are crucial for making sure the device is comfortable and easy to use for people with Parkinson’s disease. This includes understanding how the device interacts with the human body and ensuring it fits well. Prototyping and testing the device are key steps. This involves quickly creating models of the device, testing them to see how well they work, and making improvements based on those tests. Analyzing the data from these tests helps ensure the device is effective and reliable.

Managing the project effectively is important, too. This includes working well with a team of different experts, keeping the project on schedule, and documenting every step of the process clearly. Understanding the rules and regulations for medical devices is essential to ensure the device can be approved for use. This involves following strict guidelines to make sure the device is safe and works as intended. Focusing on the needs of the users is critical. This means conducting research to understand what people with Parkinson’s need, testing the device with real users, and making adjustments based on their feedback. Finally, strong communication skills are important. This includes writing clear documents and reports, and being able to present the device and its benefits to others, including potential investors and regulatory authorities. racking project expenses and providing regular progress reports are crucial responsibilities for the intern working on the hand tremor project. This involves maintaining detailed records of all costs related to materials, prototyping, testing, and other project activities. Regular progress reports will be created to update stakeholders on the project’s status, achievements, and any challenges faced. Patient trial coordination involves organizing small-scale trials in collaboration with a local clinic to test the hand tremor device. This includes recruiting participants, scheduling trial sessions, and ensuring all necessary medical and ethical approvals are in place. Working closely with the clinic staff, the intern will oversee the trials, collect data on the device’s performance, and gather feedback from patients. This collaboration aims to ensure the device is safe, effective, and ready for wider use.

Support to the Company:

The project and internship will bring substantial benefits to Summit Engineering Solutions in several key areas, positioning the company for significant advancements and market leadership. First and foremost, the project will facilitate the development of a novel hand tremor attenuator, a critical innovation for individuals suffering from Parkinson’s disease. Developing such a device is often financially challenging, especially for small-sized companies. By leveraging the resources and expertise provided through the project and internship, Summit Engineering Solutions can overcome these financial barriers. This collaboration allows the company to invest in cutting-edge technology and research that might otherwise be beyond its budgetary constraints, leading to the creation of a highly effective and marketable product.

Furthermore, this initiative will strengthen the collaboration between Summit Engineering Solutions and the Heart Valve Performance Laboratory (HVPL) at UBC’s Okanagan campus. This partnership is mutually beneficial, combining the university’s research capabilities and academic expertise with the company’s practical engineering and manufacturing experience. Such a relationship not only enhances the quality of the research and development process but also fosters an environment of innovation and knowledge exchange. By working closely with academic researchers and students, the company can stay at the forefront of technological advancements and emerging trends in the field of wearable medical devices. This collaboration will also position Summit Engineering Solutions as a leader in the Parkinson’s wearable device market, enhancing its reputation and opening up new opportunities for growth and investment. Additionally, the project will significantly accelerate the development timeline of the hand tremor attenuator. The internship program will provide additional manpower and expertise, enabling faster progress through the various stages of development, from initial design and prototyping to testing and final production. By speeding up the development process, Summit Engineering Solutions can bring the device to market more quickly, ensuring that patients in need can benefit from the new technology sooner.

Developing Xeno-Free Media for Scalable Production of Dermal Sheath Cells

Dermal Sheath Cells (DSc) show promising potential in regenerative medicine for their role in hair follicle regeneration and wound healing. However, their clinical use is hindered by challenges in scalable production. Microcarrier-based culture systems offer a solution, with microcarrier type and culture conditions crucial for optimizing cell yield, viability, and function.

In this project, our goals are twofold: firstly, transitioning from serum-based to serum-free media to enhance consistency, reduce costs, and eliminate contamination risks from animal-derived components. Secondly, using edible microcarriers made from plant-based resources to enable large-scale cultivation of DSc.

This internship will allow the intern (currently a visiting PhD student at the University of Victoria) to enhance their skills in:
– Advanced cell culture techniques, including microcarrier-based systems and serum-free media formulations.

Non-invasive gut mucus analysis to functionally characterize the effects of GEMM and afford new IBD biomarkers.

Inflammatory bowel disease (IBD) affects ca. 300,000 Canadians with an annual burden of $1.3 billion in associated with treatments, medications, and lost productivity. Accurate biomarkers are required to distinguish between IBD from conditions with similar symptoms, to ascertain disease aggressiveness, predict complications or recurrence, and to evaluate the effectiveness of therapeutic interventions. Currently, endoscopic procedures are the clinical “gold standard” in IBD monitoring/diagnosis, but the invasiveness and cost of these tests prevents their routine application. The urgent need for effective, routine, and non-invasive IBD biomarkers is underscored by statistics indicating that one-in-three IBD patients fail to respond to the initially selected treatment with half losing response over time. This Mitacs proposal seeks to develop an untapped source of IBD biomarkers: the complex carbohydrates (called glycans) that make up the thick layer of mucus that protects the human gut, regulating and reflecting both the microbiome and the immune system. Simple monosaccharides can be biochemically sequentially combined in different ways (analogously to Lego blocks) to produce diverse glycans that are linked to an invariant protein backbone. Glycomic analyses has revealed that mucus may be up to 80% glycan by mass and thousands of glycan representing hundreds of unique structures either provide a nutrient source for microbes or keep them at bay, accomplishing activities both in structure-dependent ways. Although dynamic, research has shown that changes in the entire population of mucus-linked glycans may predispose to spontaneous colitis while other specific glycans are well-known hallmarks of inflammation; thus, glycans are linked to the etiology of IBD as well as representing putative markers of disease activity. Promising technology—called Genetically Engineered Microbial Medicines (GEMM)—developed by our Mitacs Life Sciences partner company Melius Microbiomics (MMB), seeks to use novel probiotics to repair the compromised gut barrier in IBD patients. We propose that evaluating the impact of GEMM on the protective gut mucus-glycans represents an ideal opportunity to establish glycans as non-invasive IBD biomarkers using the new high-throughput tools being developed in the Zandberg lab. Importantly, our research has demonstrated that gut mucus can be non-invasively collected from clinical stool samples and productively subjected to glycomic analyses.

This project has three aims:

Characterize how the mucus-borne glycans change in animal IBD models in the presence or absence of GEMM and correlate these changes with IBD disease metrics.
Develop a high-throughput glycan analyzer using repurposed Sanger Sequencers.
Characterize the stool-derived mucus-glycans in a longitudinal set of neonatal samples and correlating changes in the glycan populations with the microbiome and markers of inflammation.

The three aims afford three benefits to partner organization:

Tissues and mucus collected as part of previous and also future GEMM trials will be characterized by existing glycan-analysis techniques, generating knowledge required to establish stool-derived mucus-glycans as IBD biomarkers. These molecular details will inform MBB of the effects of their products at the mucosal interface between the microbiome and immune systems. In the long-term, we envision that MBB could use mucus-glycan biomarkers to predict which IBD patients will most optimally respond to GEMM treatment as well as providing direct functional evidence of gut mucosal healing.
A major outcome of the proposed research is a mucus-glycan profiling tool that can be used by MMB, ideally onsite.
The knowledge generated from the analysis of neonatal samples will enable MBB to develop important new markets for GEMM. Specifically, no routine screening tool or effective prophylactic currently exists for diseases like necrotizing enterocolitis (NEC), the most common and destructive gut disease in preterm infants.

Skills developed by intern(s) during this project include proficiency in several major analytical instruments that are currently in high demand in both academia and industry as well as data analytics skills. MBB expertise in market development, clinical trials, and bioengineering will afford the intern(s) with unique insights in these activities that are not normally possible in academia.

In vivo testing of LNP-mRNA therapeutics in an animal model of Gaucher Disease

Brain diseases are the leading cause of disability and the second leading cause of death globally. Of the estimated 3.6 million Canadians suffering from a neurological disorder, 170,000 live in long-term care facilities, placing an enormous burden on patients, their families, and our health care system. This problem is expected to worsen with an aging population, underscoring an urgent need for new treatments in the brain.

We have extensive understanding of what causes most brain disorders, with many natural proteins being identified that hold significant therapeutic promise. One such example is Gaucher Disease (GD, Types I,II,III), a rare metabolic disorder caused by a deficiency in the vital enzyme Glucocerebrosidase (GCase). GD manifests as a spectrum of brain disease, from rapid neurodegeneration and death in infancy or early childhood (Type II), to saccade eye movements, epilepsy, or dementia (Type III). Even Type I, which is often considered ‘non-neuronopathic’, has been shown to be strongly linked with Parkinson’s disease and related neurological symptoms. Peripheral symptoms of GD Types I and III, such as anemia, reduced bone density, and splenomegaly, are treated with biweekly intravenous infusion of imiglucerase (Cerezyme®), an enzyme supplement for GCase, whereas Type II has no treatment. However, Imiglucerase has no impact on neurological symptoms in GD because it does not reach brain tissues. This is because protein therapeutics (and even most conventional small molecule drugs) cannot penetrate the protective blood brain barrier (BBB) that blocks most medicines from reaching the brain compartment.

To tackle this problem and bring new treatments to the central nervous system (CNS), our group has developed a technology that empowers the brain to produce its own therapeutic proteins. Using a technology similar to the COVID19 vaccine that combines lipid nanoparticles (LNP) and messenger RNA (mRNA), we can circumvent the BBB problem by transforming brain cells into protein factories that continually produce these therapeutic proteins over days to weeks, termed the brain ‘Bioreactor’ approach. This is a versatile technology with potential to target many brain disorders – by simply swapping mRNA cargos in pre-optimized LNP carriers, we can use the same subset of brain cells to produce different therapeutic proteins to target different diseases. We have proof of concept data in mice demonstrating this strategy is tunable and achieves long lasting brain-wide biodistribution of three different proteins (i.e. using three different mRNAs), requiring fewer infusions compared to existing treatments.

As an important validation of our LNP-mRNA platform, the proposed collaboration with the MacVicar Lab at UBC is to develop an LNP-RNA treatment for neuronopathic Gaucher Diseases (primarily Types II-III). We propose to use our Bioreactor strategy to manufacture GCase directly in the brain as a treatment of neuronopathic GD. Our group uses brain-optimized LNPs to achieve widespread LNP-mRNA uptake in support cells in the central nervous system to transform them into Bioreactor cells. These Bioreactor cells will translate the mRNA into functional GCase, which is released to the entire brain, from inside the BBB, to effectively replace the dysfunctional GCase that causes GD. An ongoing and complimentary project in the MacVicar Lab is generating new mRNA constructs for GCase and testing them in culture systems. These mRNAs are being engineered for improved stability for long-lasting GCase production prior to animal testing. The project proposed here will explore the therapeutic potential of our lead candidate GCase mRNA constructs in rodent models. The work will be comprised of three Aims:

to test for successful GCase expression in the CNS using candidate LNP-mRNAs in healthy mice and rats via direct brain and/or spinal cord injections;
to characterize GCase enzyme activity from LNP-mRNA injections compared to direct GCase protein injections (such as in enzyme replacement therapies); and
to test the therapeutic efficacy of LNP-mRNA in a mouse model of neuronopathic GD. The intern, Dr. Radisavljevic, recently completed her PhD in Biochemistry and Molecular Biology examining links between the gut microbiome and neurodegeneration with Dr. Brett Finlay at UBC. Her extensive expertise in molecular biology, neuroscience, and rodent disease models makes her ideally suited for this project.

Dr. MacVicar has over 40 years of experience as a neuroscientist with a proven track record of training young scientists that go on to faculty positions in academia, medicine, industry, and government agencies. Dr. Radisavljevic will work closely with neuroscientists in the MacVicar laboratory, where she will further develop expertise in the field, including technical training on rodent brain surgeries and injections, and state-of-the-art laser microscopes and image analyses. Dr. Radisavljevic will also be directly involved in training and mentoring students in the lab to further develop her leadership skills. Dr. MacVicar’s ongoing collaborations with Dr. Pieter Cullis, a world leader in LNP-based nanomedicines, will position Dr. Radisavljevic at the forefront of next-generation therapeutic development, with access to UBC’s vast network of RNA and nanomedicines experts and ability to produce high quality research. Dr. Radisavljevic will also be exposed to a breadth of training opportunities at CCNTx that would only be possible at a small startup company. Dr. Radisavljevic will be directly involved in higher-level R&D and IP planning related to CCNTx operations. This will include participating in IP strategy, forward-looking research objectives, business development activities, and attending industry conferences. This will place Dr. Radisavljevic in a position to contribute both to the R&D and the growth of the company during its formative stages.

The effects of isocapnic respiratory muscle endurance training on the multidimensional components and neurophysiological mechanisms of exertional breathlessness in healthy adults

Unsatisfied inspiration is a sensory experience where individuals feel like they are not getting enough air into their lungs. This sensation is highly prevalent in patients with chronic lung disease due to pathological mechanical constraints on lung expansion. These constraints can compromise exercise tolerance and lead to negative emotional and behavioural responses to physical activity. Traditionally, this sensation has been considered relatively absent in healthy individuals. However, recent work by Ferguson et al., (2024) (the application intern) revealed that 34% of young, healthy participants reported experiencing unsatisfied inspiration. These findings further suggested that constraints on inspiration may be the predominant physiological driver of this distressing breathing sensation in young healthy adults. Additionally, the unsatisfied inspiration group had a significantly higher selection frequency of “breathing” being their primary limitation at the end of the exercise. Although the underlying cause of this physiological constraint remains unclear it is plausible that these individuals may display an unconventional breathing pattern (i.e., rate and depth), coordination, or an inability to maintain optimal breathing techniques throughout longer bouts of exercise.

Respiratory muscle training may have the potential to alleviate this sensation of unsatisfied inspiration and improve performance. Specifically, isocapnic training allows individuals to breathe as hard and fast as they need to sufficiently train their respiratory system while maintaining constant carbon dioxide levels. This training modality may help individuals target the respiratory system by aiding in the development of breathing techniques which optimize respiratory muscle coordination and power, and subsequently reduce the distressing sensation of breathlessness. Moreover, respiratory endurance training may also contribute to the desensitization of the individual to higher exercise ventilations, which may in turn contribute to a reduced perception of breathlessness. However, previous research has largely focused on resistive breathing training devices, which resulted in contradicting findings on exercise performance. One device, the Spiro-Tiger has attempted to provide a device capable of addressing respiratory endurance rather than strength, however, the complexity and cost of this product hindered its growth in the North American market.

The Isocapnic BreathWayBetter (BWB) (Isocapnic Technologies Inc, Kelowna, Canada) is a commercially available, affordable, portable device, paired with the free user-friendly app that allows for personalized training programs with visual guidance that can be performed anywhere. However, its efficacy in improving measures of perceptual responses, such as unsatisfied inspiration following a prolonged training regimen remains relatively unknown. Therefore, the primary aim of this study is to investigate the effects of 5 weeks of respiratory endurance training with the BWB device on the multidimensional components of breathlessness (e.g., immediate perception and emotional/behavioural aspects). Additionally, we aim to elucidate the physiological measures associated with reductions in these perceptual measures, through a comprehensive assessment of respiratory mechanics and muscle activation patterns, as well as operational lung volumes.

This research being done into the effectiveness of targeted respiratory training with subjects identified with unsatisfied inspiration will have great benefit to the company as it expands its user base, and increases awareness of the effectiveness of their product and training methodologies. Olivia (intern) will gain new skills by working with an industry partner to better understand how her current research skills can inform the development of effective medical devices. Additionally, this work will complement her previous research in exercise and breathlessness, providing hands-on experience in testing the efficacy of a medical device on breathlessness and respiratory physiology. Lastly, gaining experience working in industry will be an invaluable asset as she moves forward in her research career.