In a recently published preclinical study, Dr. Isabelle Aubert, senior scientist at Sunnybrook Research Institute and postdoctoral researcher Dr. Kristiana Xhima successfully used focused ultrasound to non-invasively deliver a therapeutic in the brain, targeting brain cells affected by Alzheimer’s disease and improving cognition.

The study has been published in the journal BRAIN.

This is the first study to demonstrate that repeated focused ultrasound blood-brain barrier modulation in the basal forebrain is safe in the presence of Alzheimer’s pathology, and when combined with a growth factor-related therapeutic, can lead to therapeutic effects. Focused ultrasound harnesses the power of sound waves to transiently open the blood-brain barrier, a protective barrier that prevents toxins or potentially helpful therapeutics in the bloodstream from entering the brain.

This promising research comes at an urgent time. It is estimated that more than 600,000 Canadians are currently living with dementia. According to a recent report from the Alzheimer’s Society of Canada, rates of dementia, including Alzheimer’s disease, are projected to rise to nearly 1 million people in Canada by 2030. Below, Drs. Aubert and Xhima discuss how their breakthrough research is an important advancement on the road to developing effective therapeutic approaches for the disease.

Dr. Aubert and Dr. Xhima

What was the impetus behind your study?

Dr. Aubert: This preclinical study was a follow-up to our previous proof-of-concept study that used MRI-guided focused ultrasound to non-invasively deliver a type of growth factor-related therapeutic (D3) to brain cells called cholinergic neurons, which are important for learning and memory and most vulnerable in Alzheimer’s disease. D3 stimulates important signaling mechanisms in brain cells that are related to the tropomyosin receptor kinase A (TrkA) pathway. The TrkA pathway is critical for neuroprotection, plasticity and survival of cholinergic neurons; engaging it with D3 promotes the resilience of brain cells against Alzheimer’s pathology.

In our first proof-of-concept study, we had found that D3 combined with focused ultrasound efficiently stimulated key survival and neuroprotective pathways, and in the short-term, helped to restore brain cell communication (also known as neurotransmission). Yet for clinical translation and impact, it was critical for us to study whether focused ultrasound combined with D3 could rescue cognitive function – the rationale and goal of the current study.

What did your current study find?

Dr. Xhima: In this preclinical study, we demonstrated the therapeutic potential of D3 in a preclinical model of Alzheimer’s and showed its impact on learning, memory and cognitive flexibility. The D3 therapeutic agent, like many promising therapeutics, does not have the properties required to efficiently cross the blood-brain barrier (BBB) and reach its targets deep in the brain. To overcome this challenge, we coupled the intravenous administration of the therapeutic drug D3 with MR-guided focused ultrasound to non-invasively, locally and transiently increase BBB permeability in key brain regions for the effective delivery of D3 from the blood to the brain.

Following brain delivery of the therapeutic agent with focused ultrasound, performance in cognitive tasks was improved. The treatment of focused ultrasound with the therapeutic D3 led to enhanced neurotransmission in cholinergic neurons, which are highly vulnerable to injury in Alzheimer’s disease. We also observed beneficial effects on brain regeneration – new brain cells were formed in the hippocampus, an area of the brain that plays a major role in learning and memory, and amyloid plaques, common in Alzheimer’s, were reduced in targeted brain areas.

What could these results mean for patients and clinicians in the future?

Dr. Aubert: Although still early-stage, this work is an important and fundamental step in the development of potential treatments for the disease. The results also open the door for many other regenerative agents, that normally do not cross the BBB, to be tested and delivered using this drug-delivery platform. This is the first study to demonstrate that a growth-factor related agent delivered to the basal forebrain and associated cortical and hippocampal areas repeatedly using focused ultrasound BBB modulation is safe and can lead to therapeutic effects in the presence of Alzheimer’s pathology. These results provide a major step forward in terms of drug delivery that can be very promising for clinical translation.

Dr. Xhima: Another key feature of this preclinical research is that we tested focused ultrasound delivery of a TrkA-stimulating agent in the presence of established Alzheimer’s pathology. In contrast to many previous studies, here we showed that this therapeutic approach rescued cognition and improved Alzheimer’s related pathologies once they were already established, similar to how patients would present in the clinic. The beneficial effects of the treatment were also broad with respect to several key systems affected in Alzheimer’s disease. This makes us very hopeful about this therapeutic approach because it certainly represents an important step forward for potential clinical development.

What’s the next step in this work?

Dr. Xhima: The improvements in cognitive function we saw in the preclinical models studied lasted for several weeks, which raises the question: how often will treatment need to be repeated for therapeutic effects that can last over months and years?

Dr. Aubert: In addition to this, we’re interested in taking an exploratory approach to look at other molecular pathways in the brain that could also be affected by this treatment, since our results went beyond what was expected with target engagement on cholinergic neurons alone.

It’s important to note that this research is still at an early stage and has not yet moved to clinical trials. We are hopeful that this fundamental research will translate into the clinic in the near future, as we continue to explore therapeutic options to stop degeneration and promote regeneration in Alzheimer’s disease and dementia.

Hear Dr. Aubert and Dr. Xhima discuss their findings in further scientific detail on the BRAIN podcast, the official podcast of Brain and Brain Communications.

The post Behind the research: New study finds focused ultrasound enhances delivery of brain therapeutic and improves cognition in Alzheimer’s appeared first on Your Health Matters.

Despite the statistics, innovative research is underway at Sunnybrook to help bring hope to the fight against Alzheimer’s and dementia.

“We may be entering a new era with possible effective treatments for this disorder which affects whole families and is increasingly prevalent with populations aging,” says Dr. Sandra Black, director of the Dr. Sandra Black Centre for Brain Resilience and Recovery. “Continued research is critical as we aim to develop and discover meaningful treatments and prevention strategies for Alzheimer’s and dementia.”

Here are just some of the innovative ways that Sunnybrook clinicians and researchers are on the leading edge of research in the detection, prevention, and treatment of Alzheimer’s and dementia.

Apathy and Agitation in Alzheimer’s

At Sunnybrook, clinical studies are underway on apathy and agitation in Alzheimer’s patients, where researchers are exploring ways to help decrease apathy in patients. This can help increase their interest in activities and their emotional responsiveness, which may help improve their quality of life, as well as their caregivers’.

Early on-set dementia

In a world-first study, a team of Sunnybrook scientists are trying to identify biomarkers, or biological clues in the brain, such as blood flow, that could demonstrate an early-onset frontotemporal dementia in people who have a genetic predisposition to the disease.

 

View this post on Instagram

 

A post shared by Sunnybrook Hospital (@sunnybrook)

Innovative technology

Researchers are also looking for innovative ways to deliver medicine or therapeutics directly to the areas of the brain involved in Alzheimer’s disease.

Preclinical research is exploring the delivery of gene therapy to treat Alzheimer’s and help improve memory and boost brain health.

One of those methods uses focused ultrasound technology, where ultrasound waves are precisely directed to a targeted area of the brain to help open the blood-brain barrier (BBB), which can allow potentially helpful medications to reach brain regions involved in Alzheimer’s and dementia, without having to use scalpels. Research teams have shown evidence that the BBB can be temporarily opened safely using focused ultrasound, an exciting first step in exploring a new way for therapeutics to be delivered to the brain.

Who will get Alzheimer’s disease?

Sunnybrook scientists are also using artificial intelligence and machine learning to try and detect early signs and symptoms of dementia to improve treatment and prevention of the disease.

Research is also underway to learn more about risk factors for dementia among diverse ethnic groups including individuals of South Asian and Chinese descent, as these groups are often under-represented in dementia studies.

The latest Sunnybrook research has also demonstrated that having poor vascular health may accelerate cognitive decline in patients with dementia and small vessel disease.

Preventing Alzheimer’s

Researchers are finding out how lifestyle can protect individuals from dementia.

While it is critical for cutting edge studies to continue in the search for new treatment and care for patients with Alzheimer’s and dementia, it can also be helpful for individuals to take action themselves to learn more about dementia and how activity can help boost brain health in more ways than one.

From prevention to diagnostics and potential treatment innovations, “We’re at the forefront of discovery for dementia and Alzheimer’s at Sunnybrook,” says Dr. Black. “There’s a lot to be optimistic about.”

The post Advancing Alzheimer’s research appeared first on Your Health Matters.

Dr. Lesley Gotlib Conn

As a medical anthropologist working at one of Canada’s busiest hospitals, Dr. Lesley Gotlib Conn examines important aspects of health care delivery like communication and care transitions, and uses theories and methods from her anthropological training to improve care experiences and outcomes for patients, families, and health-care providers. She also examines the experiences and perceptions of trainees.

“We recently published the results of a study examining North American surgical residents’ attitudes toward the educational value of caring for injured older adults,” says Dr. Gotlib Conn, an associate scientist in the Tory Trauma Research Program at Sunnybrook Research Institute and Associate Director of SHARE. “A major finding of the research was that trainees reported less interest in learning about geriatric trauma care as they progressed through their training. This has important implications for the future of surgical training and care, since surgeons will be increasingly needed to treat the growing population of injured older adults.”

Dr. Gotlib Conn first became interested in education research while working on her PhD which explored the social construction of gender and sexuality in a psychiatric teaching clinic. Her research explored, in part, how learners and trainees in the clinic were socialized to think about gender and sexuality in medical ways. “The study of doctors’ and health professionals’ socialization has a long history in anthropology and sociology and that is what drew me into the field of education research,” says Dr. Gotlib Conn.

Now in her tenth year as a scientist at Sunnybrook, Dr. Gotlib Conn is proud to be advancing education research with SHARE. “At Sunnybrook we are fortunate to have a diverse and highly collaborative group of education researchers who are focused on understanding and improving learning, teaching and clinical training across many health professions. Every year I am more and more impressed by the caliber of the education research that is proposed to our grant competition and presented during rounds and at our annual symposium.” 

Dr. Giovanna Sirianni

As a family physician with a focused practice in palliative care, empathy is a core competency for Dr. Giovanna Sirianni.

Among her many education research interests, she is particularly focused on developing communication skills and the provision of compassionate care, which is in part why she co-created the About Empathy podcast, a healthCARE podcast that focuses on patient, caregiver and health-care provider stories.

“Podcast guests discuss their personal stories, while myself and my co-hosts reflect on those stories to help enable and support empathic interactions in the health-care community,” says Dr. Sirianni. “Our team has undertaken a qualitative exploration of the podcast’s role in education from the perspective of medical students, residents and faculty members.”

The podcast’s role in medical education is just one of many projects Dr. Sirianni is working on at any given time. “Whenever I’m developing a new curricular intervention, assessment method or project, I try to approach each initiative through a scholarly lens to help question, evaluate and eventually disseminate,” says Dr. Sirianni, who is also an Assistant Professor and Enhanced Skills Residency Program Director in the Department of Family and Community Medicine in the Temerty Faculty of Medicine at the University of Toronto.

Her passion for education research is inspired by many of the physicians, teachers and scientists she’s had the opportunity to work with throughout her career. “They modeled the importance of asking provocative questions about our approach to medical education and not accepting the status quo,” says Dr. Sirianni. “They also helped demystify the world of academia and made it accessible for me to feel like I had a place in education research too.”

Dr. Sirianni says that spirit is supported at Sunnybrook, in particular through Sunnybrook’s Education Advisory Council, via their yearly grant program that funds education research projects. “This is a tangible and practical way that we recognize and move forward the work of educators, scholars and researchers.”

The post Get to know SHARE: Meet two Sunnybrook education researchers appeared first on Your Health Matters.

A new study, published this week, from Sunnybrook senior scientist Dr. Donald Redelmeier explores how an available simple diagnosis can skew complex medical decision making.

“Occam’s razor is the traditional idea that simple explanations should be preferred over more convoluted theories,” says Dr. Redelmeier, who is also a Sunnybrook staff physician and Canada Research Chair in Medical Decision Making. “Yet this idea has rarely been subjected to experimental testing for evidence-based medicine.”

Dr. Redelmeier and his co-author Dr. Eldar Shafir from Princeton University were interested in testing the concept in the context of the COVID-19 pandemic. “We hypothesized that an available alternative explanation might lead individuals to underestimate the likelihood of a COVID-19 diagnosis,” says Dr. Redelmeier.

The study asked community members and health-care professionals to judge the chances of COVID-19 in a hypothetical patient through a set of different surveys. Each survey provided a succinct description of a hypothetical patient scenario, suggestive of COVID-19. Each scenario was formulated in two versions randomized to participants, differing only in whether an alternative diagnosis was present or absent.

“Through scenarios involving a spectrum of risk, we found that respondents judged the probability of COVID to be much lower in the presence of another diagnosis, such as influenza or strep throat, compared with when an alternative diagnosis was absent,” says Dr. Redelmeier. This contradicts available microbiological evidence.

“The bias can lead individuals to mistakenly lower their judged likelihood of COVID or another disease when an alternate diagnosis is present. In turn, underestimating the risk of COVID infection might reduce a patient’s willingness to seek care and a clinician’s willingness to investigate a medical diagnosis.”

Dr. Redelmeier adds that the results suggest an available simple diagnosis can lead to premature closure and a failure to fully consider additional serious diseases.

“This bias occurs because risk factors such as crowded living spaces, lapses in hand hygiene, and poverty are risk factors for COVID infection, as well as for other diseases such tuberculosis. After diagnosing a patient with COVID, for example, a clinician might pause and check — is that really everything?”

He adds that as patients are living longer with multiple diagnoses occurring together, an over-reliance on Occam’s razor can contribute to misplaced complacency and discourages the search for additional contributing factors.

“The bias may be important to recognize for the COVID-19 pandemic, other diseases, and for the next disease outbreak.”

The post Can an easy excuse lead people to underestimate a COVID-19 diagnosis? appeared first on Your Health Matters.

“The main theme of both studies is that people who have both Alzheimer’s disease and poor vascular health decline much more quickly than people who have only one of these conditions,” says Dr. Rabin, a scientist at SRI in the Hurvitz Brain Sciences Program.

There is growing evidence that vascular health and Alzheimer’s disease are closely intertwined, and that poor vascular health may promote the build-up of amyloid and tau in the brain, the two abnormal proteins associated with Alzheimer’s disease. “Preventing vascular disease may also help to prevent Alzheimer’s disease,” says Dr. Rabin.

The findings of the first study were published in Brain and the results of the second study were published in Neurology. Both are highly prestigious journals. Dr. Rabin, who was the only Canadian researcher involved in the studies, collaborated with U.S. colleagues to conduct the research.

Scientist Dr. Jennifer Rabin

What did you learn about the connection between CAA and Alzheimer’s disease?

The Brain study looked at a cerebrovascular condition known as cerebral amyloid angiopathy (CAA), which results from the build-up of amyloid in the blood vessel walls of the brain. When there is accumulating amyloid in the vessel walls it can cause vascular brain changes, such as small hemorrhages and blood flow problems. Although amyloid plays a central role in both CAA and Alzheimer’s disease, the two conditions are considered distinct.

The study is titled, “Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline.”

Dr. Rabin and colleagues from multiple U.S. centres asked the question: What influence does CAA have on the build-up of tau (the more detrimental hallmark pathology of Alzheimer’s disease) and cognitive decline, either alone or in combination with amyloid burden?

They analysed data from 1,722 autopsied subjects recruited from one of three long-running medical studies. Data included annual clinical and cognitive evaluations, along with neuropathology. The researchers tested associations between CAA, tau burden and cognitive decline, both independently and together with amyloid burden.

They found that the combination of CAA and higher amyloid levels were associated with the greatest tau burden and the fastest rates of cognitive decline.

“Not everyone with CAA has Alzheimer’s disease and not everyone with Alzheimer’s disease has CAA. But they do co-occur at a high rate,” says Dr. Rabin. “We found that if you have both of these conditions, you were much more likely to have tau burden and faster cognitive decline.”

How do classic vascular risk factors affect the brain?

The study in Neurology looked at whether classic vascular risk factors, such as obesity, high blood pressure, smoking and diabetes, leads to faster brain tissue loss and faster cognitive decline when they co-occur with amyloid.

The study is titled “Association of β-Amyloid and Vascular Risk on Longitudinal Patterns of Brain Atrophy.”

Dr. Rabin and colleagues from Massachusetts General Hospital analysed clinical and neuroimaging data from 196 subjects in the Harvard Aging Brain Study, a long-standing, community-based study.

They found that people who had multiple vascular risk factors and high levels of amyloid had greater rates of brain tissue loss and cognitive decline over time. “The take away,” says Dr. Rabin, “is that managing vascular risk factors may slow the progression of Alzheimer’s disease dementia.” This includes controlling blood pressure, lowering cholesterol, maintaining a healthy weight, and refraining from smoking. A good rule of thumb is that what’s good for the heart is good for the brain.

What do these results mean for patients and care providers?

These two studies provide greater support for the idea that vascular health and Alzheimer’s disease interact in ways that increase the likelihood of a dementia diagnosis. “These findings have implications for developing treatments for Alzheimer’s disease,” says Dr. Rabin, “because they suggest that vascular health should be taken into account. Treatments that target poor vascular health and Alzheimer’s pathology are likely to be the most effective.”

How you can get involved

If you are interested in getting involved in Dr. Rabin’s research studies, please send an email to cbhlab@sunnybrook.ca.

The post Behind the research: Studies provide more evidence that poor vascular health speeds up cognitive decline in Alzheimer’s disease appeared first on Your Health Matters.

When a person has ventricular tachycardia, faulty electrical signals in the ventricles of the heart cause their heart to beat too fast or irregularly, impeding proper blood flow to the body. “This is a very urgent problem,” says Dr. Fumin Guo, a postdoctoral fellow working in the cardiovascular imaging lab of Dr. Graham Wright at SRI. “Most of these events occur, without previous symptoms, at home or in a public space, not in hospital. And they can be fatal within minutes. We are trying to improve diagnosis and therapy to prevent sudden cardiac death.”

One of the current treatments for ventricular tachycardia is radiofrequency ablation, which involves guiding a device into the heart and using an electrical current to heat up and destroy a small area of tissue that may lead to the abnormal electrical signals (arrhythmia). But about 35 per cent of ablation procedures result in either initial failure or later recurrence.

Preclinical work by Dr. Guo and others in Dr. Wright’s lab is focused on improving the outlook for those with VT in three ways: identifying the underlying structural and functional issues in the hearts of individuals, pinpointing damaged tissue with greater precision, and delivering treatment with more accuracy and efficiency.

The lab has demonstrated success using 3D magnetic resonance imaging (MRI) to guide radiofrequency ablations with improved precision. “Imaging, and in particular MRI, shows great promise in helping to improve management in this patient population, and we are working at the state of the art to look at all aspects from identifying those at risk, to improving the effectiveness of procedures,” says Dr. Wright, who is a senior scientist in the Physical Sciences Platform and Schulich Heart Research Program at SRI.

Dr. Guo recently won the prestigious Polanyi Prize in Physiology and Medicine for his significant contribution to this work. With his background in biomedical engineering, he is developing, using artificial intelligence and computer vision methods, automated image analysis systems that map the heart and pinpoint the damaged tissue. He is also advancing computer algorithms to plan, guide and assess VT treatment.

“Fumin’s work means the image analysis needed to guide procedures will be more repeatable, faster, and hopefully more accessible to others,” says Dr. Wright. “The Polanyi Prize is very prestigious. Winning the prize is emblematic of the clinical relevance of the work and the excellence of Sunnybrook’s program in image-guided, personalized, precision therapy.”

Dr. Wright adds that his lab is collaborating with clinical heart programs and partnering with industry to ensure the preclinical work can be translated to patient care as quickly as possible.

For his part, Dr. Guo is enthusiastic about what lies ahead. “Our ultimate objective is to cure patients with ventricular tachycardia conditions. We want patients to live longer, healthier and happier.”

The post Scientists advancing research to prevent sudden cardiac death appeared first on Your Health Matters.

“Since the onset of the COVID-19 pandemic, Sunnybrook researchers have been quick to rise to the challenge, initiating more than 100 research studies related to COVID-19 that seek to make a substantive impact in better understanding the virus or proposing solutions to the many questions posed by the pandemic,” says Dr. Kullervo Hynynen, PhD, vice-president of research and innovation at Sunnybrook.

These studies were launched thanks in large part to donor support. Close to 11,500 donors from the community stepped up to help Sunnybrook’s COVID-19 response, contributing more than $7-million.

While insights into the virus are still evolving, it appears that although COVID-19 is best known as a respiratory disease, it also has repercussions elsewhere in the body. Here is a look at some of the research projects ongoing at Sunnybrook:

What impact does COVID-19 have on mental health?

Having seen the effects of the pandemic on mental health firsthand, Dr. Anthony Levitt, chief of the Hurvitz Brain Sciences Program and medical director of the Family Navigation Project (FNP), was spurred to lead a formal study into its wide-ranging impact, with the FNP team.

“I do not think we yet fully understand the tremendous negative, and even positive, impact of the pandemic on the mental health of our society,” Dr. Levitt says. “Our study is designed to explore this and the specific effects of having contracted COVID on mental illness and addiction.”

At the end of the project, around 7,500 Ontarians will have been surveyed over a period of a year and a half. Early findings have revealed that people who have contracted COVID-19 are at a greater risk of having depression, anxiety and substance misuse, compared to those who have not. As well, the data shows that several factors are associated with higher risk of suicidal ideation during the pandemic, including younger age, COVID-19 exposure and reduced socio-economic status.

The study has revealed that greater long-term social support is potentially protective of people experiencing these kinds of challenges, says Dr. Levitt. He hopes the study’s results will assist the province in creating better supports for people experiencing mental health challenges not only from the COVID-19 pandemic, but also for future pandemics.

What is the impact of COVID-19 on the brain?

Neuroscientist Dr. Simon Graham, PhD, is leading a team looking at the longer-term cognitive effects of infection. “The brain effects of COVID-19 are somewhat under-appreciated, and we don’t know the full extent to which they’re occurring,” he says.

Using magnetic resonance imaging (MRI) and behavioural assessments, Dr. Graham’s study has already shown some patients who were on a ventilator before recovering suffered from brain micro-bleeds or mini-hemorrhagic strokes. Some recovered patients have also been found to have evidence of inflammation in the brain.

These discoveries are particularly important given the growing number of “long haulers,” patients who experience lingering problems from the virus like brain fog and poor memory, Dr. Graham adds.

“Even if their persistent symptoms have to do with shortness of breath or abnormal heart rate, those things are actually controlled by the brain, so it could be COVID-19’s impact on the brain is causing those problems, too.”

What is the relationship between COVID-19 and the heart?

Cardiologist Dr. Idan Roifman in the Schulich Heart Research Program at Sunnybrook is leading research examining how COVID-19 may lead to inflammation of the heart muscle or cause damage to the heart similar to a heart attack.

The study is building on considerable research globally showing COVID-19 increases the risk of blood clots.

Using magnetic resonance imaging (MRI), Dr. Roifman’s work seeks to find evidence of heart damage in patients who have recovered from COVID-19 and determine the type of damage that has occurred. The study is also investigating how risk factors like diabetes and high blood pressure may elevate the risk of developing cardiac complications like heart failure.

Already, the research has revealed heart function abnormalities in some patients in recovery. “That alerted us to follow them closely and led to a potential change in their long-term management,” Dr. Roifman says.

Why do COVID-19 symptoms persist in some people?

Sunnybrook’s Dr. Hubert Tsui, head of hematopathology, and clinical microbiologist Dr. Robert Kozak, PhD, are poring over blood tests and nasal swabs from patients with COVID-19 to understand why some individuals become so-called long haulers. “The research literature states as much as 50 per cent of people could have some long-term COVID symptoms,” says Dr. Tsui.

The researchers have been looking at early diagnostics from patients who became long haulers, while comparing them with other patients who have fully recovered to see if they have a different initial immune system response. “Some of our preliminary data is indeed showing that something very early on, even at the diagnostic point, is different – providing a clue in terms of risk to developing long COVID,” he adds.

Understanding the basic science regarding immune response to COVID-19 could lead to identifying patients who are likely to experience long-term problems early on, Dr. Kozak notes. Research could even lead to therapeutics to prevent and treat long-hauler symptoms.

“The more we can help people now, the more they will benefit down the road,” he says.

The post Sunnybrook community steps up to support critical COVID-19 research appeared first on Your Health Matters.

Dr. Rikke Kofoed and Dr. Isabelle Aubert

In a new study, postdoctoral researcher Dr. Rikke Kofoed and senior scientist Dr. Isabelle Aubert and their team at Sunnybrook Research Institute determined the feasibility and safety of two noninvasive methods for delivering gene therapy to the brain in a preclinical model of Alzheimer’s disease.

The study has been published in Molecular Therapy – Methods & Clinical Development.

Alzheimer’s disease is the most common form of dementia, which impacts more than 430,000 Canadians aged 65 years and older. Hallmarks of the neurodegenerative disease include “plaques” and “tangles” composed of toxic protein that develop in the brain and eventually prevent the production of nutrients and the transmission of signals that are necessary for the health of brain cells. Over time, this causes deficits in cell-to-cell communication and functions, leading to memory loss, confusion and difficulty reasoning. There is currently no effective treatment for the disease.

Researchers at Sunnybrook are interested in gene therapy as a potential treatment for Alzheimer’s disease and other disorders of the brain. Gene therapy can replace a gene that is missing or defective. Specific genes can also be added to allow brain cells to stay healthy, produce therapeutics, or generate new cells to curb the disease.

Although gene therapy shows promise in Alzheimer’s disease, the blood-brain barrier poses a challenge for delivering it to the brain. In this study, the research team evaluated two innovative methods to non-invasively deliver gene therapy across the blood-brain barrier: a) focused ultrasound combined with intravenous microbubbles, which increase the permeability of the blood-brain barrier at targeted sites, and b) modified gene carriers, which are capable of crossing the blood-brain barrier and delivering genes to brain cells.

Dr. Kofoed and Dr. Aubert share thoughts on their research.

Dr. Rikke Kofoed in the lab

What did your study find?

Dr. Kofoed: In this preclinical study, we found that depending on which delivery method is used (focused ultrasound or modified gene carriers), a unique distribution of genes is seen in the brain. These findings tell us that in the future, gene therapy can likely be tailored to achieve personalized deliveries of genes depending on disease stage and the type of therapeutic gene.

We also determined that these non-invasive delivery methods have a good safety profile and that the immune response triggered is similar to what is seen after gene delivery using brain surgery. Our findings suggest that the immune response to non-invasive gene delivery can be controlled, as it is currently done in the clinic for other gene therapy approaches.

What could these results mean for patients in the future?

Dr. Aubert: In the past, the delivery of therapeutic genes required invasive surgeries for patients with Alzheimer’s disease. ​Non-invasive and personalized gene delivery to the brain has the potential to increase beneficial clinical effects for the treatment of Alzheimer’s disease. Our preclinical study confirms that focused ultrasound and modified gene carriers are feasible strategies for gene delivery to the brain, and that their immunological effects can be controlled.

What’s next in this research?

Dr. Kofoed: In this study, we used an easily visible “reporter” gene to explore the potency of gene delivery. The next stage of our research will look to deliver a therapeutic gene to target Alzheimer-related pathology in a preclinical model. These studies will help us determine the therapeutic potential of our delivery strategy.

Dr. Aubert: Gene therapy has tremendous potential for the treatments of brain disorders. The current study and the next stage of our research are required steps to evaluate the safety and efficacy of gene therapy approaches. With colleagues and collaborators at Sunnybrook and other institutions, these approaches could one day be brought to patients to halt degeneration and promote brain health for conditions such as Alzheimer’s disease.

Key drivers of Sunnybrook’s research are funding agencies and philanthropic investment. This study was funded with support from the Alzheimer Society Research Program, the Carlsberg Internationalisation Fellowship, the Canada Research Chairs Program, Canadian Institutes for Health Research (CIHR), the Weston Brain Institute, the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health and Temerty Chair in Focused Ultrasound Research. Additional funding was received from the FDC Foundation, the WB Family Foundation and Gerald and Carla Connor.

The post Behind the research: Study explores delivery of gene therapy to treat Alzheimer’s appeared first on Your Health Matters.

Below, a few members of the REB provide an inside look at the work done by the committee and share why they choose to provide their time to further research.

What are the responsibilities of the REB?

Dr. Jordan Tarshis (anaesthesiologist and REB scientific member, Sunnybrook)

The two primary goals of the REB are to protect human participants in research trials and facilitate and promote clinical research at Sunnybrook. The REB is always looking to optimize the safety of participants in research, which includes medical care as well as privacy and security. Once the REB receives a proposed project from the study team, we review it and often suggest modifications to the proposal to improve the safety and privacy of participants, while maintaining the integrity of the research proposal.

Our role as an REB was recently summed up nicely by the REB chair, Dr. Brian Murray, who said we are here not to protect the participants from research but to protect them for research.

Who serves on the REB?

Tiffany Tassopoulos (manager, research ethics, Sunnybrook)

The members of the REB are unpaid volunteers — health-care professionals, researchers, lawyers and community members — who genuinely want to give back to patients and support research by providing their time and expertise. The team is led by our incredible chair and vice-chair, Dr. Brian Murray and Lisa Di Prospero, Keitha McMurray (executive director, research integrity & clinical research services), myself and the dedicated staff in the research ethics office (Catherine Parry and Monica Hung).

I often say the REB is one of the hardest working committees at Sunnybrook. The collective effort of this committee is humbling. These individuals receive little to no recognition and are often unknown to the researchers, staff and patients that take part in research, and yet play such a critical role in the clinical research process.

What are some of the benefits of volunteering with the Sunnybrook REB?

Dale Philp (REB legal, privacy and community member)

Volunteering with the REB provides an opportunity to give back and to learn about new and exciting research. Personally, I was looking for an opportunity that would allow me to give back to the community and, after retiring from 28 years of practicing law, I wanted to continue using my skills into retirement. I’ve been part of the REB for three years (a typical term) and I’ve found the experience humbling. It’s an incredibly diverse, dedicated and bright group of people that sit around the REB table. I feel very fortunate to be amongst them and to have the opportunity to review cutting-edge research from some of the brightest minds pushing the boundaries of what is possible in medicine.

Dr. Sharon Yamashita (professional practice leader, pharmacy and REB scientific member, Sunnybrook)

Volunteering with the REB provides a unique opportunity to discuss and advance science. Like others on the committee, I enjoy learning about novel therapies and research questions, and being part of a collegial group of individuals who come together to discuss protocols, each with their own unique perspective and expertise. Our mission — to facilitate scientific advancement but at the same time, ensure the safety of our research volunteers — is incredibly important.

How has the COVID-19 pandemic changed the practices and processes of the REB?

Chris Cawston (REB community member)

COVID-19 presented us with some huge challenges, so beginning in March 2020, the REB chairs and research office led us through a dramatic transition, which included a switch to virtual board meetings. The volunteer members of the REB went above and beyond to review a massive number of new protocols related to COVID-19, including the formation of an emergency review team and processes that ensured we could rapidly facilitate important projects.

One of many examples included reviewing CATCO, a multi-centre trial in conjunction with the World Health Organization, that is investigating the safety and efficacy of different medications for COVID-19. Emergency meetings were held with little notice and board members had to work quickly to complete these reviews while always ensuring our usual high standards were maintained. In addition to the many protocols introduced to address issues raised by COVID-19, the team also managed to ensure the continued operation of approximately 2,000 active protocols — many requiring amendments to deal with logistical issues introduced by the pandemic.

My role with the REB makes me feel like, in my own small way, I helped contribute to our efforts to combat COVID-19 and cope with its effects.

The scientist’s perspective: What’s it like to work with the Sunnybrook REB?

Dr. Rob Fowler (senior scientist and critical care physician, Sunnybrook)

The REB at Sunnybrook is an active participant in research — helping to improve study protocols, making the research more accessible to patients and always being available for advice throughout the entire process.

They have reviewed over two dozen studies and trials that I’ve had the pleasure to help lead over the past 20 years. Over that entire period, the Sunnybrook REB has been just wonderful — they have deep expertise, are incredibly efficient and are always practical. When it matters most for patients and research teams, the Sunnybrook REB is there.

Interested in serving on the Sunnybrook research ethics board? Learn more.

The post Behind the research: Get to know the Sunnybrook research ethics board (REB) appeared first on Your Health Matters.

This year, a generous local company, D + H, has supported the program.

The D + H Summer Student Research Program started last week with an orientation session where Dr. Michael Julius, vice-president of research at Sunnybrook and SRI, welcomed students.

“It’s a great pleasure to have you here,” said Julius, to a packed audience in Sunnybrook’s Harrison Hall lecture theatre. “Some of the people you’re working with are the best on the planet. I would encourage you to interact with them and with each other.”

Read more about the program here.

The post Welcome summer research students! appeared first on Your Health Matters.