UCalgary Medicine Magazine Winter 2011

WINTER 2011

SUMMER 2010

A UNIVERSITY OF CALGARY Faculty of Medicine Publication

This way

to med school Calgary high school students get a peak at our Anatomy Lab… and possibly their futures

– p. 8

Bodies in motion

Using high tech toys to study movement disorders in children

– p. 6 Crossing over

Meeting the health care needs of our community is a top priority, regardless of medical speciality

– p. 10 Strength in numbers

Ganging up to fight chronic diseases

–medicine.ucalgary.ca p. 12

ucalgary medicine | Page 1

uCalgary

Medicine Vol 3 Issue 1 | Winter 2011

UCalgary Medicine is published three times a year by the University of Calgary Faculty of Medicine, providing news and information for and about our faculty, staff, alumni, students, friends and community.

For more information contact:

Managing Editor Kyle Glennie T 403.210.6577 E kglennie@ucalgary.ca

Dean Dr. Thomas E. Feasby

Vice Dean Dr. Ronald Bridges (interim)

Senior Associate Deans Dr. Richard Hawkes, Research Dr. Benedikt Hallgrímsson, Education Dr. Ronald Bridges, Clinical Affairs

Associate Deans Dr. Anthony Schryvers, Undergraduate Science Education Dr. Bruce Wright, Undergraduate Medical Education Dr. Jennifer Hatfield, Global Health & International Partnerships Dr. Doug L. Myhre, Distributed Learning & Rural Initiatives Dr. Joanne M. Todesco, Postgraduate Medical Education Dr. Frans A. van der Hoorn, Graduate Science Education Dr. Jocelyn Lockyer, Continuing Medical Education Dr. John Reynolds, Basic Research Dr. Michael Hill, Clinical Research Dr. Janet de Groot, Equity & Teacher-Learner Relations Dr. Kamala Patel, Faculty Development

Design and Production Kelly Budd, Radius Creative

Photography Carlos Amat, Dan Bannister, Trudie Lee, James May, Bruce Perrault

Free Copy/Alumni Update

To receive a free copy of UCalgary Medicine please call 403.220.2819 or email medcomm@ucalgary.ca The Faculty of Medicine is committed to staying in touch with our alumni. Please update your contact information at our website www.alumni.ucalgary.ca (click on “update your info”)

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PM AGREEMENT NO. 41095528 RETURN UNDELIVERABLE CANADIAN ADRESSES TO: University of Calgary Faculty of Medicine Communications & Fund Development Health Sciences Centre 3330 Hospital Drive NW Calgary, Alberta T2N 4N1

Winter 2011

WINTER 2011

contents

Volume 3 Issue 1 | winter 2011

pg4 Planting the seeds of science | Message from the Dean Preparing ourselves, and our community, for the future.

pg5 Breaking new ground | Philanthropy

Having spent the last 40 years building homes for Calgarians through his family owned business Shane Homes, Cal Wenzel has turned his attention to another important matter; our health.

pg6 Bodies in motion | Research

Studying motor disorders in children takes dedication, a multi-skilled team of researchers, and some high tech tools.

Cover Story

pg8 This way to med school | Service to Society

For many high school students, the path to becoming a doctor may seem like an impossible journey. But all journeys begin with that first step, something Dr. John Bertram is happy to help with.

pg10 Crossing over | education

For the Faculty of Medicine, meeting the health care needs of our community is a top priority, regardless of medical speciality.

pg12 Strength in numbers | research

26 researchers, 14 different disciplines, 6 research papers and 18 months. What does that add up to? One team of dedicated professionals tackling chronic diseases for the benefit of us all.

pg14 Light at the end of the tunnel | Service to Society

For over two decades, Faculty of Medicine members Dr. Torben Bech-Hansen and Dr. Bill Stell have been working to shed some light on congenital stationary night blindness.

On the cover A graduate student holds a human brain in the anatomy lab.

medicine.ucalgary.ca/magazine

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message from the dean

Planting the seeds of science Preparing for the future is a priority at the Faculty of Medicine. That may seem like a standard statement to make—everyone prepares for the future in some small way at the very least—but for us, this is a critical issue. Are we equipped to train the next generation of physicians, researchers and health professionals? Do we have the resources in place to continue to produce quality research as we do today? These are questions we continually ask ourselves and we can answer with a resounding ‘yes’. But what about our future students, what are we doing for them?

This question may seem obtuse, but it is one we have tackled as well. It’s one thing to recruit intelligent and talented students from around the world seeking to study medicine to come to our University, but what about the student who doesn’t know what they want to do? As I’m sure many can attest, often at such an age our futures seem clouded at best, even for students who excel in school. What if we could give those students a nudge towards medicine?

That’s precisely what Dr. John Bertram, a professor in the Department of Cell Biology & Anatomy, is doing. Six years ago Dr. Bertram started inviting high school students to the anatomy lab to learn about the human body. It’s here that students

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are given the opportunity to see cadavers and real human organs to help them understand how the human body works. Many of the students leave the sessions with an interest in science and medicine they never would have had before; others often have their inclinations towards medicine verified by the experience. Either way we are planning for the future of medicine, both for our school and our communities.

This is just one of several stories in this issue of UCalgary Medicine magazine that showcase our dedication to our communities and to our future.

We are helping children overcome motor diseases (page 6), we are expanding our training of post graduate students into areas outside of our typical scope to meet a need (page 10), and we are working together to fight chronic diseases and retinal disorders (pages 12 and 14). It’s because of the talented professionals mentioned in these pages that our future looks so promising, and I hope you enjoy reading about them.

Dr. Tom Feasby Dean Faculty of Medicine

Winter 2011

Philanthropy

Breaking new ground

By Lois Epp

Dr. Mark Swain and Cal Wenzel at the Faculty of Medicine.

For four decades Cal and Edith Wenzel ensured thousands of Calgarians had a roof over their heads through their family owned business Shane Homes. Now they’re looking after even more people with something just as important; their health.

In her early 20s, Carrie Paxson was diagnosed with a liver disease called autoimmune hepatitis. At that time the conventional course of treatment was to manage the illness as best as possible, anticipating that a transplant would likely be required one day—not an ideal situation given that up to 20% of patients will die while waiting for a suitable donor.

Fortunately for Carrie, hepatology, the study of the liver and its diseases, has made medical leaps and bounds in the last decade and a half. Across the nation, a close knit group of researchers and physicians are tackling these challenging issues, and Calgary is leading the pack.

Foundation Chair in Hepatology in the Snyder Institute of Infection, Immunity and Inflammation. Dr. Mark Swain, the inaugural appointee to the chair, cannot stress enough its significance.

“Over the past 20 years the field of hepatology has moved forward at an amazing pace, progressing from a side-branch of gastroenterology, into a field of study, research and therapeutics in its own right,” says Swain. “Much of this progress has been made possible by a better understanding of liver disease obtained through research.”

The timing couldn’t be better as incidences of liver diseases are on the rise.

Cal Wenzel is no stranger to breaking new ground. Over the past 40 years, Cal and Edith Wenzel, through their family owned business Shane Homes, have contributed significantly to the growth of Calgary, having built a great portion of the homes in Calgary.

Now, through their Cal Wenzel Family Foundation, the Wenzels are helping to develop another aspect of this community—that of health care through their support of health research.

“We believe it is important to give back to the community,” says Wenzel.

“There is no limit to the different areas, especially in health, that can benefit from more support so we’re giving a boost where we can.” With a total donation of $3.5 million, they directed their gift to support cardiovascular research, paediatric asthma research, and the lesser known area of hepatology research.

Thanks to their designated gift, the Faculty of Medicine is now the first in Canada to boast a dedicated chair in hepatology—the Cal Wenzel Family

medicine.ucalgary.ca/magazine

It has been estimated that up to one in 10 Albertans have some form of liver disease. Although stereotypically linked to alcohol or drugs, the truth is there are over 100 known forms of liver disease caused by a variety of factors, affecting everyone from infants to older adults. The main causes are viruses, toxins and metabolic derangements, and forms of liver disease caused by an overly active immune system which attacks the liver. Over 250 million people worldwide are infected with hepatitis B alone.

But progress is happening. “Through research, we can now currently cure many patients with hepatitis C and can effectively control, but not cure, hepatitis B infection in the majority of patients,” says Swain.

“I believe in the work that is done here,” says Carrie Paxson, now 40 years old. “I have benefited from alternative treatments available and I have witnessed new technologies that are not available elsewhere in Canada. I feel very fortunate to have access to the level of expertise that exists in Calgary.”

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RESEARCH

Bodies in

motion

Dr. Barbara Ramage works with a study participant in the Movement Assessment Centre at the Alberta Children’s Hospital in Calgary.

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Winter 2011

RESEARCH

Studying motor disorders in children takes dedication, a multi-skilled team of researchers, and as KYLE GLENNIE saw first hand, some high tech tools.

Take a stroll past a local playground on any given day and you’ll likely see plenty of kids hanging upside down on the monkey bars or climbing on anything that can support their weight.

Some kids are larger than others; some are faster than others; and some maybe seem less involved or not as enthusiastic about this part of their day.

Could it be that child isn’t interested in the playground? Perhaps.

Or could it be there are other factors at play?

“When a child is suffering from motor problems it can affect their social and emotional development, as well as their physical development. We’re interested in finding out if there are ways we can help improve the outcomes of these kids whether it’s at school or on the playground.”

The term motor disorder covers a variety of conditions that can affect children, and Dr. Deborah Dewey is interested in why these often occur together with such conditions as attention deficit hyperactivity disorder (ADHD), dyslexia and autism spectrum disorders.

“About 50% of kids who are diagnosed with ADHD also have a significant developmental motor disorder, and about 85% of kids with autism spectrum disorders also have motor problems,” explains Dewey. “It’s the same for dyslexia, of which about 3040% of kids have motor problems. We want to figure out why these often occur in tandem.”

The study, funded by the Canadian Institutes for Health Research, is called Developmental Motor Disorders: From Genes to Behaviour. Dewey is the principal investigator, but this is anything but a one woman research team. The study is multidisciplinary and is looking at the genetics, brain functioning, motor skills, language skills, memory skills, and executive function of children with developmental motor disorders and other neurodevelopmental disorders, and those without any motor impairments.

“Each child that we study completes a neuropsychological assessment, and from there many will go through further tests including neuro imaging and kinematic analysis,” says Dewey. So far, over 300 children have completed the neuropsychological

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assessments, and 120 have undergone functional magnetic resonance imaging (FMRI) and diffusion tensor imaging (DTI) of their brains, the most of any study on developmental motor disorders ever in the world. 90 of the children have completed a kinematic assessment of their movement.

“One of the tests we do is to have a child stand on a force plate that detects pressure, and we measure the movement of the child just while they are standing still,” explains Dr. Barbara Ramage, a co-investigator on the study. “We look at how close each child gets to the edge of their balance, and also how quickly it takes for them to get to the edge of their balance.”

Most children in the study aren’t in danger of falling while standing in one place, but the test isn’t used as a measure of balance. Rather it seeks to gauge how well a child can bring all their neural systems together to stand still.

“The goal of the research is to see if, for example, the brains of children who have developmental coordination disorder look similar to those of children with ADHD in terms of imaging, or if there is anything that would help us distinguish the two groups early in life,” says Dewey. “We also plan on looking at genetics and possibly doing some whole exome sequencing on the kids and their parents.”

Identifying how the brain of a child with a motor disorder works—and developing treatments for those who suffer from these conditions—is a long term priority for the study. But for researchers, it’s not a case of ‘locate and repair’ per se, it’s more like ‘locate and analyze’.

“What we may come to find is that some of these children are simply delayed from a motor perspective,” says Ramage. “Maybe an 11 year old with ADHD is similar to a typically developing seven year old, and with more training and if their brains are functioning normally we can just catch them up. Or perhaps there is a deficit there and they will never catch up. These are the questions we’re trying to answer.”

For the 300 plus children who have taken part in the study so far, it’s a question they’re happy to help find the answer to.

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Service to Society

This way

to med school

For many high school students, the path to becoming a doctor may seem like an impossible journey.

But as KYLE GLENNIE found out, sometimes all a student needs is someone…or something… to give them a little push.

How does a high school student begin his or her path to medical school?

When I was in high school I shied away from all forms of science; I’ll pass on biology thank you, and I physically could not stomach physics. I figured medical school was for students who took biology, chemistry and physics, and it was likely their parents were either doctors themselves or they forced their children into it. A cruel and shortsighted assumption, yes, but I will assume I’m not alone in this line of thinking.

“Our program really is great for the students because where they perhaps liked biology before, now they can see that medicine is what really interests them. And for some who thought medicine was their obvious career choice, perhaps after coming here they can see that maybe it’s not for them.”

The “program” that Dr. John Bertram speaks of provides high school students with an extraordinary opportunity: to view and learn how the human body works with cadavers and samples of real human organs.

“In each session I give the students a general introduction to the major organs and explain why the organs are in the positions that they are in the body,” explains Bertram, a professor in the Department of Cell Biology & Anatomy. “It gives them a chance to see anatomy up close and to show them more than just pictures in a book.”

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These are definitely more than pictures. Each student dons a white lab coat and a pair of rubber gloves and is able to see and touch the six cadavers on display. Also on hand is a preserved human brain the students are allowed to hold and examine, as well as prosections of other organs and body parts. This kind of literal hands-on learning is invaluable to students; maybe on this day more than ever.

“Some of our kids maybe haven’t had the opportunities that some other kids may have had, they aren’t exposed to this type of learning as much,” says Darren Whitbread. As vice principle of Forest Lawn High School, he knows that for some of his students this experience can be life changing.

The high school in southeast Calgary has gained somewhat of a reputation as a troubled school, fairly or unfairly. Regardless of the reputation, the school is delighted to be part of Bertram’s efforts to educate.

“I find some of our kids sell themselves short, but when they come here they think ‘maybe I can do this’. It sets them on a path that perhaps they wouldn’t have gone down in the first place,” says Whitbread. Bertram agrees, noting the Bachelor of Health Sciences program at the Faculty of Medicine has already had successful applicants come from Forest Lawn High School within the last six years when he started bringing students into the anatomy lab.

Winter 2011

Service to Society

Photos from left: Darren Whitbread, vice principal of Forest Lawn High School, and Kerry Offord, Grade 12 teacher, in the anatomy lab; Graduate student Andrea Smailys speaks to the students; Dr. John Bertram (far right) with high school student Nicholas Rollick (left) and Darren Whitbread; a student holds a human brain specimen; Dr. Bertram instructs the students; Grade 12 teacher Kerry Offord.

Not for the faint at heart

“Oh we’ve had people faint in here before, so we’re sure to let the students know that if they feel like fainting they should excuse themselves and step out of the lab, there’s no need to ask permission.”

It’s obvious Bertram is telling the truth when he calls this program one of the best parts of his job. He’s happy to allow me into the lab to view the session, and he’s fuelled by the student’s enthusiasm. This isn’t something he was forced to do, it’s something he set out to do six years ago as a way to support the educational community in Calgary. “We really are set up perfectly for this type of learning here, and it’s the same way we teach our medical students.”

And that’s exactly what he does. Around 12 high school classes come through the anatomy lab per year, mostly from teachers who have heard about his program and are interested in the unique opportunity for their students. While ensuring the students respecting the cadavers and the prosections on display was initially a concern for Bertram, those fears were quelled from day one.

“Almost all of the classes that come through here are the same in that they usually are shy at first and then you can’t drag them out of the lab once they get comfortable with everything. But what I’ve found is because we’re

medicine.ucalgary.ca/magazine

dealing with real material, the students take this very seriously and they are very respectful.”

For some students, the opportunity to too great to pass up. Even though Nicholas Rollick didn’t have any classes to attend, the Forest Lawn High School student still made sure he had a spot in the anatomy lab.“You don’t get the opportunity to see how the human body works in high school biology normally; we dissect animals but we definitely don’t get to see the human body,” says Rollick. “I’m really grateful to Dr. Bertram for this and getting some one-on-one instruction as well is great.”

I guess the path that leads high school students to medical school isn’t as straightforward as I thought.

Check out the video!

Watch the students learn in the anatomy lab at: www.youtube.com/ucalgarymedicine

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EDUCATION

Crossing

For the Faculty of Medicine, meeting the health care needs of our community is a top priority, regardless of medical speciality. At a small, unassuming clinic at the Foothills Hospital, MARTA CYPERLING got a first-hand look at what that actually means.

Dental resident Ricky Suri works on a patient at the clinic.

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Winter 2011

EDUCATION

Photos from left: Dental resident Devin Jones in the clinic; Resident Ricky Suri speaks to a patient’s family; Jones examines a patient.

over

It’s a unique program that helps fill a major need in southern Alberta and trains residents in a specialized field in need of more doctors. The clinic that houses it is much like any other clinic at the Foothills Hospital, and thousands of patients walk through its doorway every year. There is one major fundamental difference however, something that most people wouldn’t associate with the Foothills Hospital or the University of Calgary; this is dental clinic where dental residents are trained. And they’re part of the Faculty of Medicine.

The dental residency program, a partnership with both the University of Alberta Faculty of Medicine and Dentistry and Alberta Health Services, allows graduates from a recognized school of dentistry to complete an optional oneyear residency teaching advanced skills that could be used in a specialized practice. The program consists mostly of chair-side clinical teaching, as well as a series of lectures, journal clubs, rounds and seminars throughout the year. The residents work closely with doctors from UCalgary Faculty of Medicine to provide the best medical treatment option to patients without having to refer them out of hospital.

Based at the Foothills Medical Centre, the dental program allows the residents to work with medically compromised and special needs patients that they would never treat in a regular practice. “Patients are referred from hospitals, the Tom Baker Cancer Centre and the community,” says Dr. Antonietta Paladino, clinical director of the FMC Dental Clinic. “There is a wide range of patients with various medical issues.”

The clinic serves about 2,000 patients a year; some seek treatment prior to transplant surgery because their immune system is compromised and they are prone to infection and require special care. Other patients visit prior to cancer therapy, as radiation treatment can affect the jaw bone, and some patients require sedation or general anesthesia for dental work.

medicine.ucalgary.ca/magazine

The clinic serves the population of Calgary, southern Alberta, southwestern Saskatchewan and southeastern British Columbia, as it is the only hospital dentistry clinic in southern Alberta.

Devin Jones graduated from Dalhousie University’s dental program and is now part of the Calgary dental residency program. “It’s a really small program with only two residents and it allows you to work closely with specialists.

That’s one of the reasons why I was attracted to the program, it’s a lot of one to one time, several times a month.”

His colleague Ricky Suri, another dental resident, graduated from Boston University and shares the same sentiment, he likes the size of the program and he gets to help a very unique group of patients.

While the fee-for-service dental clinic has been around for years, the residency program was started in 2008. Two residents are currently enrolled in the program, a number that will hopefully expand. Both the residency program and the dental clinic are each accredited by the Commission on Dental Accreditation of Canada (CDAC).

Dr. Eduardo Kalaydjian, a clinical associate professor in the Department of Surgery and the man who started the program, says he’s received applications from a wide range of North American dental school graduates and from foreign graduates as far away as Australia. “The key to the program is the collaboration of medical and dental specialists as well as general practitioners within the program. The clinic is important as special needs patients are one of the most underserved patient populations in Alberta, and this program will ensure that the dental workforce will exist to meet the needs of these patients.”

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Research

Strength in numbers 26 team members spanning 14 different disciplines. Six research papers published in the last 18 months. The numbers are impressive for the Interdisciplinary Chronic Disease Collaboration, a coalition of researchers started right here in Calgary.

By Maria Turner

Stan Waterman has been a kidney patient for almost 45 years. Initially diagnosed with hypertension, Stan soon found out he had a congenital condition known as “horseshoe” kidney, in which the two organs are fused together. Today, Stan is living with 13% of normal kidney function, just shy of the limit for dialysis. He is all too aware of the complexities and challenges of living with a chronic illness.

In early 2009, Dr. Brenda Hemmelgarn, a kidney specialist at the Faculty of Medicine, together with fellow Alberta-based specialists Dr. Braden Manns and Dr. Marcello Tonelli, formed the Interdisciplinary Chronic Disease Collaboration (ICDC), a research team funded by Alberta Innovates–Health Solutions. The goal of the team is to directly improve the lives of patients like Waterman.

“Chronic disease in general has increased,” says Hemmelgarn. “Most recent estimates for Canada put diabetes at about 5% of the population, hypertension at about 20%, and kidney disease at 5-6% and up to 20% in the elderly population. These are very common chronic conditions.”

Current healthcare strategies to deal with chronic disease are limited. Often the patients who are at the highest risk of developing serious illness are not identified before their situation becomes critical. And the problem is worse for those in remote areas who may not have access to appropriate care. Hemmelgarn, Tonelli, and Manns decided they needed to do something different to improve the treatment of chronic illness in Alberta. So they invited healthcare policy and decision makers to work with the ICDC alongside researchers and clinicians. “By implicating decision makers at the early stage of research, we can make sure we are doing policy-relevant research which will have a real impact on patient care,” explains Hemmelgarn. The group now has 26 team members, including 11 from the University of Calgary, spanning 14 different disciplines.

This unique approach is already paying off. The group has published six papers in major international journals over the last 18 months, including a review paper in the Lancet, looking at early recognition and prevention of

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chronic kidney disease, and one in the New England Journal of Medicine on the use of phosphate binders in patients with kidney disease, emphasizing that an over the counter chewable calcium tablet (such as TUMS) was as effective as an expensive prescription medication when used to treat high phosphate levels in people with kidney disease. This is a very important result as cost effectiveness can have a great impact on access to treatment and patient compliance.

In addition, two papers published in the Journal of the American Medical Association focused on the best ways of identifying patients who were at high risk of developing kidney disease. The group discovered that adding a simple urine test to the standard blood test for kidney function better predicted those individuals at high risk of developing progressive kidney disease, myocardial infarction and death. They also found that a prompt added to a lab report form increased referral rates for high-risk patients.

Other projects are in the works. The ICDC is currently evaluating the impact of Alberta’s primary care networks on care and outcomes for patients with diabetes. As well, the group is working with Statistics Canada on a survey of patients with chronic disease to identify the barriers—medical, social, and economic—that these patients face in getting the help they need to manage their disease. Once the barriers have been identified, the group will look at different solutions to improve care. Results from the survey are expected in 2012.

Doing the research is only the first step. The ICDC also has a strong component focused on knowledge translation. “We need to get word out to the general practitioners,” says Hemmelgarn. “They see the bulk of these patients and they need information to help them identify those at the highest risk. That’s where we can have greatest impact.”

Stan Waterman knows just how important it is for patients to get timely medical care. He’s working with the ICDC as a patient volunteer. “I’ve had excellent healthcare,” he says. “If I can inspire anyone to get in the process early, by all means, that’s why I’m here.”

Winter 2011

Research

About the researcher...

Dr. Brenda Hemmelgarn is an associate professor in the Departments of Medicine and Community Health Sciences at the Faculty of Medicine. She is also a member of the Libin Cardiovascular Institute of Alberta and is supported by funding from Alberta Innovates-Health Solutions.

medicine.ucalgary.ca/magazine

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Service to Society

Light at the end of the tunnel For Faculty of Medicine members Dr. Torben Bech-Hansen and Dr. Bill Stell, fighting congenital stationary night blindness has been a long and arduous journey. But as COLLEN BIONDI found out, their dedication has shed light on some promising treatments.

When it comes to studying congenital stationary night blindness (CSNB), a series of retinal disorders, you want the best of the best—cutting-edge expertise in both ophthalmology and genetics.

Enter University of Calgary professors and close personal friends Dr. Torben Bech-Hansen, the Roy and Joan Allen Professor in Sight Research, and Dr. Bill Stell. These men, a world-renown geneticist working with the Human Genome Project and a retinal neurobiologist, are pooling their resources to examine the causes of this curious condition and to explore viable treatment possibilities.

“CSNB has a complex presentation where not everyone has the same constellation of features,” explains Bech-Hansen, a professor in the Departments of Medical Genetics and Sugery. What is constant is its presence in individuals from birth, though not always diagnosed until later in life because of the difference in severity among individuals, and the fact that it does not appear to be progressive.

What varies is its manifestation. A subset of patients have severe night blindness—needing to turn on lights in a dark room, having trouble navigating dim restaurants, dark parking lots or tunnels—while others are less affected in that regard; they normally have reduced visual acuity, can be moderately to severely short-sighted (myopic), or have unsteady eyes. Though some patients are legally blind, many can live with their low-vision experience, so the condition tends to be under-diagnosed.

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In the late 1980s, Dr. Bill Pearce, an ophthalmology colleague at the University of Alberta who was seeing patients with CSNB, contacted Bech-Hansen asking for help indentifying a genetic link to CSNB. Using classical gene-mapping techniques, Bech-Hansen’s laboratory discovered two previously unrecognized genes—CACNA1F and NYX— which code for proteins that are critical for allowing rod and cone photoreceptor cells to signal light-reception through the retina to the brain. A defect in this signaling process of the retina is assessed in patients using a tool called an electroretinogram (ERG); CSNB patients in general have an abnormal ERG. What the genetic studies found was significant changes in the DNA sequence of specific genes. “CSNB patients are mutant in genes that produce proteins that function in the formation and activity of photoreceptor synapses. The electrical circuits of the retina are blocked at the synaptic level,” says Bech-Hansen. This initial genetic research opened the door for DNA testing for CSNB, which is now successful in detecting the genetic basis of CSNB in some 80% of patients. Furthermore, efforts are under way to use so-called next generation high-capacity DNA sequencing to find the genetic causes in the remaining patients.

The next stage of the CSNB research was gaining an understanding of the biological consequences of these mutations. How exactly were these mutant genes blocking retinal function? Since it is impossible

Winter 2011

Service to Society

Dr. Bill Stell (left) and Dr. Torben Bech-Hansen are both members of the Hotchkiss Brain Institute at the Faculty of Medicine

to experiment at the cellular level with a patient’s retina, Bech-Hansen is working with the retina of another mammal—the mouse. Bech-Hansen and another long-time colleague, Dr. Derrick Rancourt, used genetic engineering techniques to create a family of mice having a mutant CACNA1F gene.

That is where Dr. Bill Stell, a professor in the Department of Cell Biology & Anatomy and the Department of Surgery, comes into play. He has been studying healthy retinal functioning for almost 40 years. “My history goes back to being a basic scientist without any clinical interest whatsoever,” he says. “After getting my PhD and then MD, I went with passion into the lab.”

And because of his work studying non-human retinas (those of goldfish, turtles, and chickens in particular), when Bech-Hansen came asking for help with animal research related to CSNB, it was a good fit. Stell was able to provide expertise in characterizing retinal circuitry, both structurally (using the microscope) and functionally (using a behavioural indicator called the optokinetc response, or OKR).

What they expected to find were misfiring or failing synapses, caused by genetic “spelling mistakes” that were thwarting healthy functioning— basically “a failure of communication in the retina,” says Stell.

But what they found was much more profound. There were no synapses at all, from rods and cones to other retinal cells. “This poses special challenges for therapies,” admits Stell, “because even at birth, a person affected by CSNB is already way past the time (in utero) when synapses

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should normally form. We don’t yet know whether we can turn back the developmental clock.”

The “CSNB model” mice are now undergoing a variety of trial therapies.

Bech-Hansen and Stell are injecting normal CACNA1F genes into mutant retinas to see whether restoration of normal gene function can re-initiate the formation of healthy synapses and improve vision. But since gene therapy is still somewhat futuristic and extremely costly, they will also test new drug therapies intended to mimic a healthy regulatory system and “read through” or ignore the mutation, allowing the systems required for vision to work freely. Finally, Stell and Bech-Hansen will look at ways to block another alarming response they have found to be caused by these mutant genes—cell death.

Clearly there is much work to be done. And although progressive research will ultimately mean improved vision for those suffering with CSNB, it may accomplish much more than that. “This work can apply to other genetic diseases that involve synapses in the brain or peripheral tissues,” explains Bech-Hansen. And, adds Stell, “if therapies for degenerative diseases in retina, brain, and spinal cord are to be successful, it is crucial to know what kinds of therapy are effective, and how long we can wait to apply them after degenerative changes have occurred.”

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The Inaugural Dr. Clarence Guenter Lecture on Global Heath

Learning &

Reflections of a Foreigner

Featuring Dr. Clarence Guenter 4:00pm, Monday, April 11, 2011 Theatre Three Wine & cheese reception to follow at 5:00pm HRIC atrium Please RSVP by April 4, 2011 to agamble@ucalgary.ca, or 220-7073 Limited seating PM AGREEMENT NO. 41095528 RETURN UNDELIVERABLE CANADIAN ADRESSES TO: University of Calgary Faculty of Medicine Communications & Fund Development Health Sciences Centre 3330 Hospital Drive NW Calgary, Alberta T2N 4N1