Alzheimer’s Society of Ontario – All President’s Meeting

April 13, 2007

Good morning members, administrators, guests and especially volunteers of the Alzheimer’s Society of Ontario.

Let me begin by saying how honoured I am to be able to address such a caring and dedicated group of individuals, working together to improve the lives of Alzheimer’s sufferers today, and towards the final goal of tomorrow which, I would argue, is not so far away as we previously feared.

Support services and information resources like the Alzheimer’s Society of Ontario are now well-established with clear mandates, providing immediate relief to the suffering of those affected by Alzheimer’s and their families.

Also, research centres around the world, and the CRND right here at home have been making tremendous advances in understanding this disease, and beginning to make progress towards slowing it, and eventually reversing it. I will look closer at the successes of the CRND in more depth in a few minutes.

Today I would like to talk about the distinct differences between illness and disease – hammered into my head as a medical student – and why it has served the Alzheimer’s Society of Ontario to see Alzheimer’s as both an illness, profoundly affecting the life of a single individual, and a disease with a discoverable cure.

Modern pathology can be traced to Rudolf Virchow, a 19th century German clinician and academic who was a key champion of modern medicine and stressed the importance of “thinking microscopically.”

Virchow had many discoveries to his name, including leukaemia and the theory of Omnis cellula e cellula, or “every cell originates from another existing cell like it.” This theory contributed to his further theories of disease, for he could now recognize that not a whole organism, but only certain cells within that organism, should be regarded as “sick,” even though the associated symptoms might affect the entire body.

Virchow’s observation has held true through generations of pathologists, and serves as a powerful analogy for disease in society; although a disease may only directly cause one individual to be sick, it affects a much wider group of people than that one person: those friends, family members and coworkers who don’t feel the primary symptoms of the disease, but are nevertheless profoundly affected as it runs its course in the sufferer.

Furthermore, Virchow strongly advocated for social and political reform, stating that physicians should act as “attorneys for the poor,” and that outbreaks could not always be solved solely by treating individual patients with drugs, but only through radical action to promote health within an entire population – to treat disease as a social problem as much as a biological one.

Alzheimer’s disease is – unfortunately and heart-breakingingly – one of the most social of diseases facing us today.

Of course the biological aspects cannot be denied:

• The buildup of abnormally folded amyloid beta protein in the brains of Alzheimer’s patients
• An accumulation of amyloid plaques and neurofibrillary tangles
• The gross diffuse atrophy of the brain and loss of neurons, neuronal processes and synapses in the cerebral cortex and certain subcortical regions; and
• The personality changes and memory loss that can, in the worst and most neglected cases, result in death.

But the social aspects of Alzheimer’s and the personal toll it has on those not suffering directly from the disease have put this disease in a category of its own.

The change in personality and withdrawal of sufferers from the social aspects of their life are perhaps the most wrenching consequences, which many of us here – myself included – have seen first-hand in loved ones.

Most physical ailments rob us of the functions that enable us to actively participate as family members, workers or active members of the community, but leave intact the mental and emotional functions so necessary to our humanity.

In many cases the body may be wracked, but the mind goes on, allowing the individual – especially with today’s technological assistances – to still have a fulfilling and complete life. Just look at Stephen Hawking, for example, a man who has accomplished so much in spite of his physical debilities, and soon – with assistance – will even overcome these physical limitations to take a trip into orbit.

Ailments like Lou Gehrig’s disease or cancer – as terrible as they are – at least permit us to have a sense of completion and farewells before they take their final toll.

These are in contrast to Alzheimer’s, which leaves intact the physical person, but destroys the soul of the individual, taking loved ones from us even as it leaves their physical presence behind.

As a result, the burden is placed on family members and caregivers, fortunately guided and assisted by organizations like this the ASO.

All of us in this room have seen the patient in the early stages, the loss of control and fear of depersonalization and dependency. Thus it is with Alzheimer’s that we face a multi-faceted challenge to find the path of disease and prevention eventually, but also shorter-term treatments to ameliorate the course of the disease, and one day that we might prevent and assist the sufferers of tomorrow.

Today, however, it remains necessary to support patients and family members of current sufferers, those already afflicted with Alzheimer’s, who – with great sadness – realize that any cure will probably come too late for them.

This is perhaps the most valuable role of the Alzheimer’s Society of Ontario; to provide care, education and act as an agile resource for sufferers and their family, while you still steadfastly raise funds for a cure.

This fundraising is of vital importance to the CNRD and your national peer review research program, and I have agreed to have my name associated with your current campaign, the goal of which is to raise $8.5 million for research and services.

I would now like to make that distinction between disease and illness, as I know first-hand how important it is for medical students to see not diseases, but only illnesses born by individual patients; the lived experience that we must be concerned with …

And it is important to engage not just medical students, but the greater community as a whole for the need to focus not just on science-based medicine, but also narrative-based medicine. That ultimately the symptoms of an ailment are born by a family. This is especially true in the case of Alzheimer’s disease; a situation that the Centre for Research in Neurodegenerative Diseases at UofT has long recognized …

Prior to my speech this morning, I asked Peter St.George-Hyslop to provide me with a brief update of the work of the CRND, from which I might shamelessly steal in order to pass on their great news to this audience. Thankfully, he’s as generous with his clinical admirers and plagiarists as he is in his professional life … the next few paragraphs draw heavily upon his contributions.

The team at the CRND has worked on the molecular genetics, molecular biology and cell biology, animal modelling, and on the design of potential therapies for several neurodegenerative diseases including, most notably, Alzheimer Disease.

The CRND has cloned at least five different genes associated with risk for Alzheimer’s, including the presenilins, and most recently, SORL1 as a common gene for late onset forms of Alzheimer’s.

They have been major contributors to consensus decisions about the ethical and legal use of gene-based tests for diagnosis ad prediction of risk for incurable, heritable diseases of the brain. More concretely, they have then used these genes to work out some of the early events in the pathogenesis of Alzheimer’s, showing that the common, unifying feature of all of the known genes causing it is the accumulation of the amyloid beta-peptide, a proteolytic derivative of the amyloid precursor protein (APP). In so doing, they have discovered a novel form of proteolysis (presenilin-dependent regulated intramembranous proteolysis) in which membrane proteins are cleaved (by the presenilin proteins) in their hydrophobic transmembrane domains.

This hitherto unknown form of proteolysis plays a key role not only in the genesis of the amyloid beta-peptide in Alzheimer’s, but also in several fundamental physiological signaling events such as Notch signaling during embryonic development. They have also used the genes causing Alzheimer’s to create realistic models on this disease in cultured cell systems and in transgenic rodent animal models.

Finally, the researchers at CRND have exploited their knowledge of an A-Beta-induced biochemical cascade leading to neuronal death in Alzheimer’s, to explore potential therapies. They have shown that antibodies to A-Beta which can be induced by vaccination with A-Beta, improve the brain pathology and the cognitive function of the transgenic mouse models of Alzheimer’s.

A therapeutic trial using the full length A-Beta peptide as a vaccine was started, but had to be stopped due to a low frequency of autoimmune side effects. The CRND team then dissected out which epitopes of A-Beta led to a therapeutic effect (residues 1-11), and which epitopes led to the auto-immune side effects (residues 20-42). This is now the basis of several new therapeutic trials of passive immunization.

Subsequently, the CRND has developed a small, drug-like molecule (scyllo-inositol) which inhibits the aggregation of the relatively inert A-Beta monomers into highly neurotoxic oligomeric assemblies.

In July 2006 they have shown that, when administered orally to the transgenic mouse models of Alzheimer’s, scyllo-inositol effectively reduces the brain levels of oligomeric A-Beta. As they predicted, the reduction in the brain levels of oligomeric A-Beta in turn both prevents (if given pre-symptomatically) and reverses (if given many weeks after the onset of disease) the cognitive impairment, synaptic damage, Alzheimer-like neuropathology, and the accelerated mortality of the mice.

Scyllo-inositol is currently in Phase 1 human clinical trials being conducted by an Ontario-based pharmaceutical company (Transition Therapeutics). Phase 2 trials are expected to begin in the summer of 2007.

The CRND is making powerful advances in investigating and arresting the physical aspects of the disease, while the Alzheimer’s Society of Ontario continues its work to raise funds and to lessen the impact of the social side of the disease.

Speaking on behalf of one large, and so far successful model for an institution of scientific research and discovery, I would like to say that the University of Toronto is grateful and appreciative for your work – and the work of our local chapter specifically, which I have a previous personal relationship with.

Your leadership provides us with a strong example of how this disease can be beaten back.

It is exceptionally difficult for families of sufferers to know that there is no immediate cure, but a tremendous relief to them to discover that your organization does offer immediate support …

I understand that the theme of your meeting this year is New Directions in Philanthropy; and that you’ll be looking at new ways to develop capacity support to raise funds for services at the local level while also raising funds collectively to support the CRND and to meet your commitments to the national peer review research program.

Between the local chapters and your provincial office, I understand that you have an ongoing pledge to the CRND of $2.5 million over five years, and that this is your final year of that commitment.

I also recognize that it can be difficult for some of your smaller chapters to raise these funds, especially when it can be seen as sending money out of their community to the heartless financial centre that is Toronto.

First, I would like to convey that we face a somewhat similar problem at the University of Toronto in seeking funds from philanthropists or alumni, who might now be living abroad or across the country and no longer have a close connection to UofT – and I know that it can be difficult.

And to your chapters across the province, I would like to stress the importance of your work, and encourage you to see it as a collaboration with Toronto; that I hope you share the news of the accomplishments and advancements of the CRND I outlined earlier, which could not have been possible without the support of chapters from across the province.

The family that is the Alzheimer Society of Ontario collectively contributes to the province-wide fundraising that support the remarkable successes of a research centre … that just happens to be located in Toronto.

Secondly, speaking from my own experience, the University of Toronto similarly has long experience with organizing fundraising and campaign drives, or “campaigns of campaigns,” working within our own institution to make sure we’re not tripping over each other in seeking support;

Which is why I know the work of the ASO can sometimes be so difficult, as you face similar challenges in seeking support against other organizations and diseases and causes, some of which may seem more immediate or acute.

I know you are juggling a dual mandate, and doing it professionally and exceptionally well within Ontario, allowing our researchers to make their own advances and contribute to the world’s databank of knowledge about this disease.

In this context, it is important to recognize the need for balance – your chapter leadership across the province will always be faced with the difficulty of providing support to your immediate community while continuing to invest in research during this time of such great promise.

I know you understand this delicate balance, and I also know that your leadership is up to the task, as it has shown itself to be so competently to date.

Your current campaign is well underway, and I understand that a number of chapters have elected to increase their funding to research this year.

I would also like to make a particular acknowledgement to the Alzheimer Society of London and Middlesex, who championed the start of this campaign with a $1 million pledge …

In closing, we – and now I am once again speaking as a member of society who has been personally touched by the effects of Alzheimer’s – are grateful to you because we know your job is tough.

We also know that your job is probably going to get harder before it gets better, given the potential of Alzheimer’s to increase as the population ages.

But I want to thank you, for your compassion, dedication and leadership, and I would like you to know that as a society, we are making very real progress in intervening, slowing and even reversing this disease.

I do believe that definite treatments are almost within our grasp, and that we may yet see them within our own lifetimes.

To return one last time to Rudolf Virchow, I believe he would applaud your advocacy in the social aspects of this disease, while giving important regard for the physical aspects. I think he would agree that the Alzheimer’s Society of Ontario is an ideal model for a modern, successful, caring and holistic organization, especially combating a disease like Alzheimer’s.

Your successes inspire us all. Thank you for the privilege to be able to address you today. I will now take a few minutes to answer questions …

Check against delivery.