ALS RESEARCH: A PATIENTS PERSPECTIVE

A presentation by Sid Valo to the 3rd Annual ALS Canada Research Forum

It is indeed a privilege to have this opportunity to speak to you tonight about ALS Research from a patient’s perspective.  Let me first share with you my credentials as a person afflicted with ALS.

In June of 2004 upon returning from a brief vacation I was engaging in my regular workout when I noticed a significant reduction in the strength of my left arm.  I thought little of it, as I was recovering from an intestinal flu.  Later that month, I found myself cursing the fashion idiot who preferred button flys to that elegantly simple invention-the zipper.  For some reason, the fingers of my left hand struggled to manipulate the buttons on my fashionable fly.  I brought this to the attention of my family physician, who speculated that the source was likely a pinched nerve in my neck.  Not long thereafter, a debilitating attack of labrynthitis took me to my local hospital Emergency room.  Having ruled out a stroke, I was followed up by a neurologist to determine the source of the persistent weakness in my left hand.  A CT scan and MRI showed a potential calcification of, and impingement on my C5 vertebra.  My physical examination revealed significant upper body fasciculations which I acknowledged had been present for some time, however, now much more frequent and pronounced.  I showed no signs of upper motor neuron involvement.  It was my wife who to my astonishment, raised the spectre of ALS, which the neurologist initially felt was a very remote possibility.  I was referred to a neurosurgeon to address the potential nerve impingement involvement.  On physical examination and review of the radiographic findings, the surgeon flatly declared me not a candidate for a surgical A fix.

 

On November 2nd, 2004, I presented myself at the Sunnybrook Neuromuscular Clinic.  After a number of medical investigations, my diagnosis was one of MMN, Multifocal Motor Neuropathy, based principally on the results of a number of EMG studies and the absence of upper motor neuron signs.  I was treated with IVIG infusions over a period of three months with no apparent improvement.  Based on my unusual presentation and my physician’s concurrence, I sought further special MRI studies at the Mayo Clinic, expecting to have the MMN diagnosis confirmed.  On Friday, April 29, 2005, at 9:10 a.m., I was told that I had Amyotrophic Lateral Sclerosis, ALS.

 

I needn’t describe to you what followed except to say this is not a disease from which I alone suffer.  It is a devastating diagnosis borne by myself and every immediate family member.  I wish to emphasize that your work, your search for a therapy and a cure, will save not only the patient from the effects of this catastrophic illness but indeed it will serve to deliver an entire family from its crippling grasp.  We are a small patient community that is actually many times larger than anyone knows, if you include all of those who truly suffer the sequelae of the diagnosis. 

 

What then of the patient’s perspective? Handed a terminal sentence, what does the patient think?  On the most basic level; beyond “Why me?” it is certainly: “After 135 plus years, how can they not know?”. “When will they find out?”.  “Will it be soon enough?”. As a patient, I am gratified at the significant advances of the past decade but I hope tonight to bring you a more thoughtful perspective.

 

I consider myself fortunate.  My response to the inevitable question of “how are you” is: My infrastructure is crumbling, but my psyche remains strong, positive and in the moment.  Strong because of the exceptional wife and wonderful family and support system around me.  Positive because of my firm belief in the ability of science to achieve its goals, if not for me then for those that follow me.  And in the moment, because that is all I have, and I wish to use it as best I can.  For me, this is my “New Normal”.

 

What then, the more thoughtful perspective? Here again, let me establish my credentials.  I am a frustrated MD.  From the fifth grade on, all my scholastic activity was focused on science and medicine for I was intent on becoming a doctor.  That is, until first year university biology when they placed the cat in front of me on the dissection table.  My medical career came to an end.  My interest in science remained, and I collected a consolation prize, my Juris Doctor-not quite the same, but a doctor nonetheless.

 

When David and Denise asked me to speak tonight, the title of my presentation was already under active research.  Since diagnosis, I have relentlessly followed the progress of science in ALS research.  In November 2005, I attended the International  ALS/MND Conference in Dublin and I review weekly new abstracts in neuromuscular research.  More importantly, I have also directed my inquisitive mind to the question of how to accelerate the pace of research, who is doing what differently and with what result? I recognize a little knowledge is a dangerous thing, and that with it, I risk speaking out of turn, but my intent this evening is to provoke discussion and to share with this research community, particularly our up and coming researchers, my view of where, in the future, research has to go and funding will come from. 

 

In September of 2005, the mainstream media as represented by the Economist magazine noted a growing trend of A patient as researcher.  This role was borne of patients’ frustrations with the apparently slow pace of research.  It has resulted in a changing patient-researcher relationship as patients are becoming more proactive.  They are demanding more therapeutic options and faster results.  They are raising funds and establishing new and clearer expectations.  They are, in Coca-Cola parlance, choosing A New Research and rejecting A Research Classic. 

 

This is a trend that has been recognized by the Canadian Institutes of Health Research and the U.S. NIH, both of which have developed detailed and lengthy strategies to address the need for innovation in the research process and for the effective implementation of the new buzz word, A translational research, moving the basic research to the clinical setting. 

 

What then are the issues with A Research Classic?  Set aside funding for the moment. 

Few would argue that concerns exist about duplication of effort, lack of coordination among research centres, legacy academic issues such as Apublish or perish and the silos within which academia too often exist. The NIH has specifically recognized that the traditional divisions within health research in some instances may impede the pace of scientific discovery.  It has also pointed to the need to improve communication and access to data among research centres to avoid duplication of effort and increase the efficiency of research efforts.

 

Importantly, the spectre of competition, tacit as it may be, also impacts the progress of research at many levels.  Competition has its merits, but in the face of devastating illness, its disadvantages are rendered unacceptable.

 

Finally, the issue of intellectual property protection and its rampant spread versus open access would yield a topic for an entirely separate presentation. 

 

Who is driving the "New Research"?

 

At the broadest policy level, organizations such as the Milliken Institute’s Faster Cures Inc. and The Centre for Accelerating Medical Solutions are pressing the agenda of the “New Research” processes. These organizations are acting as catalysts, drawing together the funding agencies, the business community, the patient groups, and other critical stakeholders to develop new and innovative approaches to the management and funding of basic and translational research.  Additionally, the “New Research” is being driven by the funding organizations themselves and the new venture philanthropists who impose their own rigorous brand of thinking and decision making to not-for-profit foundations.  The "New Research" is proof of the old adage  “he who holds the gold makes the rules".

 

Let me give you some examples of the “New Research”.  Regrettably these examples all come from the United States. 

 

The Myelin Repair Foundation is a unique partnership between scientists and business executives which has removed the competitive nature of basic scientific research and substituted a collaborative strategic planning effort with measurable results.  This not-for-profit corporation, established by a successful entrepreneur, himself suffering from Multiple Sclerosis, has brought together five separate scientific teams, previously competitors, to work on a common research plan, share findings in real time, piggy back experiments to accelerate research, all as a means of finding new solutions in a faster, more cost-effective way. 

 

Project ALS, a NY based foundation established by an ALS patient and her sisters has raised 20 million dollars to fund directed research based on a team approach involving independent research groups working together and sharing results in real time.  They pursue research objectives established by a panel of advisors and draw upon specific scientific expertise regardless of its origin.  Their current project involves a collaborative effort among American, Canadian and UK scientists exploring motor neuron development utilizing stem cells. 

 

The Accelerated Cure Project is focused upon “developing a cure" rather then "finding a cure”.  The Project is doing this through the development of "The Cure Map". The Cure Map looks at the five possible causes of any known disease: genetics, toxic agents, pathogens, trauma, and nutrition. It identifies and outlines what existing research has already uncovered in each of those areas, and identifies what remains to be researched.

In support of the Cure Map, the Accelerated Cure Project is creating a large central  biorepository of tissue samples and clinical data from MS patients and matched controls throughout North America.  This tissue and data bank will be available to all contributors who agree to share their results, pursuant to a well defined protocol. It will provide researchers with the ability to explore the Cure Map and confirm or reject individual factors as a potential cause of MS.

 

Like the Accelerated Cure Project's Cure Map, the Pancreatic Cancer Action Network’s Cancermap is a resource that can promote broad-based strategies for research into a disease, improve coordination, and leverage resources across institutions. The Map seeks to connect the dots between all researchers involved in pancreatic cancer research to speed the development of national strategies and to leverage resources for pancreatic cancer research. In addition a Progress Review Group reviews progress and identifies issues, barriers, and needs across the continuum of pancreatic cancer research. The group delineates and prioritizes recommendations for research directions, related scientific questions, and resource and infrastructure needs.

 

Finally, let me share with you what I consider to be one of the most compelling examples of the “New Research” that I have come across.  Here again, it was the funding agencies who, contributing hundreds of millions of dollars to AIDS research, initiated a complete review of international research efforts to develop a therapy, in order to determine how effectively their funds were being used and, to develop a detailed strategy for the acceleration of this research. 

 

The Microbicide Development Project began with a “gap analysis”.  Teams of experts identified and agreed upon the crucial gaps and obstacles in: activity, leadership, physical infrastructure, human capital, coordination, networks, policies, funding, or other resources where limits hindered progress.  These teams then identified obstacles to action including specific logistical or knowledge deficiencies.  They then designated some of these as priority gaps and they produced recommended actions.  Finally, they identified unnecessary duplication of work and encouraged greater communication and coordination to eliminate it.  Having developed a strategic plan to go forward, progress is being monitored and guided by an international committee of experts in the field. 

 

So what is all of this telling us?  What is this "New Research”?

 

The “New Research” consists of team-based science drawn from across many disciplines and geographic centres.  It works on well defined problems with concrete attainable goals and clear action plans.  It uses collaborative tools such as structured communications and data banks.  It involves agreements on how research results, positive or negative, are reported and disseminated.  It requires openness to organizational change and to consolidation as a means to facilitate research progress and efficiency.  It is built upon trust and an agreed upon approach to intellectual property that maximizes collaboration in research. 

 

We set aside the question of funding at the beginning of this presentation.  Let me now address it briefly. In January of this year, the President of the Canadian Institutes of Health Research suggested that about one in five research projects would be funded when the current grants were announced.  Increasingly, the growth in research funding will come from philanthropic resources, more so than government.  I believe I have demonstrated the expectations that these funding agencies will have.  In future, those scientists best able to demonstrate their ability to operate within the “New Research” paradigm will prove most successful in obtaining funding. 

 

My comments to this point clearly have application to both basic and clinical research.  I wish however to draw particular attention to the current absence of significant clinical research in Canada.  I recognize that existing resources and funding have a role to play here too but let me share with you the patient’s perspective of this critical area of ALS research.  I am perhaps more fortunate than most ALS patients in that I have seized the opportunity to participate in American clinical trials.  This has necessitated some travel and commitment but it provides for me, the ALS patient, a crucial therapeutic benefit.  I am not sitting at home waiting for this insidious disease to take its inevitable course.  I am doing something to fight back.   Equally importantly, I am participating in the quest for a therapy or cure, not only for myself, but for all others, now and hereafter.   I cannot stress enough the undeniable and invaluable psychological benefit that participation in clinical research affords.  The Canadian ALS patient community is a uniquely homogeneous and accessible group for clinical study purposes.  Advantage should be taken of this natural resource.

 

An important first step would be the creation of a national tissue and data bank for use by all researchers. Here in Toronto Lorne Zinman, Janice Robertson, and Ekaterina Rogaaeva have begun to develop a tissue bank.  The February issue of ALS Research News contained a request by Dr. Guy Rouleau in Quebec for tissue samples in support of a study.  Consider how a central repository would facilitate and accelerate research.  What is needed is a common protocol and training for the collection and use of the tissue and data and for the sharing of research results. I urge the ALS clinician community and ALS Canada to seriously consider the establishment of such a resource as part of its overall research program. 

 

In conclusion, I strongly believe there exists in the Canadian ALS research community a unique opportunity.  The community is small enough to aspire to a cohesive and collaborative effort.  Its existence in Canada and its role internationally is well recognized. Drawing on this, I see an opportunity for you to establish a “New Research” paradigm in ALS. I would challenge you to undertake a “gap analysis” of the existing Canadian research environment and create an ALS Cure Map.  This would provide an invaluable model and impetus for the international ALS research community.  If replicated internationally, it would surely hold the prospect for a much accelerated and coordinated ALS research agenda.  I challenge you to lead the way.

 

I do not wish to overlook the crucial role our new up and coming researchers can and will play in the search for a cure.  I encourage you to question the status quo, challenge the norms and pioneer innovative ways to pursue the “New Research”. 

 

This then represents one patient’s perspective on ALS research. It is founded in those essential questions: Who, what, where, how, and why not, and the most important question of all, WHEN?

 

Thank you very much.