Exciting New Research

Author: Meg Macdonald, ALS/MND Patient Fellow

(all photos by Jennifer Chase)

I was chosen as a patient fellow for the ALS/MND International Symposium in Boston in early December. I was looking forward to learning a lot and meeting researchers and the other patient fellows.

The day before we were going to fly across the country to Boston, my husband, Stan, was hospitalized with life threatening septic shock. This forced me to cancel my trip to the conference.

But through social media and the ALS/MND International Symposium phone app, I got a message from a woman named Jennifer Chase, who has the C9ORF72 gene mutation like me. Jennifer lost her mom (who had FTD then ALS) and sister to ALS and her sister was one one of the first commercially tested patients confirmed to have the C9ORF72 gene. Jennifer is a brave sister in that she decided to get tested herself. She does have the gene mutation and has been learning all she could since finding out and she has been participating in research studies. She was attending the meeting on her own and she agreed to send me photos and updates. I appreciate her so much because she allowed me to learn through her eyes. What follows is a summary of the updates she sent me.

the registration table

There was a display of ALS/MND patients from all represented countries, including the awesome Osiel Mendoza from the USA.

Jennifer also sent me a photo of the registration swag.

The swag included the Nature Outlook from which I quoted two weeks ago

And now her report on the first day:

The Opening keynote speaker, Dr. Jeffery Rosenfeld from Loma Linda University, spoke about the need for a new paradigm: the need to define and stratify as done in MS, epilepsy, and headache. Even if lines are drawn wrong at first it’s time to start. He also said that biomarkers are what need to be tracked in clinical trials. The patient’s functional rating scale (FRS) doesn’t give results quickly enough.

Then there were awards:

  • Humanitarian award to the guys that started the ice bucket challenge – Anthony Senerchia, Jr. (awarded posthumously), Patrick Quinn, and Pete Frates. Pete’s mom Nancy accepted the award.
  • Forbes Norris Award to Dr. Merit Cudkowicz of Massachusetts General Hospital (and Jennifer’s neurologist) for her passion in researching and caring for patients with ALS and finding the cure.
  • The Paulo Gontijo Research Award to Marta Van Blitterswijk, MD, Ph.D of the Mayo Clinic in Florida for her work attempting to understand the variability among patients with ALS, including age at which it starts, presence of dementia, diesease progression and survival. Most of her patient centered work has focused on the C9ORF72 mutation.

Then Jennifer sent me this photo of ALS TDI researchers. The two on the right are working on C9ORF72 research

She said the rest of the morning was good, although nothing specific to C9 was covered. The Symposium registration was the highest ever – 1281. The scientific sessions were packed. She even saw people on chairs outside the rooms. She said she thought there were slightly more people with ALS there than 2 years ago.

The first afternoon session had a lot about the nuclear pore membrane and C9ORF72. One of the sessions was about SRSF1 (a protein coding gene and nuclear export adaptor) and C9 as a potential way to block the deleterious C9 while allowing the good C9 to work. They are looking at three potential approaches in fruit flies.

She walked through the posters not during the poster session, because of being too tired – I know I would have been exhausted . She noted one that described ALS as the nice person’s disease, and the poster said it looks like some truth to that because the characteristics that make people with ALS nice may be associated with risk factors in lifestyle and occupation.

She went to the clinical trials session on Friday afternoon.

  • Mastinab – normal progressors with less than a 1.1 decline on their FSR showed a slowing of decline at highest dose. There are reports of study irregularities though.
  • Tirasemtiv failed but a related drug is still in trial.
  • Ibudilast – Jennifer said it was confusing. She said they are hoping it slows FSR decline but it needs more study.

Moving on to the Saturday morning session, there was a hopeful presentation on a mechanism to help drugs bypass the blood brain barrier.

She said the biggest deal was Frank Bennett who is Vice President of Research for Ionis, in Carlsbad, CA, which is one of two companies developing the antisense drug. It is already being tested on ALS patients with the first gene defect identified – SOD1 and Bennett said the trial is going well. He also showed a video of kids with Spinal Muscle Atrophy who have been treated and the results were amazing – they were able to meet developmental milestones that untreated patients never could.

Another takeaway was from a presentation from Dr. Michael Benatar of the University of Miami who has been doing pre-familial ALS research – there may be a biomarker sometime that can detect disease before it is obvious clinically which would be a window for treatment for carriers. That would be very exciting.

C9 ALS normally has an average progression rate, but there are subsets – one where there is little progression for years (10 or more years) and another subset where progression is brutally fast. The doctor who was doing extensive genotyping discovered that these brutally fast progressors have a “rare deleterious variant” of the C9 mutation – they all died within a year.

Jennifer also went to Dr. Nick Maragakis’ presentation on excersise. She said basically supervised exercise (stretching, resistance, or cardio) did not hurt the study group but it not help ALS either. But I know from experience that exercise can help quality of life.

Then on to Sunday, the last day. She said there was lots on basic C9 research. Dr. Marka Van Blitterswelk (who won the research award) spoke about her findings on post mortem studies of C9 FTD with and without ALS. It was all good science and increased understanding. This work could not have been completed without the brave C9 patients who donated their brains, and their brave families.

Dr. Nazem Atassi presented on a PET MRI study which is not C9 specific but he thinks it can be used for smaller, faster phase 1 and 2 trials because it has a strong signal.

Dr. Brown giving the closing remarks

The closing session speaker was Dr. Robert Brown, of UMass Memorial Medical Center in Worcester, MA, who has been studying ALS with a special interest in genetics for a long time. He said the C9 antisense trial will be coming up in late 2018 (although I have since heard it may be sooner, and I hope to participate).

I had two comments from family caregivers from my blog requests before the conference.

The first one is from the sister of an ALS patient in California. He was diagnosed in March with familial ALS. After finally getting approved for Radicava he changed his mind so he could apply for the Nurown Phase 3 stem cell trial, and one of the requirements was to not be taking Radicava in the 30 last days. His breathing is also declining quickly and he won’t qualify for the trial if his breathing is below 60 percent Forced Vital Capacity. His sister would like to see changes in trial criteria. Why should a patient have to give up a promising treatment to participate in research? Of course trials are controlled scientific studies but it can lead to very frustrated patients and families.

I too have had frustrations with clinical trials. Many of them exclude patients with feeding tubes. That makes me think that the drug being tested might not be available to patients with feeding tubes.

Cathy Collet, a patient fellow committee member, reported that neurologists are skeptical about Radicava’s efficacy because of the small clinical trial, but glad to have it in their tool bag. I am taking a break from Radicava treatment to sort out unwanted side effects or whatever is causing my sinus problem.

The next comment was from the daughter of an elderly ALS patient in Canada. She is frustrated by the lack of studies on geriatric patients, and the tools to explain feeding tubes and suction to an 88-year-old. She also has observed that weight loss and slurred speech in the elderly is usually attributed to stroke. Cathy Collet said there was no mention of diagnosis in the elderly, and that is near and dear to her heart because her mother was diagnosed in her 70’s. It is an issue that sorely needs to be addressed.

I am sorry that I was not able to attend but I am so appreciative of Jennifer and Cathy for sharing information.

(Meg published this blog post on her own blog as well at alteringlifespectations.com)

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‘Just remember you have every right to be here’

Author: Andrea Peet, Person with ALS, ALS/MND Patient Fellow

Before the Symposium and throughout it, I kept getting the same curious advice from basically everyone I knew who had attended the conference in years past: “Just remember that you have every right to be here.” While some put a more positive spin on it (“It’s so nice to actually see patients here this year”), I came away feeling like I was a high school student getting to sit in on a parent-teacher conference.

As in, ‘we are talking about your progress but not in a way you would understand. We’d prefer to let the experts talk and fill you in later on how things are going. But since you’re here, please refrain from asking silly questions or pushing back on how the classroom is being run.’

But here’s the thing: we students (patients) see things you don’t, and we most certainly talk amongst ourselves. We too want to succeed (aka live), so I’d argue that a few well-placed, “mature” students (patients) could make the job – keeping us alive better and longer – easier. At the very least, we might even teach you something.

Take Session 2B (Autonomy and Quality of Life) on having hard conversations with patients, like making the diagnosis of ALS, talking through difficult choices on breathing assistance, or end of life issues. I appreciated Dr. James Tulsky’s “evidence-based approach” with research demonstrating how critical it is for doctors to be able to communicate effectively with their patients. But how much more impactful would the session have been if a person with ALS had said clearly to the audience that yes, we want straight answers, compassionately delivered? I guarantee it would have driven Dr. Tulsky’s point home beyond the statistics. Maybe that memory – plus the data – would give neurologists more confidence to launch into those tough conversations, and we patients wouldn’t have to wait as long to be diagnosed. Or maybe their empathy would empower us to make decisions earlier, before they have to step in and force one when the situation has become desperate.

In that same session, Dorothée Lulé from Germany presented findings from her study, which concluded that locked-in patients actually feel like they have a decent quality of life. I think everyone in the packed ballroom was moved by Stephen Finger, Ph.D. (a fellow fellow) commenting after that many people with ALS in the US would like to continue living, but struggle with burdening family members to care for them or facing the enormous expense of paying for around the clock assistance (read more of his eloquent argument here). It’s an unbelievably valuable message that probably would not have been raised without patients at the Symposium.

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“Oh never-mind, he hadn’t brought out the wig yet 😂 NOW we’ve reached the new level.”

One final example: the Right to Try panel discussion. I spent much of that session wishing – wishing there was a patient advocate on the panel (I heard later that there was supposed to be one), wishing other ALS patients were in the audience to listen to the counterarguments, wishing that the Right to Try campaign had been more of a collaborative effort. What if – before all the online petitions, bills drafted, and congressional hearings – patients, doctors, researchers, and drug companies had all come together to discuss the limitations of the FDA’s Expanded Access Program, the doctors’ concerns, the risks to the clinical trial process, and incentives to draw industry in? How much stronger would the movement be if there was both demand AND supply?

But where could such a discussion start? Well, the ALS/MND Symposium…but only if patients were in attendance. Otherwise, it’s just experts talking to themselves.

I expect there’s a concern that encouraging people with ALS to attend the Symposium means watering down the material. My suggestion: don’t. There are several patient-centric conferences out there already, but what about patients who want to go deeper into the science? Or, say, run a nonprofit like mine that raises money exclusively for cutting-edge research? Just make it clear in the marketing (a couple of session titles would probably do it).

In his opening keynote address, Dr. Jeffrey Rosenfeld called for a dramatic paradigm shift in how researchers define and study ALS/MND. I would submit that it’s also time to change how the MNDA views patient participation in the Symposium – as partners, as resources, as experts of a different sort.

After all, we are the only ones in the world who think about this disease more than you do.

 

Cannabis Looks Promising for Improved Quality of Life

Author: Sue Pondrom, ALS/MND Patient Fellow

I’ve heard anecdotal accounts and references to actual research studies that support the use of cannabis (marijuana) for relief of amyotrophic lateral sclerosis (ALS) symptoms such as pain, muscle spasms, even insomnia.  I am most interested in the use of cannabis to reduce anxiety, stress and decrease depression.  I was diagnosed with Bulbar-onset ALS in March 2017 and try as I might, I can’t put a positive, forward looking face on my disease.

That’s why I wanted to attend a portion of the 15th Annual Allied Professionals Forum December 7, 2917 in Boston, Massachusetts. It was titled “Cannabis and its Usage in Symptom Management of ALS/MND.,” I was already in town for the 28th international Symposium on ALS/MND, which started the next day.  My participation in the symposium was thanks to a group of non-profit organization staff, researchers, academicians  and philanthropic individuals who funded attendance for a limited number of patients.  Their goal was to bring patients together with researchers to ask questions and share information, and increase the dissemination of ALS research information in a patient’s “voice”.  We patient fellows chose to attend sessions that interested us.

Speaker Leslie Ryan of the Rocky Mountain Chapter of the ALS Association, represented associations throughout the US who had participated in a 2017 survey of why and how patients were using cannabis.

Among the survey findings:

65% of the 500 responses from throughout the US said they were not using cannabis; 5% had used it, but stopped; and 30% were current users. The majority of non-users either didn’t use by personal choice or because it was illegal where they lived. For 17%, it had never been offered as an option.

93% of respondents whom reported using cannabis said they believed cannabis had been effective in managing their symptoms, which included pain, cramping, muscle spasms, anxiety, insomnia and weight loss.  Patients reported various means of administration (smoking, edibles, oils, creams) but for the most part, didn’t know what type of cannabis they were receiving, i.e. CBD (medical cannabis) or THC, the “high” variety.

Regarding support of the health care team:

  • 44% of patients have not discussed cannabis with their health care team
  • 43% believed the team was supportive but had not yet prescribed cannabis
  • 9% said their doctors prescribed the drug
  • 4% were told by their doctors not to use it.

And then there was the part of the survey that particularly interested me.

91% of those using cannabis said it improved their quality of life by decreasing anxiety, stress, drooling and depression.  They had more energy to complete tasks, less fatigue, they slept better and had decreased insomnia. Patients even experienced increased intimacy and sex drive.  60% said cannabis helped them cope with ALS and its progression.  Ms Ryan said these findings were as important to them as the physical results.

It was more than enough for me.  My neurologist has said he would prescribe cannabis and it’s my first request when I see him at the next ALS Clinic.

NOTE: A recording of Ms Ryan’s presentation is made available by the conference organizers online here.

What to Do With Joe: Observations on Patient Interaction and Pre-Approval Access

Author: David Peet, husband and caregiver to ALS/MND Patient Fellow Andrea Peet

In reflecting on my experience at the 28th annual International Symposium on ALS/MND, I did not immediately find myself thinking about treatment updates and research news.  Instead, my focus shifted to a rather unusual place: a fictional teenager facing jail time.

Let me explain.

When observing a panel of presentations focusing on pre-approval access to unapproved medications. The panel included comments from Alison Bateman-House, PhD, MPA (New York University), Jess Rabourn (WideTrial) and Richard Bedlack, MD (Duke University).  I couldn’t help but think of my “Legal Ethics” course in law school and the competing theoretical models for how lawyers should interact with their clients with respect to legal decision-making.

Upon returning home from Boston, I dug out my old textbook and found the following hypothetical about a similar life-or-death situation (paraphrased):[1]

  • You are an experienced attorney who has a long career litigating juvenile court matters. One day, Joe, a fourteen-year-old boy, and his parents come to see you.  Joe has been charged in juvenile court with robbery and assault.  Joe says he can’t remember anything other than being at the scene of the crime with two of his friends.  You agree to take Joe’s case and Joe’s parents agree to pay your fees. 
  • During your initial investigation, you learn that Joe has no criminal record but that he does have a history of severe learning difficulties and psychological abnormalities. An independent psychological evaluation indicates that Joe is in need of significant psychiatric counseling to avoid more serious problems.  Despite your attempts to contest the merits of the charges, Joe is found guilty in juvenile court and the district attorney now wants to place him in a detention facility that has little in the way of psychiatric counseling.  Based on your experience, you believe that with the help of a doctor and a sympathetic probation officer, you could still persuade the judge to grant probation with placement at home and therapy under a doctor’s direction. 
  • You discuss the options with Joe and he expresses a clear preference against psychiatric treatment. Based on your experience, you think that placement in the juvenile detention facility would be a decision he ends up regretting.  How do you advise Joe?

This hypothetical establishes the groundwork for a very difficult decision for Joe’s attorney, who finds herself stuck between her presumed understanding of Joe’s best interests and Joe’s stated preference.  Would lawyers taking a more paternalistic view of their role truly serve their client if they pursued a path leading him to psychiatric evaluation?  Alternatively, would lawyers who execute Joe’s plan to go to juvenile detention “diminish the legitimacy of the legal system and profession” by “abdicating responsibility for the consequences of their actions”?[2]

I would be interested in hearing clinicians’ views on how to act on Joe’s behalf.  I’d guess that most of them would quickly conclude that Joe is simply too young, too uninformed on the ways of the world, and too ignorant of the potential consequences of his decisions to have full autonomy in pursuing a particular outcome.  But at what point does caring for patients become thinking for patients?

Indeed, the parallels between the predicaments that Joe’s lawyer and ALS clinicians face are as plain as day.  At the Symposium, clinicians expressed the diverging perspectives on how to resolve concerns over the legal, ethical, and moral consequences of their actions.  For some clinicians at the Symposium, pre-approval access seems like a slippery slope that likens a doctor’s role to that of a pharmacists—a distributor medication incapable of exercising judgment as to the medical necessity of such treatment.  For other clinicians, knowledge pre-approval access is a necessary component of truly treating a patient, and clinicians who ignore avenues for access are guilty of not only some measure of professional negligence but also of failing to truly listen to their patients’ desires.

The tension for ALS clinicians is also magnified as a result of increased patient sophistication and other “gatekeepers” that don’t exist between Joe and his attorney.  First, methods for patients and caregivers across the world to obtain, share, and digest information about new and diverse potential treatment options are increasingly user-friendly and ubiquitous.  The collective sophistication of patients and caregivers is higher now than it has been at any point in the history of the disease.  The patients of today are well-informed, and, by extension, the knowledge gap between patients and physicians has narrowed.  Second, the reality that access to pre-approval treatments is not a bilateral agreement between patient and doctor could dissuade doctors from fully engaging in the process of gaining access.  Industry buy-in, health insurance cost uncertainty, and potential government regulation (albeit streamlined) are all factors that can influence the final outcome of a request. And, perhaps, as a result of the many players involved, clinicians do not feel it necessary to waste a patient’s time (or their own) on an effort that looks less like treatment and more like meeting of the United Nations.

So how do ALS clinicians address this conflict with the Joes and Joannas that ask them about access to unapproved drugs in clinic?  The Symposium did not offer a forum or a panel to address this question directly, nor did it present itself as the time and place for any form of debate.  Indeed, it is my understanding that the 2018 event was the first occasion to scratch the surface of these issues in the Symposium’s history.  That’s unfortunate, because I think clinicians would benefit from at least hearing where others fall on a spectrum of relevant questions, for example: Does the clinician’s view on pre-approval access depend on the patient’s progression rate, age, maturity, gender, or other factors?  If so, what are they?  To what extent, if any, do caregivers’ perceptions play a role in a clinician’s decision?

There is no “right” answer to any of these questions, just as there is no right answer for Joe’s attorney.  But the goal of a session to discuss these issues would not be to identify a right answer or to cause a change in the mindset and approach of clinicians worldwide.  Indeed, the purpose of a symposium is not to achieve uniformity in approach or medical judgment but rather to discuss, debate, and share a variety of views.  A clearer discussion of clinicians’ outlook on drug access—beyond the merits of the drug in question—could inform those clinicians who are uninformed or unfamiliar with the available avenues for unapproved treatments.

After all, shouldn’t all clinicians be ready in case the next Joe walks through their doors tomorrow?

 

[1] Zitrin, Langford & Tarr, Legal Ethics in the Practice of Law, 3d ed.

[2] Judith L. Maute, Allocation of Decisionmaking Authority Under the Model Rules of Professional Conduct, 17 Univ. Cal. Davis L. Rev. 4, 1049, 1050 (1984)

Invasive Ventilation and Ineffective Placebo Arms

Author: Stephen Finger, Ph.D., ALS/MND Patient Fellow

ALS/MND Patient Fellows Dinner

Some of my fellow ALS/MND Patient Fellows and and the Selection Committee members gathered for a meet-up and dinner together before the official start to the International Symposium in Boston.

Attending the International Symposium on ALS/MND in person, it was humbling to see 1,300 plus  attendees committed to improving the lives of people living with ALS and searching for a cure. In talking with clinicians, researchers, doctors, and advocates, I did not meet a single person who was not absolutely committed to this community. It was clear that these folks were not there because of their job, but were there because of their mission. Whether they were involved in clinical research to find out whether compounds might impact the disease, basic science to improve our understanding of the disease, epidemiological studies to generate future hypotheses, therapeutic methods to help us lead fuller lives while living with the disease, or developing technology to change what it means to be disabled, these people were devoting their careers to helping me and my family. If I could only list one take away from the weekend it would be that. 1,300 people doing everything in their power for me, my friends, my wife, and our kids. That is never taken lightly.

However, no one is stopping me at one take away, so read on if you wish….

After three days of nonstop presentations and reading about hundreds of additional posters, it is hard to distill down what I learned. I think what is most exciting about the research landscape right now is the diversity of approaches. Researchers continue to race up the learning curve and are attacking the disease from a number of different directions. Neuroimaging, genetic discovery, telemedicine, antisense therapies, brain interface, induced pluripotent stem (iPS) cells, machine learning… While the opening session stressed how much we still do not know, it is incredible how fast we are filling in gaps. If you are interested in reading about these ideas, I encourage you to scan through the program here.

One of the purposes of the ALS/MND Patient Fellows program was to make sure the patient perspective was not lost in the scientific proceedings. Overall, I was deeply impressed by how connected most of the discussions were to the patient experience. In hindsight, I think there were two areas where the patient voice could have been stronger: invasive ventilation and ineffective placebo arms in trials.

Stephen Finger ALS/MND Patient Fellow

That’s me in one of the clinical track sessions during the three-day symposium.

Invasive Ventilation

Even with all of the exciting work that is going on and all of the people working around the clock to find a cure, the reality is we are still taking baby steps. We hope that some of treatments in the clinic may modestly slow progression. We hope that new approaches will enable us to have an impact on some subgroup of patients. These are not insignificant goals. It would be amazing if we could slow progress down by half. Four-to-ten years sounds a lot better than two-to-five. Patients surviving twice as long, means there would be twice as many of us around. However, we must deal with the reality that is today. Solely in terms of survival, no treatment or approach that was discussed at the conference is close to as effective at extending lives as invasive ventilation. Even with all of the complexity of the disease, patients die simply because their weakened diaphragms cannot pump enough oxygen in and out of their lungs. If a machine does it for you, you can live a long time.

The downside of invasive ventilation is that all of your muscles still die off, and you need someone to monitor your ventilator 24 hours a day to make sure it is clear and working properly. Many patients understandably choose to not go this route because they cannot imagine continuing their life attached to a machine for the rest of their life. However, many others have the motivation to go on and believe they could maintain a healthy quality of life on a ventilator, but cannot bear to impose the financial, physical and emotional burden on their families that goes with around the clock care. You either force a family member to give up the rest of their life to care for you 24 hours a day or you pay out-of-pocket for 24/7 care. Because of these factors, less than 10% of patients in the United States elect to go on a ventilator. In contrast, Japan’s national health service provides generous home health coverage and over 30% of ALS patients make the choice to go on invasive ventilation (Japan prevents patients from choosing to go off their ventilator once they go on it, which I believe prevents even more patients from going that route).

This is common knowledge in the community. Patients learn this early on and every neurologist understands it. However, I still think the topic of invasive ventilation should have remained a larger part of the conversation at the conference. Many clinical trials use time until “death or tracheostomy” to measure survival. They use Kaplan Meier survival curves and Cox hazard models to generate their analysis and it makes sense to use this definition when looking at the efficacy of a treatment. However, I think it may also lead us to lose perspective over the magnitude of the impact of a ventilator versus anything else we are considering. Nothing else can extend life by years for advanced patients. We measure the impact on survival of investigational products in terms of months. Sometimes weeks. Yet studies of patients in Europe show that among those who elect to have a tracheostomy, roughly 40% to 50% of patients choose to remain on their ventilator and survive longer than two years. When we grow accustomed to glossing over the statistics, we lose the political will to advocate for more generous health insurance coverage for care that could significantly extend lives.

When we compare the cost of providing the home health care needed to relieve the financial burden on families, it is no more expensive than a new drug. If patients received 100 hours a week of care, how many more would choose to go on a ventilator because it would no longer bankrupt their families or force a spouse to sit at their bedside? These patients would live years longer. Yet the cost would be about the same as the sticker price on a new drug in the rare disease space. I understand the need for drug companies to make money. I understand that high prices on new drugs attract more research. Pharmaceutical companies are making billion-dollar investments. We need more of them to do that in the ALS space, and that is happening. I have no problem with high drug prices. However, how do we rationalize covering $150,000 per patient per year for a drug that has a small effect, while not covering financially commiserate home care that would allow patients to live substantially longer? If there was a drug or a device that ensured an ALS patient could breathe 24 hours a day, researchers would declare it a game changer, patients would be ecstatic, insurance companies or Medicare would consider $150,000 a year a bargain… However, insurance coverage for paying a Certified Nursing Assistant (CNA) the same amount to do the same job is rarely discussed. Every researcher who includes a survival curve in their analysis should include a line for patients who go on a vent just to make sure we do not lose sight of what is possible for patients right now. I believe continuously reinforcing these ideas is necessary to generate needed momentum in the community to achieve real change that could immediately impact patients’ lives.

Ineffective Placebo Arms

The second area where I thought the patient voice could have been stronger was with regard to placebos. Patients are rarely excited about the possibility of receiving a placebo in a trial. When you enter a trial and endure all of the burdens that come along with the process (though it is exciting to see many researchers thinking creatively to minimize this burden), you selfishly hope that the treatment will help you out. Most trials require patients’ initial symptom onset to have occurred within the last three years. So once they are diagnosed, many patients are only able to enroll in a single trial before they “age out”. When your prognosis is two-to-five years and nothing currently on the market has a big effect, this may be your only shot. However, especially in ALS, many clinical trial participants are also eager to enroll to help further the search for a cure. You feel helpless, so here is something you can actively do. We do not have very effective means to measure the effectiveness of treatments, so an important part of the trial process is establishing an accurate baseline. To figure out if something works or not, you have to be able to estimate how trial participants would have progressed without treatment. Placebo arms are one way to try and get at this.

My concern is that in multiple presentations researchers made offhanded remarks about how maybe the placebo group just happened to progress slower than expected when explaining negative results from trials. As a patient, this was a huge red flag. In order to further the science, we reluctantly agreed to enroll in trials where there was a possibility we would receive a placebo, yet the trials were designed in such a way where we didn’t learn from our participation?!?! I don’t think the researchers truly realized what they were implying to patients who volunteered for their studies.

Perhaps including placebos is a necessary evil, but if that’s the case, let’s make certain that our placebo arms are accomplishing their mission. If we learn something does not work, fine, we move on. But we cannot repeatedly say we don’t trust our baselines that were established by a bunch of patients using their one shot to serve as the controls.

The biggest issue with establishing a baseline in ALS isn’t that there are oversized or unknown placebo effects, it is that people progress at different rates and even their own progression rate varies over time. There was session after session about heterogeneity and all the problems it presents and how much we don’t understand. Phenotypes, clinical presentation, genetic variation, etc.… So why are we basing this crucial part of our trial on how a small group of patients, who unfortunately got allocated to the placebo arm, happen to progress?

Researchers talk about finding a balance between having enough patients on placebo in order to conduct good science, while not having so many as to impose an undue burden on their volunteers. However, it does not have to be this way. We have thousands of data points from failed trials. We have tracked thousands of patients who participated in trials, but were on placebo. They thought they were being treated. Instead of reestablishing this baseline for each trial from scratch, let’s leverage what we have learned. If we believe there is a need for concurrent placebo controls in a trial, let’s at least supplement the data with a bunch of observations from people with similar characteristics so that our results aren’t dependent on whether one patient who ended up in the placebo arm happened to do better or worse than average. If we really want to move into the 21st century, let’s leverage data analytics to see how patients in each arm of the trial do compared to predictions of their likely progression based on patients on placebo from other trials. If you are super conservative, include this supplementary data to generate secondary endpoints. If you insist that stratification is the way to go, then stratify on a prediction of likely progression informed by thousands of data points, not a necessarily small number of characteristics that may crudely be associated with progression.

No matter what we do though, let’s ensure that patients are not using their one shot in vain. The only thing worse than finding out you were in the placebo arm, is finding out that you were in a placebo arm that was constructed in such a way that we didn’t learn anything from it. We showed up at repeated follow-up visits. We endured all sorts of tests. After all of that, researchers must ensure that we are playing a valuable role in the process.

NOTE: The above blog post was written by Stephen Finger, Ph.D., a person with ALS and ALS/MND Patient Fellow. Only minor edits were applied to it by a Selection Committee member prior to publication, mainly to remove shorthand or jargon originally used. The opinions expressed are Stephen’s and are not necessarily a reflection of those held by other Patient Fellows or Selection Committee members. To learn more about Stephen or to contact him, click here.

 

Introduction to Virtual Fellows and addition of Andrea Peet

Being diagnosed with ALS makes it hard to plan really far into the future. The following two individuals applied and were selected to serve as Patient Fellows this past June, however, due to a variety of factors, they informed the Committee that they were unable to attend the Symposium in person just a short few weeks out from the event. Both Andrew and Steph have had an immense impact on the execution of this program and keeping them involved directly in it going forward will only add to our ability to achieve the mission of the Fellowship. Therefore, the Committee asked them to stay on with the group as “Virtual Fellows” and they agreed.

At the same time, the Committee discussed the ability to invite a person with ALS to join the other Fellows in Boston. With such short notice, it was going to be a difficult task. However, thankfully, Andrea Peet emerged as a person with ALS that met the criteria and was also able to swiftly commit to the parameters of the Fellowship. The Committee welcomes Andrea Peet to the ALS/MND Patient Fellows Program. You can learn more about Andrea Peet and all Patient Fellows here.

Meet the 2017 Patient Fellows

This year, the following six individuals living with ALS will act as Patient Fellows during the ALS/MND International Research Symposium taking place in Boston this December. The selection committee received two dozen applications and narrowing it originally down to three Fellows. However, thanks to additional funding being secured (in large part because of the high quality of applications received) the Committee was able to extend three additional invitations, doubling the size of the Fellowship Cohort for 2017.

Steph Courdin

I was diagnosed in 2013 with ALS while working for a software company focused on Mobile analytics, I became acutely aware of the lack of progression and wellness tracking for patients and instinctively knew something better than a 20yr old subjective survey was needed to scientifically measure progression and so we set out to develop a FREE app to empower patients and their care teams.

Prior to ALS, I spent 24+yrs in data analytics and performance management working for Cognos (acquired by IBM) and then Roambi (acquired by SAP) working with fortune 500 companies , as well as president and co-founder of Information Integration a BI & DW consultancy for 8yrs. I was an avid mtn biker , snowboarder and volunteer wrangler and photographer at Westernaires ( a volunteer youth equine organization with 1000+ members).

Stephen Courdin is CEO & Co-founder of ALS NeverSurrender Foundation (100% volunteer led non-profit).

Stephen Finger, Ph.D.

Stephen Finger was diagnosed with ALS in 2013. A vocal advocate, his articles have appeared in the Huffington Post, he appeared on the BBC and he actively participated in drafting the FDA Guidance Document. He serves on the Board of Advisors for the Every90Minutes Foundation and is on the Board of Directors of HopeNow4ALS. He was awarded the 2014 Stephen Milne Adventurous Spirit Award by the ALS Therapy Development Institute.

Stephen grew up in Arlington, VA. After earning degrees from Princeton and Duke, Dr. Finger was an economics professor at the Moore School of Business at the University of South Carolina. He now resides in Atlanta, GA with his wife Cara and their two kids, Mary Adair (7) and James (5).

Andrew Niblock

Andrew Niblock is the Director of Schoolwide Initiatives and the former Head of Lower School at the Greenwich Country Day School, Greenwich, CT. Prior to his current position he was the Director of Lower School at Hamden Hall Country Day School and spent eleven years as a teacher, coach and administrator at Isidore Newman School in New Orleans.

In July 2016 Andrew was diagnosed with ALS. In the time since, Andrew and his family have become more hopeful, not less. Andrew’s life’s work is education, and this is the lens through which he views ALS.

There has never been a more exciting time in ALS science. The creativity that comes with looking at problems from different angles, collaboratively, and with unprecedented advances in technology, gives justified cause for hope.

Sue Pondrom

I was diagnosed with Bulbar-onset ALS in March 2017.  My speech is almost gone, but I can still walk and I have limited use of my hands.  My career has included newspaper reporting, magazine editing, hospital public relations, and freelance medical writing.  But, the highlight of my life has been my husband, Ron (married 50 years this past August), my three adult children and five grandsons.

After receiving a bachelor’s of journalism degree at the University of Missouri, I was a reporter for newspapers in Missouri and Virginia.  When my husband finished his military obligation, we moved to California with one-year-old daughter, Lisa.  That seemed as good a time as any to have our second and final child.  We even followed the instructions in a book called “How to Choose Your Baby’s Sex” to try for a boy.  As one friend noted, we obviously didn’t read the fine print.  Our twin boys were born the day after Christmas.

In San Diego, I became a researcher, then copyeditor for Psychology Today magazine until it moved to New York. Rather than return to time-intensive news reporting, I began a 28-year career in public relations and medical writing.  My favorite PR jobs were with Scripps Clinic and Research Foundation, ScrippsHealth (five hospitals in San Diego County), and University of California, San Diego (UCSD) School of Medicine and Medical Center. After I “retired” from UCSD, I wrote freelance medical articles for publications such as Arthritis Today, The Rheumatologist, ENT Today, Neurology Today and various UCSD publications.  I am most proud of the eight years I wrote a monthly two-page news-feature section in the academic American Journal of Transplantation.

Meg Macdonald

In high school, I was Editor in Chief of my weekly newspaper. I moved on to study Geology in college and graduate school. When the job market failed me, I worked in various jobs such as delivery truck driver and office equipment salesperson before going back for a second master’s degree in hydrogeology and then working in groundwater issues related to the gold mining boom of the 1990’s in Nevada. Then after being a stay at home aunt and mom, I worked as an Administrative Secretary at a large public elementary school, a job I loved. I continued my love of writing with a blog about bicycling. I trained hard for a Ride to Defeat ALS ride, because I have ALS in my family.

My mom, my aunt, and my cousin all died from ALS. My own symptoms of ALS started in December of 2015. It started with slurred speech. My diagnosis was confirmed in June 2016, on the day before my 56th birthday. By August, I had a feeding tube and soon took no food by mouth. My speech declined and I had to become proficient with text to speech to keep working until November 2016. Starting right after my diagnosis, I turned my love of writing into a blog about living with ALS. My husband and my 17 year old son are my copy editors.

My mother was confirmed to have the C9ORF72 gene expansion, so when I had my DNA tested, I was not surprised that I have it too. This gene mutation can cause ALS or Frontal Temporal Dementia (FTD). There are many cases of FTD in my family also. I am participating in three research studies for the C9ORF72 gene mutation, one for biomarkers and another studying the FTD aspect of the gene mutation, plus one to look at my spinal MRI to try develop another way to diagnose ALS. I am committed to doing whatever I can to move this devastating incurable disease to a curable one.

Vic Walker

I am a pharmacist, board certified in psychiatric pharmacy. I worked for the State of California for 31 years in various clinical and administrative capacities. Most of my career was spent at Medi-Cal (California Medicaid), where I reviewed drugs for addition to the formulary and designed a good deal of Medi-Cal’s electronic pharmacy claims processing system. For the final eight years before my retirement, I created and led the Pharmacy Analysis Group within Medi-Cal. We worked with Medi-Cal’s massive claims database to do research, looking for areas of potential care improvement, as well as detecting fraud and abuse. I retired in 2012.

I have Primary Lateral Sclerosis (PLS). I had my first fall in 2001 (while attending a health conference.) The progression has been slow. I first saw a physician about neurological problems in 2003, but was not diagnosed till 2004, as a second opinion. I walked without a cane until 2010, and without a walker until 2015. I do not, as yet, need a wheelchair or scooter, except for times when I must walk a lot (e.g., Disneyland).

I retired from practice in 2012, and traveled to Taiwan for a year and a half, where my wife and I lived. We returned in 2013, and have been largely retired since then. We enjoy travel by car and airlines. I still drive, though I will be the first in line to buy an autonomous car when they become available. I am happily married, with four adult children and seven grandchildren. My wife and I both speak Mandarin Chinese pretty fluently, and I practice it every chance I get.

NOTE: Fellows wrote and submitted their own bios. 

 

Got ALS? Want to influence science? Good, we want you to do that as well!

What would happen if we opened up science meetings in ALS to people with ALS more? Would it improve relationships and communication between people with ALS and ALS researchers? Would people with ALS and researchers gain new perspectives on what they each are thinking about? We want to find out! That’s the idea we are exploring through this program!

All ideas start somewhere, and you can read how this one started and who is behind in in the About Section of this website.

There are links about regarding the Fellow Application and Selection Process as well as a lot of information about What Fellows Should Expect from this program (spoiler: lots of help!)

Thanks for your interest in this idea. We are really excited about its potential. Look forward to seeing everyone that can be at this year’s International Symposium on ALS/MND in Boston December 7, 8 and 9.

-Sincerely,

Cathy, Rob, Paul, Gudjon, Eric and Stephen

(aka The ALS/MND Patient Fellows Selection Committee)

Start your Patient Fellow Application