Dale Schenk, 59, Pioneer of Alzheimer’s Immunotherapy
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Dale Schenk, a leader in the field of Alzheimer’s disease immunotherapy passed away Friday, September 30, after a battle with pancreatic cancer that started in 2014. Schenk had been working until recently. He was 59.
Dale Schenk at the Siemans Foundation in Munich, 2006. [Courtesy of Christian Haass.]
Colleagues remember Schenk for his pioneering work developing immunotherapy for Alzheimer’s, Parkinson’s, and other amyloidoses. While at Elan Pharmaceuticals, San Francisco, Schenk’s seminal work showed that immunizing PDAPP transgenic mice with an experimental Aβ vaccine reduced the accumulation of amyloid plaques in their brains (see Jul 1999 news). This was the first high-profile paper raising hope that immunotherapy could potentially work in Alzheimer’s. It landed Schenk on the MacNeil Lehrer News Hour and other national media programs at the time.
This work led the way to AN1792, the first immunotherapy against Aβ to enter clinical trials. While AN1792 was halted in Phase 2 due to inflammation in the brain, Schenk’s vision galvanized the field and paved the way for dozens of active and passive immunotherapies that have since been tested in the clinic. He went on to develop therapeutic antibodies for AD (see Mar 2005 news), and, as co-founder and CEO of Prothena Biosciences, immunotherapies for other amyloidoses including Parkinson’s disease. Schenk explained the extraordinary advances in immunotherapy for HBO’s “The Alzheimer’s Project” (see Films About Alzheimer’s and click on the sixth icon at the bottom to load his interview). It is no accident that when Schenk won the American Academy of Neurology’s Potamkin Prize in 2001, he was the first industry scientist to be recognized.
Alzforum writers remember Schenk for his wry humor and his generosity. Whenever asked, Schenk made time to explain evolving concepts and interpret new data. During a period of intensive focus at Alzforum on autosomal-dominant AD in 2006, Schenk was the industry researcher most willing and able to articulate the promise of secondary prevention trials of investigational therapies in genetic forms of disease. A decade ago, when many industry scientists dismissively said, “Nice idea, but here is why it can’t be done ….,” Schenk acknowledged the potential of the paradigm, seriously considered its challenges, and then called them all “surmountable.” (See Early Onset Familial AD section, “Devil in the Details,” “Drug Trials in Early Onset AD,” and “Clinical Trials: Why Are eFAD Patients Excluded? Will That Change?”). As so often, he was right. Such trials are now up and running, and more being planned.
Alzforum will miss Dale. We invite friends and colleagues from years past and present to share memories, photos, anecdotes, thoughts to celebrate his life and work by emailing gstrobel@alzforum.org.—Tom Fagan, Gabrielle Strobel
Two giants of Alzheimer’s research, Leon Thal (L) and Dale Schenk, at the Alzheimer’s centennial meeting in Tuebingen, Germany, in 2006. [Courtesy of Jacqueline Mervaillie.]
[Courtesy of James Travis.]
[Courtesy of Gurik Basi.]
With Christian Haass in 2006. [Courtesy of Christian Haass.]
What Dale always cared about … [Courtesy of Prothena.]
Dora Games and Dale Schenk in 2012. Courtesy of Eliezer Masliah.
On a road trip to Melbourne. “Dale always picked up the check,” Guriq Basi said. [Courtesy of Guriq Basi.]
References
Research Models Citations
News Citations
Basic page Citations
Book page Citations
- Devil in the Details—The Challenges of Prevention Trials
- Drug Trials in Early Onset AD
- Clinical Trials: Why Are eFAD Patients Excluded? Will That Change?
Other Citations
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Co-Director, Brigham and Women's Hospital's Ann Romney Center for Neurologic Diseases
In Memoriam – Dale Schenk
September 30, 2016, was an incredibly sad day for me personally and for so many other scientists, physicians, and biotechnology enthusiasts around the world. We lost Dale Scheck to cancer at age 59. This visionary pioneer in the fields of human neurodegenerative disease and immunotherapy had devoted 30 energetic years of his life to the quest for transformative treatments for Alzheimer’s disease, Parkinson’s disease, systemic amyloidosis, and other disorders of protein folding and cell trafficking. In essence, he originated the field of immunotherapy of chronic brain disease and then applied it to other disorders in which the immune system could be harnessed to potentially cure suffering. Beyond that truly seminal work, Dale performed or directed myriad scientific experiments to understand the relationship of fundamental biological processes to the mechanisms of disease.
I met Dale 30 years ago in a coffee shop at San Francisco International Airport. Larry Fritz, Dale’s colleague at Calbiotech at the time, introduced us, and I fell in love with Dale at that first meeting. Dale impressed me as very bright, thoughtful, and yet disarmingly warm and personable. At the time, I was collaborating with Larry and with Kevin Kinsella, an inspired venture capitalist in the biotechnology arena, to found Athena Neurosciences, arguably the world’s first biotechnology company devoted strictly to brain disease. Larry had recently become Employee No. 1 at Athena, and my interview with Dale quickly convinced me that Larry was right: Dale must become Employee No. 2. Now all these years later, Dale Schenk stands out among our talented recruits in those early days: the inspired scientific leader who rose to the top at Athena and at Elan, which acquired Athena in 1996, later going on to co-found Prothena Biosciences, the smart and innovative company that he led as CEO until his tragically untimely death.
Dale thought deeply about unsolved problems in biomedicine. He brought his knowledge of protein biology and immunology to bear on Alzheimer’s disease in a way that has already transformed the development of treatments for that complex disorder. The recent publication of an article in Nature from Biogen describing the striking clearing of amyloid plaques in humans with mild AD using a monoclonal antibody, accompanied by an apparent slowing of cognitive decline, represents the latest and strongest evidence that Dale Schenk’s disruptive concept of immunotherapy against endogenous misfolded proteins could really work. Dale and I recently shared satisfying conversations about this success of his theory, even while acknowledging that further rigorous testing in the clinic lay ahead. At the end, Dale remained firmly convinced that immune responses to amyloid deposits in Alzheimer’s or AL amyloidosis or Parkinson’s could dramatically lessen the pace of progression in these terrible disorders and help many millions of people control their diseases. While he did not live to see the unequivocal validation of his innovation, I know he was thoroughly convinced that it will work, and I share his conviction.
I experienced for 30 wonderful years the privilege of working with Dale and his many beloved Athena colleagues—including Dora Games, Kelly Johnson-Wood, Pete Seubert, Ivan Lieberburg, Lisa McConlogue, Guriq Basi, Frederique Bard and Ted Yednock. I witnessed the warm bond he formed with his scientific colleagues at Prothena since he founded it in 2012—Wagner Zago, Dan Ness, Robin Barbour, Marty Koller, Ken Flanagan, and perhaps first and foremost, Gene Kinney, his “alter ego” at Prothena who, as chief scientific officer, has led the execution of Dale’s and his own ideas for modifying chronic diseases. These gifted researchers and many others whom space precludes naming were inspired every day by Dale’s intelligence, his drive to succeed, his loyalty and his friendship.
When he was not worrying about the march of biomedical science, Dale enjoyed the warmth of a wonderful family—his dear wife, Liz; his sons, Max and Sam; and his daughters, Anais and Sara. He often regaled them and his friends with his magnificent talent at the piano, something I had the privilege to hear in the quiet of his lovely house in the hills of the Peninsula. Dale was a formidable chess player, often jousting with Larry Fritz in the early Athena days, and he was a whiz at table tennis, even beating the formidable John Groom, Athena’s first CEO. I only once managed to best Dale at ping-pong, and that was after plying him with a fine bottle of wine (like Liz, he was an expert oenologist) after dinner at my house.
Through all of his varied professional and personal pursuits, Dale was almost always smiling, a man with a wonderful sense of irony and the ability to skewer fuzzy thinking (including my own) while still making one feel that he was the sweetest guy in the world. And that’s exactly what he was. I miss you, Dale.
Arizona Alzheimer's Consortium
Dale was a true pioneer in Alzheimer’s research. As head of R&D at Elan, he and his colleagues introduced the first transgenic mouse model of AD, the first amyloid vaccine and passive immunotherapy for Alzheimer’s, and other groundbreaking approaches to this problem. Since then, he founded, and made great progress in, another highly productive biotech company, Prothena.
At Banner Alzheimer’s Institute, Dale was one of our Leon Thal Memorial Lecturers. He exemplified the generosity of spirit that all of us hope to see in our industry colleagues. He was here in Arizona to meet with Francisco Lopera, Governor Napolitano, and me when the Alzheimer’s Prevention Initiative was but a gleam in our eye. Dale was always extremely supportive of our efforts here in Arizona.
If the amyloid hypothesis is confirmed, and anti-amyloid treatments turn out to have a profound impact on the treatment and prevention of Alzheimer's, then we’ll look back on Dale like Moses, for his leadership efforts to take the field to the “promised land.”
Dementia Reserch Center
I too feel very sad at this news. Dennis's comments entirely fit with my experiences of Dale. In all my interactions with him, he was always as generous and modest as he was insightful. His breadth of talents were remarkable. He will be greatly missed.
University of Southampton
There was late snow in Italy that spring. Mount Vesuvius, overlooking the Bay of Naples, was crowned with white, making it look like a child’s drawing of a volcano. A cold wind blew down its slopes and across the water to Sorrento, tempered by the sunshine already strong by that time of year. The AD/PD meeting in March 2005. One of a series of meetings which represented, for me, a very exciting time. Dale Schenk’s pioneering animal work in clearing plaques from the mouse brain by Aβ immunotherapy had been translated into human clinical studies. These had shown evidence of strikingly similar plaque clearance in the brains of patients with Alzheimer’s disease. This was perhaps the first alteration of Alzheimer’s brain pathology by a rationally designed therapeutic approach.
I first met Dale when he approached me at an Ipsen Foundation meeting in Paris. “I think you have some interesting news for me,” he said. I had just been examining the first brain histology of a patient who had been in the AN1792 trial. It was remarkable. I subsequently flew to visit Elan Pharmaceuticals in South San Francisco and sat down at the microscope with Dora Games to compare the human histology with the slides from their animal studies. It was immediately quite clear to us that the Aβ42 vaccine had essentially the same effect in both species. On the way to dinner that evening, Dale drove me along the start of Highway 1, roof down in his Porsche, overlooking the Pacific Ocean.
Over several years, at Dale’s invitation, I contributed presentations to multidisciplinary symposia on Aβ immunotherapy at conferences in several locations in the United States and Europe. These were followed by dinner with the speakers, leaders in this exciting field, and the atmosphere was heady.
I exchanged emails with Dale just a few weeks ago. I wanted him to know that some years later we are still gaining new information from the patients who had been in that first AN1792 trial, and hopefully this can be of some use to help guide and interpret current trials. He told me how positive he was about their studies of α-synuclein immunotherapy for Parkinson’s disease—looking forward.
Such a simple idea it seemed, and yet so many years later it still remains unclear whether Aβ immunization will be useful therapy, more likely perhaps prevention, for Alzheimer’s disease. This attests to the complexity of the situation when things go wrong with the human brain.
It was a privilege and a pleasure to know Dale and to have had some involvement in his pioneering work. A sad loss at such a young age.
Johns Hopkins University
I would like to thank Dennis Selkoe for his beautiful commentary on Dale. I was among Dale's colleagues along with Larry Fritz and others at California Biotechnology, "back in the day" when we were first working toward obtaining the first clones of APP. I lasted a bit beyond their departure when they joined Dennis and colleagues in the Athena adventure.
I recall the chess games between Dale and Larry that occasionally interspersed the working hours of the days. I recall Ivan Lieberburg joining our group to learn a bit of practical molecular biology, and how this trio went off to start that small company in South San Francisco that made such a huge impact on the field. I recall the laughter, humor, and good cheer among those fellows that was frequent amidst the hard work of the day.
We became competitors, but there was always a friendliness about it, and indeed the generosity that Dennis described so well when in later years I had occasion to see Dale and his colleagues when I would visit from another pharma company in search for a potential collaboration. It was with Dale in mind that I later shared with my colleagues that there is no such thing as a true competitor—just different degrees of collaboration, as we all join together in pushing the envelope of knowledge. Dale was grand at that.
I also recall other deeds Dale accomplished which Dennis may not have been aware of. Dale was the individual who performed the radioiodinations at Cal Bio. There was that day when he radioiodinated the entire room, which had to be closed down for decontamination. I followed in his footsteps by doing a similar deed some time later in our laboratory, except it was P-32. There are those moments in our careers which we don't recognize to be as special as they are until looking back through a retrospective lens.
I am saddened by this news of Dale's death, but wish to honor his memory and the impact he had on the field, and perhaps, just perhaps, the growth of that impact toward eventually creating a treatment that will make all of our careers ultimately successful. He will always remain among the special individuals to whom we owe our gratitude and respect.
RIKEN Center for Brain Science
It was 2003 when Takeshi Iwatsubo and I tried to visit Dale in San Francisco after the Society for Neuroscience meeting in San Diego. Because of heavy fog, the direct flight was cancelled, so we needed several hours to reach San Francisco via fragmented flights. When we finally arrived at San Francisco Airport, Dale was still waiting for us at the arrivals terminal, and looked so relieved to find us. He must have been waiting for at least four hours. He then took us to Athena, the company which he had originally started. He showed us his office and laboratory, emphasizing how small Athena was in the beginning. I still remember that Dale said, “I really hope it [immunotherapy] is going to work [in humans].” I believe this is the feeling every experimental scientist has when the basic research is being translated into clinical application. Dale was one of the sincerest scientists I know of.
I admired Dale as a brilliant scientist, and a genuinely likeable person to meet. In my own little world, I saw him as a friend.
Sincere condolences to Dale's family, friends, and all who worked with him at Athena, Elan, and recently Prothena.
I first learned about Dale in 2003 as a scientist at Elan Corporation. Over the years, it was so interesting to closely follow Dale's pioneering scientific approach.
Dale Schenk was my No. 1 neuroscientist.
Rest in peace my, friend.
Center for Regenerative Medicine
I met Dale in 1989, when he was at Athena and I was just joining GenPharm. He thought in a straightforward way and wasn't afraid to do something completely different. The experiments he did with Dora on the transgenic mice were crazy, inspired, and rocked the field.
A few years ago, I chaired his session at a conference, introducing him by telling the audience that all those trials using immunotherapy for AD started with him. Dale was amused. It was the last time I saw him.
Cognition Therapeutics Inc.
Dale was a true pioneer, and one of the bravest industry scientists in the field. He will be sorely missed.
University of Hull
We are missing Dale Schenk, the man who invented the research path of immunotherapy of Alzheimer's disease.
Emory University
I met Dale around 25 years ago, when the Alzheimer’s field was in an uncertain state. Researchers were seeking a clear path to disease modification, but many of the tools that would make this possible were still lacking.
Dale and I began a brief and gratifying collaboration to determine whether we could specifically target Aβ deposits in the living brain with monoclonal antibodies. Dale had some of the best such antibodies at the time, along with a wealth of expertise on their use. We found that antibodies delivered to the CSF could specifically label Aβ plaques and vascular deposits in aged nonhuman primates (one of the few models of cerebral Aβ-amyloidosis at the time), and concluded that Aβ antibodies might be useful for diagnostic and therapeutic purposes.
But for therapy, we were thinking of the antibodies mainly as delivery vehicles rather than as the therapeutic agents themselves. Dale then made this trailblazing leap, which he and his colleagues at Athena convincingly substantiated in a newly developed transgenic mouse model.
I clearly recall first hearing the news, in 1999, about Dale’s report in Nature that active immunization against Aβ could dramatically reduce cerebral Aβ load in the mice. For days afterward I even considered shifting my research to another disease, as it looked like the Alzheimer’s problem had been solved. Of course, the subsequent road to immunologic treatment of AD has been bumpier than anticipated, but recent clinical trials have increasingly validated Dale’s vision of immunotherapy for diseases of protein aggregation.
This concept gave new energy and a needed dose of optimism to Alzheimer researchers. Those of us who were fortunate enough to be his friends and collaborators certainly will miss him, but Dale’s scientific legacy will continue to inspire important research that could eventually yield an effective preventive or treatment for AD.
Ottawa Hospital Research Institute
I was deeply saddened to learn about the passing of this wonderful man. I will always remember Dale for wisdom he shared during two specific exchanges.
One took place in the presence of Ivan Lieberburg at a scientific meeting following their publication of the successful treatment of amyloidosis in the PDAPP mouse (Schenk et al., 1999). I had asked Dale and Ivan how the idea of active immunization against Aβ protein in mice as a potential treatment paradigm for Alzheimer disease had initially started, either at Athena Neurosciences or Elan Pharmaceuticals. My question made them both laugh, puzzling me. Ivan explained (to the best of my recollection) like this: “In years past, Dale had requested internal funds more than once to pursue this crazy idea of his, which was voted down repeatedly. Ultimately, we figured we can’t do this to him any longer, because everyone really liked him as a colleague. Therefore, we earmarked a small amount for him and his project, which we all thought would go nowhere. The rest is history … ” When I asked Dale how that had affected him as a person, he replied, still smiling, “It doesn’t matter today how it happened; if you believe it is a good idea, you just have to keep pushing and try testing it.”
The second occurred in the summer of 2001 or 2002 during a visit at Elan Pharmaceuticals over lunch, which we shared with some of his younger colleagues after a seminar I gave. We began talking about the hiring of young scientists, and I asked how he picked one qualified candidate over another applicant. “It is not difficult, Michael. I just look for the one who really cares about the human suffering,” Dale said. I must have looked befuddled (not expecting this reply) because he added, “If the candidate has shown me that there was a personal connection to a disease in his (her) life, it doesn’t have to be Alzheimer’s or Parkinson’s, I will always take that person, because I know that he (she) cares and will give his (her) best.”
To my mind, these two exchanges truly capture what our professional journeys in the medical sciences are all about. Dale was an inspirational scientist, a formidable builder, a charming host, a thoughtful listener, an excellent debater, and a true “mensch.” He will be dearly missed.
I hope we will celebrate Dale’s life and legacy at many upcoming events, such as at the AD/PD Conference in 2017.
References:
Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999 Jul 8;400(6740):173-7. PubMed.
Woodford Investment Management
In the field of fund management, I have the good fortune to meet some exceptional and impressive people, in all sorts of roles. As a long-term investor, I have the opportunity to form very strong relationships with these individuals over time, especially if I feel a personal affinity to them.
One such relationship for me, has been with Dale Schenk, co-founder and, until recently, chief executive of Prothena. I first met Dale about seven years ago when Prothena was still part of Elan and was immediately impressed by his passion, his energy, and his enthusiasm for his science.
It was with great sadness that I learned, late last week, that Dale had succumbed to the disease that he had been fighting over the last two years. Dale was an incredibly creative and determined scientist and business leader. He had the right motivations. He wasn’t just trying to build a business—he was driven by a desire to bring better therapeutics to patients suffering from awful, debilitating conditions. He wanted to make a difference and that is something that I found inspirational as an investor.
With Dale’s passing, we have lost a very talented human being, but it is important to reflect on what he has helped to build. Part of his great skill and insight was his ability to build a strong and gifted team around him—a team that is dedicated to continuing his groundbreaking work in the field of protein immunotherapy. Dale’s legacy will live on in the technology that we hope and believe will develop into successful therapies for patients with Amyloidosis, Parkinson’s disease and, potentially, many other conditions that remain poorly treated by modern medicine.
Our thoughts go out to Dale’s family, friends, and colleagues.
We all lost a very talented scientist, generous human being, great friend and devoted family man with the passing of Dale Schenk. I worked with Dale for more than 20 years, and it was a true pleasure. He had great insights, imagination, and a wonderful sense of humor. We had a core of researchers who loved working with Dale and stuck together for a couple of decades, a longevity most unusual for the industry. By any objective measure, his team made significant contributions against AD in areas including animal models, diagnosis, APP metabolism, and immunotherapy.
Dale was also a great leader in prioritizing and planning beyond the bench discoveries. We had to deal with a variety of challenges during our time together (it’s never a good sign when your adverse event/tox people are debating what to call something …), but Dale was unflappable and always dusted himself off and got back in the game. He was always strong in dealing with adversity, and many of us felt he would beat his cancer with, if nothing else, his character.
Very relevant to Alzforum was Dale’s embrace of the “Research Community.” In contrast to stereotypes about people in industry, he believed in collaboration and pushed the “company” side of our business to allow the sharing of results and reagents far beyond what was required or practiced by most others. He loved to host symposia to debate AD’s causes and treatments and often provided (against my advice) competitors and critics a spot on the stage, which is beyond what would have occurred to most of us to do. He realized that working with people outside our own needs and interests helped progress against the disease as well as providing a more unified consensus message of hope to patients, caregivers and policy makers. Hopefully his memory will inspire cooperation and generosity among those continuing the fight against AD.
He was truly more devoted to making meaningful contributions and progress against diseases than to padding his own personal status. People as bright and unselfish as Dale are a treasure, and his loss is a loss for us all. With a heavy heart, I say farewell to Dale.
Biomedizinisches Centrum (BMC), Biochemie & Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
As a postdoc in Dennis Selkoe's lab, and later as a group leader back in Germany, I had the pleasure and honor to collaborate on several major research projects with Dale.
Dale was one of the greatest and most visionary scientists I ever collaborated with. But he also was a great friend, always ready for help without any further questions.
Dale was a fantastic communicator for the general audience. I will never forget his electrifying lecture at the Siemens Foundation in the Nymphenburg Castle in Munich, which I chaired in summer 2006.
Now that immunotherapy may be so close to success, it is very hard to learn that Dale cannot see anymore the enormous impact of his pioneering therapeutic approach.
Dale, with your passing I miss a great friend and phenomenal scientist.
In 1987 I was the fourth employee to join Athena Neurosciences as its new CEO. Dale was already on board, having been lured away from Cal Bio by Larry Fritz. Over the 10 years or so that we worked together in San Francisco, he achieved so much. In the lab he was calm, composed, and very creative. Often his ideas were greeted with snorts from the other coats. Who else would have thought that immunization might be a valid treatment to slow or prevent AD? He was a fine leader of the teams that worked for him.
I truly regret not being able to attend the memorial service to say goodbye to a great guy.
It is a truth universally acknowledged (as Jane Austen would say) that Dale B. Schenk was a revolutionary scientist and a gem of a human being. There are and will be many tributes to his extraordinary scientific mind and his indelible impact on the science and treatment for devastating diseases. But sometimes other memories form crystalline images that capture the essence of a personality.
I would like to share just one of so many of these memories that I have of Dale. We were on a bus in Kyoto, Japan, setting out for a day of serenity and visiting temples. A bewildering array of buttons with mysterious symbols were embedded in the back of the seat facing us. Out of the corner of my eye, as if in slow motion, a finger floated by, targeting a particularly interesting one of them. I thought “Oh, no. Dale, NO!” Sure enough, the bus screeched to a stop, and all the other, mostly Japanese, passengers stared at us. Dale had, of course, pressed the emergency stop. His mischievous curiosity just couldn’t resist the urge to see what would happen. He disarmed everyone with a big, goofy laugh, the whole bus joining in.
With that same irrepressible spirit, Dale pursued immunotherapy as a novel therapeutic for CNS disease—he wanted to see what would happen and he surprised the world. He created a unique corporation with a commitment to discovery that nurtured both seasoned and young scientists. He loved his delightful children and his wife, Liz, who made him exuberantly happy. All around him he wove a beautiful tapestry of humor and work, and it was an audaciously bold pattern. We who had the privilege to share our lives with him will always carry his magnificent spirit with our own.
Uppsala University
I first meet Dale in 1992. He contacted me when we published the Swedish mutation, and invited me to give a lecture at Athena Neurosciences in San Francisco. Being new to the field, it was very important for me to collaborate with Dale and the researchers at his company.
When he published the Nature paper on immunotherapy in 1999, we had recently found the Arctic mutation, and seen its propensity to form large soluble protofibrils of Aβ. His paper inspired me to develop an antibody targeting this species of Aβ, now in a large clinical trial for Alzheimer’s disease. With Dale Schenk's death, the field has lost a great scientist.
UGA
I first met Dale Schenk more than 30 years ago when he invited me to act as a consultant for Athena Neurosciences (later to become a part of Elan Pharmaceuticals). The company had begun a study to determine the mechanism(s) by which APP was both normally and abnormally processed. The long-range plan was to characterize the enzymes (secretases) involved and develop drugs to inhibit the rogue enzyme (β-secretase) and thus reduce plaque formation in the brain, a hallmark in patients with AD.
Dale recognized immediately that this would take considerable time and embarked on a revolutionary path to develop a vaccine against APP fragments, which would also eliminate plaque formation. Until then, no one had considered such an approach, but Dale and his team carried on, ultimately finding an antibody that could, in a rat model, eliminate plaque. When the antibody program was later applied in a clinical study the results, while disappointing, suggested that a vaccine would likely only work in patients who could be diagnosed in the early stages of dementia. Because many other diseases are at least partially a result of protein aggregation, including systemic amyloidosis and Parkinson’s disease, Dale’s unique and original vaccine model for AD treatment is now being considered as an approach to removing these protein polymers as a possible cure.
These are not at all easy problems, and during my visits to San Francisco the one thing I noticed was that all of Dale’s staff loved working under his guidance. Laughter was common in the laboratory as Dale took a hands-off approach, letting the science lead the way. His attitude was that there was never a failure when an experiment went awry. Rather, he pointed out, the results would always tell you what other avenues to take. He showed remarkable patience, despite the fact that John Groome, Athena’s CEO, was always asking Dale for results, mostly tongue in cheek.
Dale was an extraordinary individual in that he was not only an expert scientist but also excelled at chess, piano, and, of course, ping-pong. However, what may not have occurred to others was his wry sense of humor. I remember giving a seminar at Athena/Elan when a major earthquake occurred. Being from California, Dale took it all in stride, first telling me that my talk was “earth-shaking” and then, when I was unable to return to my hotel, putting me up at his condo, all the while reminding me that the San Andreas Fault line was only a few hundred yards away. When the building shook in the middle of the night, Dale told me to go to sleep, reminding me that these were just aftershocks. He constantly reminded me about how I had reacted to the quake, only relenting after he had brought me home from dinner on a subsequent visit, and turned into a weigh station off the freeway instead of an exit ramp. We were now even.
As we got to know each other better over the years, visiting with our spouses at each other’s homes, I began to feel like I was talking to a younger brother. We could discuss almost any subject, not always agreeing but always learning from each other.
When he told me he was diagnosed with pancreatic cancer I was devastated, knowing all too well that the survival rate was less than 5 percent. We kept in touch as much as possible, with Dale and Liz coming to Athens, Georgia, for my 80th birthday despite his ongoing battle. That was the last time we met, although we continued to discuss science, our families, and our health by phone and/or e-mail up until the last few weeks.
I was extremely fortunate to have a friend like Dale Schenk. The rest of the world should be so lucky. He was an extraordinary human being whom I miss dearly but will never, ever forget.
Dale Schenk, Renaissance Man
Dale was a talented and accomplished man who excelled in many aspects in life, but above all as a friend. Dale belonged to that generation of scientists who heralded a new era for research and therapeutics for Alzheimer’s disease and related disorders. But he was also a composer, classical pianist, flamenco dancer, loyal colleague, and a beloved friend and family man who, with his amazing sense of humor and enthusiasm, brought together the best people and science. He was always kind and positive, as a person and with his science.
At a time when interactions between industry and academic scientists were sporadic and limited, Athena Neurosciences, thanks to Dale and his colleagues, became the leader in the field at developing collaborations that led to remarkable discoveries. But above that, Dale’s personality and generosity opened the doors to the closer and more meaningful interactions among scientists in private and public institutions that it is now a model in the field.
My group at UC San Diego, with Lennart Mucke first at The Scripps Research Institute and later on at the Gladstone, started to collaborate in the early 1990s with Dale, Dora Games, Lisa McConlogue, Pete Seubert, and many others at Athena to develop novel models of Alzheimer’s disease. Our friendship and scientific collaborations remained active and strong until his last day.
The development of immunotherapy for synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies is another example of the power of bringing together folks in academia and industry. It was at an SfN meeting in San Diego in 2001 that Dale and I sat at a coffee shop (his favorite place) next to the Pacific Ocean and drew, on a napkin, the concept of how a potential synuclein vaccine might work. Those were the good old days, and little was known about synuclein and Parkinson’s. Moreover, people strongly doubted the potential use of a vaccine approach in Alzheimer’s and even more so in Parkinson’s. Dale was one of the few who listened and believed in the idea.
Ed Rockenstein and I worked closely with Dale, Dora, Lisa, Pete, and many others, and later on with Wagner Zago at a company that Dale started to develop immunotherapies targeting synuclein. At the time it was known as Neotope Biosciences and later became Prothena Biosciences. One time I heard Dale say that he named the new company Prothena to convey both misfolded Proteins and Athena. He wanted for the new company to keep a strong tradition of collaborations between biotechnology companies and universities, as was the initial impulse for Athena Neurosciences in the early 90s.
The last time Ed and I visited Dale and the rest of the team at Prothena, including Gene Kinney and Wagner, was in the spring of 2016. It was a beautiful day in South San Francisco, and Dale looked strong. I had made the decision of moving to the NIH-NIA, and as always with a smile and wholeheartedly he wished me well. I’m going to miss him very much and will always remain grateful for the blessing of getting to know him. A true inspiration for all of us.
Prothena
I was privileged to work for Dale and call him my friend for 29 years. He and I had a running disagreement on my office. Dale was an everything-in-its-place type, I am more of an organized-chaos person. For all the years we would good-naturedly tease each other over our differences. This was one of Dale’s strengths, his ability to form a connection with everyone he worked with, whether over messy offices, a killer game of table tennis or love of cars. Dale always walked around with a smile, and if he was visiting the labs usually he was stopping by to joke about helping run a Biacore assay or purify an antibody because he missed the lab. We would all tease back that our timelines couldn’t afford it, and he would agree with a laugh and move on.
Dale approached everything with an intensity most don’t have; whether it was science, table tennis, or his fight against cancer, he was all in. He passed this attitude on to each of us who worked with him, and in conversations with friends who have moved to other positions, “Dale made me a better scientist” was a reoccurring comment.
My thoughts are with Liz and his kids on their loss. Dale was very much a family man, too. His kids shared his passion for life. One of the funny stories was during bring-your-kids-to-work day, when Max took the rocket from his dad after he could not get it to launch and told him, “This is how you do it.” Dale valued the family time of his co-workers and what that brought to their lives. I hope we can find some comfort in knowing how many people Dale touched in his life, and how many patients’ lives will be changed in the future because of his commitment. I will miss him and his good-natured teasing every day.
Vice President, The Institute for Molecular Medicine
Yesterday, I learned that Dr. Dale Schenk had died at age 59. It is sad news that his passing came at a time when he was in his prime. Through the present day, he has been making such tremendous contributions to his field.
Dr. Schenk was a pioneer in the areas of immunotherapy and neurodegenerative disorders. His first article in Nature inspired many scientists to embark on researching diseases associated with the brain.
Prior to his groundbreaking work, the possibility of passive or active vaccinations against neurodegenerative disorders was considered entirely not feasible. After his research, many scientists began exploring Alzheimer’s, Parkinson's, and other neurodegenerative disorders. My collaborators from IMM and UCI and I began working on immunotherapy in 2001 thanks to Dr. Schenk’s studies. To this present day, all of Dr. Schenk’s work and work associated with the Elan Corporation are still the scientific and ethical standard that we follow.
GSBio, LLC
I had the privilege of working with Dale at Athena Neurosciences and Elan from1992 until the genesis of Prothena in late 2012. Over this time period, Dale was at varying times my supervisor, colleague, mentor, and psychiatrist. However, at all times, Dale was, to myself and everyone else he worked with, a friend. Dale is best known and remembered for his seminal work demonstrating immunotherapy as a treatment for Alzheimer’s disease, but he did so much else, too. I would like to recount some of Dale’s contributions to AD research beyond immunotherapy during the time I knew and worked with him at Athena and Elan.
At the time of my joining Athena, Dale was heading up our efforts to develop a diagnostic test for AD. During the course of this effort, the team at Athena was at the forefront of landmark discoveries in the field, from the detection of secreted Aβ in biologic fluids (Seubert et al., 1992) (with implications for APP processing enzymes, Oltersdorf et al., 1990; Seubert et al., 1993) to demonstrating the relationship between Aβ42/40 ratio and tau in CSF as biomarkers of disease (Vigo-Pelfrey et al., 1995; Motter et al., 1995).
Subsequently, Dale oversaw the “ABR” (Aβ reduction) project, a part of Athena’s broader AD research partnership with Eli Lilly and Co., which led to the discovery and development of Semgacestat and the forerunner of Elan’s γ-secretase project. Under Dale’s leadership, the Athena team discovered the widely used γ-secretase inhibitor DAPT from a cellular screen for Aβ-lowering compounds, and used it to demonstrate the first proof of concept for in vivo reduction of Aβ by targeting the enzyme involved in Aβ production (Dovey et al., 2001).
The convergence of multiple lines of investigation, culminating with the identification of PS1 and PS2 as the catalytic components of γ-secretase (Wolfe et al., 1999; Li et al., 2000), marked significant milestones in AD research. I recall our discussing the implications of a report by Struhl and Adachi on the requirements for PS-dependent Notch cleavage for discovery of APP-selective γ-secretase inhibitors. Dale immediately, and presciently, concluded that γ-secretase was likely analogous to α-secretase, another “lawn mower protease of the cell membrane,” revealing his knack for injecting levity when prospects looked dim.
Indeed, Dale’s tendency to balance challenging times with levity kept the research environment at Elan healthy and positive through many a tough time. Phrases such as “Let’s just Schenk it” (for pursing both options simultaneously instead of “A” over “B”), “What could go wrong,” and “Gee … it seemed like a good idea at the time” became part of the lab vernacular there.
In summary, Dale Schenk’s contributions impacted AD research well beyond immunotherapy. His insight, curiosity, humor, and presence will be dearly and sincerely missed in the AD community.
References:
Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature. 1992 Sep 24;359(6393):325-7. PubMed.
Oltersdorf T, Ward PJ, Henriksson T, Beattie EC, Neve R, Lieberburg I, Fritz LC. The Alzheimer amyloid precursor protein. Identification of a stable intermediate in the biosynthetic/degradative pathway. J Biol Chem. 1990 Mar 15;265(8):4492-7. PubMed.
Seubert P, Oltersdorf T, Lee MG, Barbour R, Blomquist C, Davis DL, Bryant K, Fritz LC, Galasko D, Thal LJ. Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide. Nature. 1993 Jan 21;361(6409):260-3. PubMed.
Vigo-Pelfrey C, Seubert P, Barbour R, Blomquist C, Lee M, Lee D, Coria F, Chang L, Miller B, Lieberburg I. Elevation of microtubule-associated protein tau in the cerebrospinal fluid of patients with Alzheimer's disease. Neurology. 1995 Apr;45(4):788-93. PubMed.
Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clark C, Green R. Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol. 1995 Oct;38(4):643-8. PubMed.
Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ, Hu KL, Johnson-Wood KL, Kennedy SL, Kholodenko D, Knops JE, Latimer LH, Lee M, Liao Z, Lieberburg IM, Motter RN, Mutter LC, Nietz J, Quinn KP, Sacchi KL, Seubert PA, Shopp GM, Thorsett ED, Tung JS, Wu J, Yang S, Yin CT, Schenk DB, May PC, Altstiel LD, Bender MH, Boggs LN, Britton TC, Clemens JC, Czilli DL, Dieckman-McGinty DK, Droste JJ, Fuson KS, Gitter BD, Hyslop PA, Johnstone EM, Li WY, Little SP, Mabry TE, Miller FD, Audia JE. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem. 2001 Jan;76(1):173-81. PubMed.
Wolfe MS, De Los Angeles J, Miller DD, Xia W, Selkoe DJ. Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease. Biochemistry. 1999 Aug 31;38(35):11223-30. PubMed.
Li YM, Xu M, Lai MT, Huang Q, Castro JL, DiMuzio-Mower J, Harrison T, Lellis C, Nadin A, Neduvelil JG, Register RB, Sardana MK, Shearman MS, Smith AL, Shi XP, Yin KC, Shafer JA, Gardell SJ. Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature. 2000 Jun 8;405(6787):689-94. PubMed.
Struhl G, Adachi A. Requirements for presenilin-dependent cleavage of notch and other transmembrane proteins. Mol Cell. 2000 Sep;6(3):625-36. PubMed.
UCB Pharma Belgium
I was deeply saddened by the loss of Dale Schenk, a great pioneer of modern AD research and drug discovery in neurodegeneration. Dennis’ In Memoriam captures Dale and his extraordinary contributions perfectly.
Since the early '90s, I had the chance to discuss with Dale secretases, α-synuclein therapeutics in PD and, of course, Aβ immunotherapy. Dale was always science-based, thoughtful, often visionary. At conferences, he was always patient with challengers, some of who had not even read his papers. He was unafraid of any dogma.
Dale will be deeply missed by his friends, colleagues and competitors.
Various
In a world of few leaders with courage, the stamina to achieve something truly significant, and the ability to inspire others to both believe in what's possible and join in the effort to achieve that possibility, we've lost one of those rare individuals with the passing of Dale Schenk.
No doubt that Dale was a talented and inspiring scientist. His thought leadership, ability to take chances, and solve the previously unsolvable were forever present in his professional life and conduct. His success in explaining complexity in concrete terms was amazingly valuable, as taking the science forward often meant explaining to non-scientists what the route was and why it was worth the risk.
He was a good and caring husband and a devoted and loving father in an increasingly complicated world. Dale had a world-class sense of humor, with an ability to laugh first and foremost at himself.
I was fortunate to spend a decade working with Dale while at Elan. That—as it turned out—was not nearly enough time. We owe it to Dale to give it everything we have to complete his vision of what is possible, and make a quantum leap in progress against neurological/protein folding diseases.
Goizueta Institute @ Emory Brain Health
My heart goes out to Dale's family, friends, and colleagues. Like all of the others posting comments here, I am saddened to hear this news.
In the early days of Athena, there was a great but yet friendly competition between Athena, the Younkin lab, and the Selkoe labs as we collectively laid out the underpinnings of APP processing and support for the amyloid hypothesis. Dale in particular, though, found a way to always be approachable and open. He taught me that science, even in industry, could be fun, and that competition and constructive criticism was healthy.
Dale and colleagues' later work inspired me to jump on the immunotherapy bandwagon, and this area of research has been one of the mainstays of my research for over a decade. I think one day the larger scientific community will recognize that the dogma-breaking discovery—antibodies to treat brain disease—had a truly transformative effect.
It is so unfortunate that Dale did not live to see the day an immunotherapy was approved for treatment of a neurodegenerative disorder. I will miss his intellect, collegiality, and seemingly limitless enthusiasm and optimism. The AD field has lost one of our brothers.
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