hopelines October /11SAVE THE DATE…

Inside: 2/ Letter from the Board President 4 - 5/ Faces of Hope 6/ Reception and Lab Tour 7/ High Heel Fun Run Hikes Hope - continued

Grammy-Award winning vocalist Steve Tyrell will perform at the 8th Annual Evening of Hope.

Please save the date for the 8th Annual Evening of Hope to be held on Thursday, April 26, 2012 at the Sheldon Concert Hall. The evening begins with cocktails, dinner and the concert followed by a dessert reception with the artist.

The Evening of Hope will feature a performance by Grammy-winning vocalist Steve Tyrell, who reinvented and re-popularized classic pop standards for a modern-day audience. With the grit and soul of a lifetime of experiences, producing hits for Grammy-winning Artists ranging from Linda Ronstadt and Aaron Neville, to Rod Stewart and Diana Ross, Steve has sold hundreds of thousands of albums and gained a passionate following all over the world.

With sold out shows across America and raves from around the world, his following increases day by day. Although Steve tours mainly with his band, he also enjoys playing with some of the most renowned orchestras in the land. At the request of the Sinatra family and Quincy Jones, Steve was the featured performer with the Hollywood Bowl Orchestra at their season opening concert in which Frank Sinatra was inducted into the Hollywood Bowl Hall of Fame. Also at the request of the Sinatra family, he reprised that performance this past May at Carnegie Hall. This is one of the rare times the family has reached into the vault of original Sinatra arrangements to share them with another artist.

Steve’s work in the studio as a record producer has included collaborations with many diverse and legendary artists. In addition to the previously mentioned artists, Steve has worked closely with Ray Charles, Smokey Robinson, Mary J Blige, Blood Sweat and Tears, Chris Botti, Dave Koz, Dolly Parton, Bonnie Raitt, Burt Bacharach, Bette Midler, and Stevie Wonder.

His songs have been recorded by such revered artists as Ray Charles, Diana Ross, LL Cool J and Elvis Presley. Aside from being a Grammy Award winner, Tyrell has earned two Emmy nominations, 3 Ace Nominations, the 2004 American Society of Young Musicians “All That Jazz Award”, the 2004 Wellness Community’s “Human Spirit Award”, the 2006 Society of Singers “Lifetime Achievement Award”, and the 2008 Los Angeles Jazz Society’s “Jazz Vocalist of the Year”.

For further information, visit Steve Tyrell’s website: www.stevetyrell.com

The 8th Annual Evening of Hope – April 26, 2012

Ticket and Sponsorship InformationTickets for this enchanting musical evening are $250 per person. Sponsorships are available at various levels, beginning with Patrons at $1,000 per couple up to Principal Sponsors at $20,000 and over. If you were a sponsor or patron for last year’s Annual Evening of Hope, we thank you for your generous support and look forward to your continued support for the 8th Annual Evening of Hope.

In order to reach our goal and allocate necessary funding to the Hope Center for Neurological Disorders at Washington University School of Medicine, we need your participation once again. The Hope Center continues to make significant progress in many important areas that affect the brain and nervous system. Proceeds from the 8th Annual Evening of Hope will support this collaborative and translational research – which one day will lead to cures that afflict thousands of people who are diagnosed with a neurological disorder every day.

We will soon be sending out sponsorship information with various levels of giving. If you or your company would like to become a new sponsor, please contact Bob Kindle, Executive Director, at (314) 725-3888 or e-mail at bob@hopehap bob@hopehappens.org.

A tribute to Christopher W. Hobler and Hans Vonk, former conductor of the St. Louis Symphony

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A Message from the Board President

All of the Hope Happens family wants to thank our donors for making 2011 an outstanding year. You made the 7th Evening of Hope the most successful ever, and your response to our inaugural “Hike4Hope Happens” exceeded expectations for a first-time event. We genuinely appreciate your friendship and involvement.

Your ongoing support allows the cutting-edge research taking place at The Hope Center for Neurological Disorders to continue in earnest. The focused approach by our team of world-class scientists and researchers will bring solutions to all these neurodegenerative diseases.

However, our most exciting news comes from the Hope Center. Last year, Dr. Tim Miller received authorization to begin Phase 1 trials on an antisense drug for patients with familial ALS. Dr. Miller and his team are the first to be allowed to administer this type of antisense inhibitor directly into the central nervous system. This trial has been designed to assess the safety and tolerability of the procedure in those patients having familial ALS.

This advancement exemplifies the concept and the philosophy of Hope Happens and The Hope Center. Using collaborative, translational research will bring treatments and cures more rapidly from bench to bedside giving hope to those currently afflicted, as well as to future generations.

With such exciting news, we look forward to an extraordinary year in 2012. Chris Hobler noted, there had been no advancements in the treatment of ALS in years. His dream, the Hope Center for Neurological Disorders, has resulted in a trial to challenge one of these horrific diseases. However, continued success and knowledge requires your assistance.

To accelerate these findings, Hope Happens helps fund innovative pilot projects. Hope Center faculty may request funds for two-year projects, which must be a collaboration among at least two laboratories, focus on fundamental mechanisms of neurodegeneration, and be “translational”, i.e., have the potential for therapeutics development. Up to four projects are awarded each year.

Our challenge for this upcoming year is to carry on the momentum generated by all this positive activity. All of us will share in the progress of The Hope Center and its people. At any moment, our dedicated team of scientists and researchers may discover the answer to a neurological disorder, which will then lead them to another, then another. Your support remains critical to bring hope to so many.

Sincerely,

Toby MartinBoard President

Our BoardHope HappensBoard of DirectorsToby Martin, PresidentDr. Thomas A. Woolsey, Vice PresidentWilliam Hizar, TreasurerChristopher Danforth, SecretaryMary BettisA.J. ChivettaLeigh Hobler GerardWilliam FinnieJean HoblerPeter HoblerJulie L. KindleCynthia MeinersMarcia MellitzThomas RuwitchClark ThomasSteve Wolff Hope HappensBoard of AdvisorsJohn BrightmanRussell BrightmanLou ChiodiniTony ChiodiniAimee DavisPete GenoveseJeff HerculesJen HoblerDavid Holtzman, MDHal KroegerFlip MaritzTim Philpott, MDCarole Wilson

Staff Robert E. Kindle, Executive Director

Gabriela Inderwies, Development Officer

The Hope Center for Neurological Disorders at Washington UniversityDirectorAlison Goate, DPhil

Executive DirectorAnneliese Schaefer, PhD

Executive CommitteeFloyd E. Bloom, MDJean HoblerDavid Holtzman, MDThomas R. MartinMarcia Mellitz, MBAThomas A. Woolsey, MD

Clark D. ThomasClark Thomas, Vice President of Stifel Bank & Trust, recently became a member of our Board of Directors. Clark’s interest and involvement in ALS Hope and Hope Happens stems from a special childhood friendship. He and Chris Hobler attended John Burroughs School together. His lifelong friendship with Chris and relationship with the Hobler family has underscored his dedication and commitment to our cause.

After attending Vanderbilt University for undergraduate studies, Clark obtained his M.B.A. from DePaul Graduate School of Business. He took a position with Ralston Purina in Promotions and Marketing. From there he went to Midwest BankCentre where he was a Vice President and Loan Officer. Including his present employment at Stifel Bank & Trust, Clark has been in the mortgage lending world for 11 years.

Clark is married and has 2 daughters. His wife, Michele, whom he met while at Vanderbilt, is employed by Nestle Purina in Market Research. Keeping with family tradition, both children attend John Burroughs School. Cameron is a high school senior and Elise is a 9th grader.

In his spare time Clark is an avid golfer, as well as the Director of the Western Golf Association, which sends caddies to college through the Evans Scholar Foundation. He also enjoys photographing his kids’ sporting events.

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Stephen I. WolffFor the past 24 years, Steve Wolff has been actively engaged in real estate investment and management as the principal of Wolff Properties, a St. Louis-based firm that owns apartment communities, neighborhood shopping and convenience centers, suburban office buildings and single tenant net-leased properties. Prior to joining Wolff Properties, Steve was employed as an attorney at Greenebaum, Doll & McDonald in Louisville Kentucky. He specialized in banking and securities law.

Steve volunteers his time and expertise as a business leader to a number of organizations. Steve is a member of the American Bar Association, Kentucky Bar Association, the local and national chapters of the National Apartment Association, Urban Land Institute, and International Council of Shopping Centers. Steve earned a Bachelor of Arts degree from Duke University and a Masters in Business Administration and Juris Doctor from Washington University in St. Louis. In his personal time, Steve enjoys time with his wife, son and daughter, and is actively involved in numerous charitable and civic organizations.

Hope Happens Welcomes Two New Board Members

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Faces of Hope: David Holtzman, MD

Gabriela Inderwies interviewed Dr. David Holtzman, chair of the Department of Neurology at Washington University School of Medicine, and member of the Hope Center for Neurological Disorders’ Executive Committee. Dr. Holtzman’s areas of specialty include Alzheimer’s disease and neonatal brain injury.

Please tell our readers about your career at Washington University

I am a native St. Louisan but I moved away after high school. I was in Chicago for 6 years and in San Francisco for 10 years. My internship, residency, as well as all of my research training was at the University of California in San Francisco. I returned to St. Louis 17 years ago in 1994. At Washington University I continue to see patients, teach, and do research. I have always spent approximately 80 percent of my time doing research and 20 percent doing clinical work until the time when I became chair of the Department of Neurology. Although my duties now include administrative work for the university and Department of Neurology, I still spend at least half my time doing medical research.

Can you talk about the inception of the Hope Center?

I got to know ALS patient Jack Orchard. In a meeting I had with him in 2003, after becoming Chair of the Department of Neurology, we discussed some of the goals I had for both the department and for research in the area of neurological disorders. It was then Jack suggested I meet Chris Hobler. In a series of meetings I got to know Chris and the Hobler family and together with Mark Goldberg we crafted a vision for the Hope Center. Our vision was built on very similar overall goals focusing on the development of a center that studies neurodegeneration. Although there were some administrative stumbling blocks, we always thought that we would have the most success if groups of doctors, scientists, and researchers could collaborate together interact with each other. We wanted the ability to share ideas and advancements, with the ultimate goal of developing treatments and cures. I believe that there are many similarities in the pathways that eventually can lead to different neurological disorders. While many of the neurological diseases are different clinically, they also share

underlying similarities. With everybody united behind the vision of collaboration, we have made the Hope Center a success.

Please explain the urgent need for treatments and cures

If you think about medicine and human health in general, many of the diseases of man, like cardio-vascular disease or cancer, have seen major advances. Currently, in developed countries such as in the US, Europe, Japan, and Australia, the average lifespan is in the eighties. But virtually all neurodegenerative disorders increase with aging. With the exception of the fact that the incidence of stroke is diminished because of treatment of cardio-vascular risk-factors, the incidence rate of most of the other neurological disorders has not decreased. I think in all of medicine, neurological disorders are probably the biggest threat to our society. Just look at Alzheimer’s and Parkinson’s disease. The incidence rates of these debilitating illnesses are increasing in numbers because people are living longer. Furthermore, there is no single treatment for most of these diseases that delays their onset. But there is reason to be hopeful because some treatments have had positive impact. In MS for example some of the new treatments are very beneficial for patients. We should be confident that we really can develop therapies. It just requires more research and more devotion from many sources. Not only do individual donors need to step up, but the government does as well. There needs to be an ongoing source of funding, especially for new, innovative projects. In the last five years, the government funding has been tighter than ever, especially with the economic downturn. The amount of funding that goes to neurological diseases compared to, for example, cancer or HIV is disproportionately low, given that there are few therapies for neurological diseases. We have to increase research spending on all the neurological disorders and look at all the funding sources together, both private and government, in order to move forward.

Can you describe some of the scientific breakthroughs made at the Hope Center?

There have been many breakthroughs at the Hope Center. I find it is difficult to select just a few and I cannot highlight all of them. But one important breakthrough is the discovery of the first mutation in the

David Holtzman, MDDr. David Holtzman attended the

Honors Program in Medical Education

at Northwestern University receiving his

B.S. (1983) and M.D. (1985). He did a

medical internship followed by a Neurology

residency at UCSF from 1985-1989. He

then did post-doctoral research training in

the lab of William C. Mobley, M.D. , Ph.D.

at UCSF from 1989-1994. While at UCSF,

he established the Memory and Cognitive

Disorders Clinic and was an Assistant

Professor from 1991-1994. In December

1994, he moved to his own laboratory at

Washington University. He was named

an Associate Professor of Neurology in

2001, a Professor in November 2002, the

Andrew and Gretchen Jones Professor, and

the head of the Department of Neurology in

October 2003. In additional to his laboratory,

administrative, and teaching duties, Dr.

Holtzman is involved in clinical and research

activities at the Washington University

Alzheimer’s Disease Research Center. Past

honors include being the recipient of both

a Paul Beeson Physician Faculty Scholar

Award in Aging Research and the 2003

Potamkin Prize from the American Academy

of Neurology for research on Alzheimer’s.

Additionally, he was elected to the American

Society for Clinical Investigation (2004),

received a MERIT award from the NIA

(2004), received the MetLife Award on

Alzheimer’s disease (2006), as well as being

elected to the Institute of Medicine of the

National Academy of Sciences in 2008.

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gene TDP-43 by Drs. Nigel Cairns, Bob Baloh and Alison Goate. They discovered a mutation in a gene that causes ALS. Since that breakthrough the whole research community has worked very hard trying to develop animal models of this gene mutation to develop therapies, and the first good model of the TDP-43 related ALS was developed by Dr. Baloh’s lab here in the Hope Center. Do we have a treatment yet? No. But at least we have more models in animals that could ultimately be useful in developing new therapies for people.

Another breakthrough comes from Hope Center scientist Dr. Randy Bateman, who developed a new methodology to test treatments for different neurological disorders. It’s a technique called SILK (Stable Isotope Labeling Kinetics). This is a major advancement and this technique is already used in humans to test efficacy of treatments in development.

I also want to mention Dr. David Brody and Dr. Christine MacDonald’s work on traumatic brain injury as another great example of a scientific breakthrough at the Hope Center. They showed for the first time that subtle injury can occur in military personnel exposed to blast injury. Early detection is important for all neurological disorders. This new MRI based technology allows the identification of people who you would not necessarily suspect to have an injury. It is important to note that this technology is also applicable for those head injuries sustained from sports and other accidents.

What is your own research focus?

I have two areas of interest. Most of my laboratory focuses on Alzheimer’s disease, but I have a longstanding focus on neonatal brain injury, as well.

I have been working on several different aspects related to Alzheimer’s disease since coming to Washington University. I am trying to understand why a gene called apoE is one of the major risk factors in

Alzheimer’s disease. Through a series of studies over several years we have been able to show that apoE4 is a risk factor and apoE2 is protective. We were also able to show that the apoE protein alters the clearance and aggregation of the amyloid beta protein in the brain. With this knowledge, our work is now focused on trying to sort out whether or not there are ways of enhancing clearance of amyloid via apoE and if this is a drug targetable mechanism.

Another major area of research here involves a therapy being tested in humans called active and passive immunization. People are either being actively immunized with amyloid-beta or they have been directly administered antibodies that target amyloid beta. We were able to show the possibility that this treatment may be useful to treat Alzheimer’s disease based on studies we carried out in mice. One of the antibodies we started working

on twelve years ago is now in a phase three clinical trial and currently being tested in humans by a drug company. In approximately one year the results from the trial will be available. We all hope that this or a similar treatment will be a useful treatment for Alzheimer’s disease.

Bio-markers are a third area in which we are focusing. The question here is whether you could develop markers for a disease and detect

the neurodegenerative disease occurring in people before they become clinically impaired. Right now, the best bio-markers that have been validated are brain imaging markers and cerebral spinal fluid markers. There are some leads that blood markers could also be useful. I hope that this can be validated as it would be much easier to apply.

The final thing in Alzheimer’s disease we have been working on is the connection between neuronal activities in the brain and why the regions in the brain that develop Alzheimer’s-related changes, tend to be those regions that are most active when people are cognitively not engaged in a specific task. We have been working very hard to understand this relationship, and it has been very fruitful. It might suggest why, in some of

our animal studies, having too little sleep might accelerate the onset of Alzheimer’s disease changes, or why certain lifestyles like exercising regularly might be helpful.

In terms of neonatal brain injury, relevant for cerebral palsy, we have been using an animal model where we investigate ways to protect the brain. Many children who develop cerebral palsy have injuries to the brain caused by hypoxia-ischemia.

Some of the agents we use in our research include substances with drug-like characteristics and others contain substances present in certain foods. There are some natural products that are very rich in poly-phenols, and they appear to protect the neonatal brain against this type of injury. More recently we have been working on a brain signaling cascade with Dr. Jeff Millbrandt that appears to be very protective to the neonatal brain.

What will be next in your own work?

We are still working on the gene apoE, trying to understand if we can develop a treatment based on it. It is by far the strongest genetic risk for Alzheimer’s disease, and now we know more about its biology and are in a position to develop therapies based on that knowledge.

We are also working hard on the relationship of sleep, synaptic activity, and Alzheimer’s disease. Those are two big areas of future research.

What are your final thoughts?

I would like to tell our readers that the model we created with the Hope Center really is working, and I hope that we can continue to have this model for a long time. Our environment is unique. I have traveled around the world to different places. Never have I seen a setup that utilizes the mixture of collaborative and investigative talent that we have at the Hope Center. There are good scientists and good ideas at other universities, and there is also some collaboration, but at the Hope Center we put them all together in a really beneficial and forward thinking manner. I hear all the time about scientists who are making inquiries wanting to come here, because they know that the Hope Center is a great place to work. This is wonderful and really exciting. This gives me all the reason to believe that we can ultimately develop treatments and cures for neurological diseases.

Thank you very much for your time!

“We should be confident that we really can develop therapies. It just requires more

research and more devotion from

many sources.”

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On September 13, 2011, our guests had the opportunity to listen to a lecture given by scientists and past Pilot Grant recipients, Dr. Tim Miller and Dr. Chris Weihl, and tour their laboratories. The informative lecture offered many opportunities for questions and culminated in an engaged dialogue between the scientists and Hope Happens’ constituents.

Dr. Miller and Dr. Weihl talked about their most recent work and the importance of continuous science funding, especially for experimental, innovative research projects such as Pilot Projects. Both scientists also emphasized how the Hope Center’s model of translational research is instrumental for making basic medical science discoveries.

Dr. Tim Miller, one of the nation’s foremost researchers on ALS, is the first director of the Christopher Wells Hobler Laboratory for ALS Research. Recently Dr. Miller expanded his laboratory space and added four new staff members.

Dr. Chris Weihl, Principal Investigator of the Weihl Lab, studies the fundamental pathological defects in neuromuscular disorders, such as muscular dystrophy, with a goal to identify therapies that will correct it in patients. In addition Dr. Weihl treats patients with neuromuscular disorders in the Washington University Comprehensive Neuromuscular Clinic.

Hope Center Reception and Lab Tour

Michael Houlihan (l.) and George Fonyo (r.) with Dr. Chris Weihl.

Dr. Chris Weihl explaining the process of protein folding to our guests.

Dr. Tim Miller, director of the Christopher Hobler Lab for ALS research, with Jean Hobler.

The inaugural Hike 4 Hope Happens took place on September 24, 2011 at Creve Coeur Lake Memorial Park. On a beautiful sunny day, participants gathered at the Tremayne Shelter to watch St. Louis’ first High Heel Fun Run, and then chose between a one or two mile Hike around the lake. St. Louis TV personality Heidi Glaus emceed the event.

Hope Happens’ founder and board member Jean Hobler was honored by County Executive Charlie Dooley for her outstanding contributions on behalf of people who are affected by neurological diseases, and September 24 was proclaimed Jean Hobler Day in St. Louis County.

The Hike 4 Hope Happens was not only a fun community event, but also offered lots of opportunities to learn about the urgent need for treatments and cures for all neurodegenerative disorders. All proceeds of the event go to the Hope Center for Neurological Disorders at Washington University School of Medicine and will be used to fast-track collaborative, translational research to find treatments and cures.

High Heel Fun Run Hikes Hope

In Memory of Grandpa DeLariaAndrew Miller

In Memory of Tom HerculesSteve CrainJerry DiSalvoDennis and Karen DoerrMary Grace HerculesWilliam and Janet LinhoffThomas and Marie Trost

In Memory of Chris HoblerJean Hobler

In Memory of Bill HuizingaRichard Huizinga

In Memory of John KindleBob and Julie KindleAlbert and Nancy Rose

In Memory of James MaritzJean Hobler

In Memory of Theodore MartinToby Martin

In Memory of Lillian “Pete” O’BrienShelly Weible

In Memory of Craig ReiterKevin and Janie Morrell

Hope Happens received a tremendous amount of support from the St. Louis community to make this very special event possible, and we would like to thank all our friends and sponsors who helped making the first Hike 4 Hope Happens a huge success.

Memorial Hike contributions were made in the names of

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Chris Danforth helps his son to get ready for the Hike.

Erin Armstrong, lucky winner of the bike donated by Big Shark Bicycle Company

Jean Hobler with son Peter Hobler, and granddaughter Allie Hobler.

Carolyn Kindle and Lucy enjoying the sun.

Hike participants at the opening ceremony.

Committee Chair Julie Kindle with St. Louis County Executive Charlie Dooley.

Hike 4 Hope Happens - continued

101 S. Hanley, Ste. 1320St. Louis, MO 63105

RETURN SERvicE REqUESTEd

Non-Profit Org.U.S. Postage

PAid St. Louis, MO

Permit No. 5653

OUR MISSION

At Hope Happens our mission is to improve the lives of people with neurodegenerative disorders by funding collaborative, translational research that has the potential to fast-track new treatments and cures.

How You Can Help Hope Happens

You can help shape the future of devastating neurological disorders

by donating to Hope Happens. Your generous donations will allow

doctors and scientists to do the research necessary to find cures

for neurological disorders such as ALS, Alzheimer’s, multiple

sclerosis, Parkinson’s disease, Huntington’s disease, epilepsy,

brain and spinal cord injury and stroke. We hope you will become

a member of the Hope Society, our annual giving program with

levels beginning at $1,000. Please see the envelope inside for

details or contact Hope Happens for more information.

Your donation can make a difference.

Bob Kindle

Executive Director

Hope Happens for Neurological Disorders

101 South Hanley Road · Suite 1320 · Clayton, MO 63105

314.725.3888

bob@hopehappens.org · www.hopehappens.org

The $10 Million Challenge supports the most promising basic and clinical research in neurological disorders. Your support furthers these programs to understand the causes of disease, develop improved treatments and search for lifesaving cures. Only through significant private funding will rapid advances occur.

Your gift to The Hope Center will:n Fuel the momentum on

fast-breaking research developments by eliminating the lag time in traditional funding mechanisms

n Fund exciting early-stage research too preliminary for government grants

n Support evaluation of new drugs and

therapies not ready for pharmaceutical company development

n Provide funding for targeted interdisciplinary research projects

For more information, please contact:Bob Kindle, Executive Director

You, too,can offerHOPE

The Danforth FoundationChallenge for The Hope Centerfor Neurological Disorders