Ara Parseghian Medical Research Foundation

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Newsletter - A Goal for Life

December 2005

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The Newsletter of the
Ara Parseghian Medical Research Foundation
December 2005


Joy Beyond the Pain

The word Joy is often used around the holidays--in songs, on colorful greeting cards, even appearing as ornaments on a tree–and rightly so. Pain, on the other hand, isn't.

As this holiday season approaches, our hearts are filled with both of these conflicting emotions.

The pain, as you know, is from losing Marcia in August...and realizing three of our precious children are no longer with us. Words cannot describe this pain.

The you'll sense by the photo, comes from Ara's engagement to Cicely Ott of Tucson. Knowing we'll have a new daughter whom we dearly love brings us warmth and assurance about the future. Christa and Marcia knew Cicely as a loving "big sister." Ara will be blessed with a wife and lifelong partner who knows intimately the fabric of his family.

Joy also comes from having family and friends around the country who've held us up and carried us over this rocky path for the past eleven years. Thank you.

As well, we find joy in knowing there is hope for children living with NP-C. As a legacy to Michael, Marcia and Christa...and with all NP-C children and families in our hearts...our resolve is as strong as ever to be victorious over this disease.

Yes...Joy Beyond the Pain. The pain will never ever go away. With each new day, however, we move beyond as much as feel the joy around us.

We wish you a holiday season filled with the love of family and friends.

Mike, Cindy and Ara Parseghian

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The Caring McKennas

Patrick and Christine McKenna may not consider themselves extraordinary, but to the children and families touched by Niemann Pick Type C and other cholesterol metabolism disorders, the McKennas and others like them are truly heroic.

Patrick is the owner of Tempo Products, a company based in Solon, Ohio, which produces various fuel systems and accessories for marine after markets. He is also the former owner of Tempo’s parent company, PlastiKote. Patrick met Coach Ara Parseghian about 15 years ago in conjunction with publicity for PlastiKote and the men became fast friends. Over the years, the avid golfers have enjoyed many dinners and social events with their wives in Marco Island, Florida.

When Patrick and Christine, who are parents to five and grandparents to nine, heard the Parseghian children’s diagnosis of NP-C, Patrick said, “It was one of the worst things I ever heard of for a family to go through.”

A successful businessman himself, he is impressed and amazed at how Coach Ara and the Parseghian family rallied to form a foundation whose endeavor has snowballed into an international effort supported by 21 labs, hundreds of scientists, countless volunteers, thousands of donors and supporters.

From the Foundation¹s inception, Patrick said there was no question whatsoever that he and Christine would do what they could to help...a commitment that has resulted in numerous major donations to help find a cure for NP-C.

“We obviously think it is a wonderful cause and would do anything within our power to help secure the future for those battling this devastating illness,” Christine said.

This amazingly generous couple is representative of a strong base of Midwestern and Southern support that the Foundation feels fortunate to enjoy. There are many people throughout Indiana, Ohio, Illinois, Michigan and Florida to name a few, who quietly send donations, sponsor fundraisers and share their support and prayers with the APMRF on a regular basis.

Like the McKenna family, most of these people consider themselves “pretty pedestrian folks” who are moved to help make a difference. In Patrick McKenna’s words, “We are not heroes, but we try to do the best we can. Everyone who understands what’s going on has to pitch in.”

This holiday season, the APMRF sends a special wish for peace and joy to the McKennas and every other family who are helping each and every day to make the world a better and healthier place.

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Results of First NP-C Clinical Drug Trial

It is with great pride and hope that we share with our many donors and friends the interim results of the first NP-C clinical drug trial. After years of research, preparation and anticipation…this exciting milestone has been reached.

Our sincere thanks to you all for helping us fund Dr. Steven Walkley who performed the initial work with miglustat (Zavesca or OGT-918). Dr. Walkley of Albert Einstein College of Medicine administered this drug to NP-C mice with positive results. His study gave the green light for a clinical trial to move ahead.

The director of the trial in the US is Dr. Marc Patterson who has served on the APMRF’s Scientific Advisory Board since the inception of the Foundation.

The following excerpts are taken from a press release written by Actelion Ltd, which owns the rights to miglustat and is financing the clinical trial.

ALLSCHWIL, SWITZERLAND - 27 October 2005 - Actelion Ltd announced today a poster presentation at the annual conference of the American Society of Human Genetics of one-year results from a randomized controlled study evaluating safety and efficacy of miglustat (Zavesca®) in patients suffering from Niemann Pick Type C (NP-C), a rare genetic disease associated with multiple neurological manifestations.

The 29-patient-study showed trends toward improvement or stabilization in terms of saccadic eye movement, swallowing and audition in patients receiving miglustat compared to standard of care.

Marc Patterson, M.D., FRACP, Professor and Head, Division of Pediatric Neurology at Columbia University New York/USA, commented: “We know already that miglustat crosses the blood-brain barrier and accesses the brain. For the first time, we have been able to observe some potentially beneficial effects in patients with NP-C. I am also encouraged with these observations as they could suggest some restoration of function in neurons that have been altered by the disease process. As such, this study is another step forward in our quest to understand and potentially treat this complex disease”.

The study is being carried out at both Columbia University, New York and The Royal Manchester Children’s Hospital in the UK.

Results from the 12-month data showed improvement in horizontal saccadic eye movements and improvement in swallowing, none reaching formal statistical significance. The analysis also showed stabilization in auditory acuity in treated patients compared with deterioration in the untreated group.

Based on these results, the study will continue as planned for a further 12 months during which time all patients will receive miglustat and will be followed with the same set of assessments. A clinical trial with children in both the US and the UK is currently in progress as well.

NP-C researchers around the world are closely monitoring the results of these trials. Several of the scientists currently being funded by the APMRF are working on additional drugs, which if used in combination with OGT-918 may prove even more significant. The thought is that it will take a “cocktail” of drugs and therapies to treat NP-C.

The APMRF is committed to raising the funds needed to develop this combination so that we can save the lives of everyone afflicted with NP-C. Thank you for helping us with this vital and urgent goal.

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Potential Therapies for NP-C

Authors: Chatterjee S. and Dev K.K. Niemann-Pick Type C Disease, Scientific Conference Review. Investigational Drugs db (2005) Online Article RF633476.

The following is a report of selected highlights relating to potential therapies for NP-C from the 2005 Scientific Conference on Niemann-Pick Type C Disease sponsored by the APMRF.

The Ara Parseghian Medical Research Foundation (APMRF) is a private body that funds research into Niemann-Pick Type-C (NPC) disease. In order to bring the NPC community together and exchange data and ideas, the APMRF organizes a scientific research conference each year in Tucson, Arizona. This year the conference was attended by about 75 researchers. The following is a brief summary of advances in potential therapies for NP-C disease.

1. Allopregnanolone and Ganaxolone
Cholesterol is required for maintaining the structural integrity of membranes. In addition, cholesterol is also metabolized to produce hormones and steroids. Xun Huang and Matthew Scott (Stanford University) spoke about NPC1 dysfunction in the fruit fly, Drosophila. Mutations in Drosophila NPC1 result in cholesterol accumulation and larval lethality. Xun Huang showed that NPC1 mutant lethality can be rescued by feeding the flies with either cholesterol, 7-dehydrohydroxy cholesterol or ecdysone, a cholesterol derivative.

Allopregnanolone, another cholesterol derivative, is a neurosteroid and is required by neurons for proper growth and function. In NPC patients, the levels of Allo are reduced.

In an elegant study, the group of Synthia Mellon (University of California, San Francisco) has shown that a single administration of Allo at an early stage prolonged the average life span of NPC mice from 67 days to 124 days. Although promising, Allo is quickly metabolized and hence not suitable for clinical trials.

Of interest, Ganaxolone (Marinus Pharmaceuticals), is a stable form of Allo and is currently being used in a clinical trial to treat epilepsy in children. Ganaxolone is also presently being prepared for a clinical trial in NPC disease (William Pavan and Forbes Porter, NIH). It is hoped that clinical trials can begin once outcome measures have been identified.

The above studies show that defects caused by lack of NPC1 can be rescued by cholesterol derivatives in fruit flies, mice and man.

2. Zavesca/OGT-918
In addition to a deregulation in cholesterol storage, NPC patients also suffer from the accumulation of gangliosides and glycosphingolipids (GSL). Steve Walkley (Albert Einstein College of Medicine) presented evidence showing that double mutant mice lacking NPC1 or NPC2 and GalNAc-transferase (an enzyme in the GSL synthetic pathway) showed a lower cholesterol accumulation phenotype. His studies indicate a link between NPC1/NPC2 and the GSL recycling pathway. In this regard, there is an ongoing clinical trial using ZavescaTM/OGT-918 (Actelion Pharmaceuticals Inc,) supervised by Marc Patterson, Columbia University.

Interim analysis of first year data from the adult trial conducted in both the US and the UK is available on Actelion’s website at (click on Media, then Media Releases). This compound has already been shown to be effective in prolonging the lifespan of NPC deficient mice from 67 to 87 days (Steven Walkley, Albert Einstein College of Medicine).

3. LXR agonist T0901317
Daniel Ory (Washington University School of Medicine) spoke about the use of the Liver X Receptor (LXR) agonist T0901317 as a possible treatment for NPC disease. T0901317 is a synthetic LXR ligand and treatment of NPC mice with this compound (at 18 days) delayed the onset of neurological symptoms by two weeks. Moreover, a combination therapy of this drug along with Allo blunted the decline in cerebellar function further and increased lifespan by 72%.

The use of LXR agonists could thus prove valuable in treating NPC disease.

Steven Walkley also showed that compounds inhibiting the constitutive active androsteron receptors (CAR), could induce the NPC cellular phenotype. CARs have been implicated in NPC disease and they belong to the family of nuclear orphan receptors, similar to LXR. Taken together, these studies show that modulation of nuclear orphan receptors could play a role in NPC disease.

4. Compound Screens, Micro-array Analysis and HTS Gene Screens
In an effort to identify compounds that reduce cholesterol accumulation in NPC cells, Fred Maxfield (Cornell University) presented work done on developing a high content compound screen. His lab has set up an automated screening and imaging facility to monitor intracellular cholesterol accumulation in response to compounds.

The identification of new genetic targets for NPC disease was presented by two groups. First, Suzanne Pfeffer (Stanford University) presented micro-array data obtained by comparing gene expression profiles of wild-type and NPC1 mutant fibroblasts. This data has revealed several genes that are differentially regulated in NPC1 mutant cells, some of which are currently under further investigation.

Sandipan Chatterjee and Kumlesh Dev (Novartis Pharma AG) gave an overview of the project to identify novel genes involved in intracellular cholesterol trafficking and NPC disease. Using a cell based luciferase assay, a high throughput overexpression screen will be preformed to look for modifiers of cholesterol movement within the cell. The idea is to identify genes that modulate intracellular cholesterol accumulation and promote cell survival.

Drs. Chatterjee and Dev and researchers mentioned in this review are funded by the APMRF.

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Heartfelt Thanks...

We are so appreciative of the many events and projects held across the country in support of the APMRF in our battle against NP-C disease. Every dollar raised brings us closer to finding a treatment and cure. Following are a few of the events that have taken place over the past several months:

There’s a special little fellow in Cincinnati, Ohio by the name of Casey Kahl. Each year his parents, Jim and Karen Kahl, along with his grandparents, Dr. and Mrs. James Kahl, and a wonderful group of caring friends host an annual fundraising event called “Swing for a Cure.” This year’s golf event, the fourth annual, was a great success. Our sincere thanks to the Kahls and everyone from Cincinnati for working to save the life of Casey and all children living with NP-C.

Members of the Notre Dame Club of Milwaukee have great fun at their annual “Ara’s Outing” to benefit the APMRF. More importantly, they rally behind Coach Ara who is the honored guest each year in helping to fight NP-C disease. Hats off to all of the organizing committee members and participants whose generosity nearly doubled last year’s proceeds. This ND Club in Milwaukee is a shining example of the support the Notre Dame family across the US has shown since the inception of the Foundation.

Vince and Josephine Tenuto have hearts as big as Lake Michigan. Each year they organize and host the Ara Parseghian Charity Golf Day in suburban Chicago. This year’s event, the 6th annual, was held at Gleneagles Country Club in Lemont, IL on August 19, 2005. Upon hearing the news of Marcia Parseghian’s death shortly before the event, Vince called to express sympathy to Cindy and Mike…and to say they were already looking ahead to next year’s event in memory of Marcia and in dedication to all children and families living with NP-C disease. Thank you Vince.

“Go Irish!” This chant could be heard loud and clear at the Notre Dame vs. USC football game tent party on October 15, 2005. More than 120 guests enjoyed this pre-game gathering hosted by Joe Donovan, a ND alumnus and personal friend of Cindy and Mike Parseghian, and his company Credit Suisse First Boston. Coach Ara signed many autographs and the mood was festive. Fifty of the tickets were auctioned at events around the country to support NP-C research.

Written in a pretty pink heart on the front of the Leoni Family Event invitation this year was the word “Persevere”. Inside was a picture of their precious daughter, Jessica, and an invitation to their annual benefit held in Long Beach, CA on October 1, 2005.

The following special message was also included:

“Dear Friends, Since Memorial Day Weekend, Jessica has endured seizures that have greatly affected her health. The onset of seizures has heightened the sense of urgency we have always felt to find a cure.

Our theme ‘Persevere’ is especially appropriate at this time because we have tried to look to the future with a sense of hope and optimism. Our strength to persevere comes from the blessings of your prayers and the support you share with us.

To each of you, we extend our heartfelt thanks. With your help, we can keep the sparkle in Jessica’s eyes. The Leoni Family”

Drawing from the love and support of event co-chairs Bob and Patty Fisher and a host of other family members and friends who volunteered, the Leoni’s celebrated the life of Jessica and all children with NP-C while raising much-needed funds for research.

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Those Who Care ...Tucson's Dave Sitton

Dave Sitton is perhaps one of the most well-known and well-respected Tucsonans you will ever find. Not only is he the General Manager of Tucson’s Clear Channel Outdoor which is a very full-time job, Dave is the U of A’s Rugby Coach and is the “Voice of the Arizona Wildcats” for basketball games.

It’s hard to believe he has spare time—but Dave also serves as a volunteer emcee at numerous local charity events including our annual “One More Victory, Ara!” Celebrity Gala where Dave has charmed and entertained guests for many years.

"I met Mike and Cindy before we all had kids. They have always held a special place in my heart. Then Marcia and our daughter, Olivia, were in preschool together. We reestablished our friendship when NP-C came into our lives…all our lives.”

Sue Brooks, a local businesswoman and community volunteer, approached Dave this past summer about a fundraising project to sell lime green wristbands in honor of Dave’s recent battle with lymphoma. In the heart of his chemotherapy sessions, Dave consented and more than $27,000 was raised in a short time to benefit lymphoma research as well as other causes dear to Dave’s heart.

Among those charities was the APMRF to which he donated $5,000. “Of all the things I raise funds for worldwide, I don’t know of anything more worthwhile than the mission of the Ara Parseghian Medical Research Foundation.”

Thanks, Dave. You are a remarkable person.

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© 2008 Ara Parseghian Medical Research Foundation
3530 E. Campo Abierto, Suite 105, Tucson, Arizona 85718-3327, Phone: (520) 577-5106 Fax: (520) 577-5212, E-Mail: