Katie & Allie Buryk Research Fund
Supports research for Late Onset Tay-Sachs and Sandhoff (LOTSS) disease.
Fundraising Goal: $1,250,000

Ways to Give
NTSAD Research Initiative Grants supported by the Katie & Allie Buryk Research Fund
Late Onset GM2 Gangliosidoses Registry and Repository
Principal Investigator:
Florian S. Eichler, MD, Massachusetts General Hospital
This project aims to develop a both a clinical registry and a repository of samples for Late Onset GM2 Gangliosidoses. The registry will use the NeuroBANK platform to create and implement use of electronic case report forms, allowing standardized data to be collected from patients with LOTS. Review of current medical literature and surveys of patients will help determine which data to include in the registry in order to establish meaningful outcome measures. Prospective evaluations of patients will also be used to determine these optimal outcome measures, looking at change over time, patient value of measures, and variability among patients. Samples collected will be used to identify potential biomarkersA measurable substance in an organism whose presence is indicative of some phenomenon such as disease, infection, or environmental exposure. More of disease progression and to correlate these biomarkers with clinical outcomes. Both clinical outcome measures and biomarkers are essential components of clinical trial readiness, necessary to show effect of any experimental therapy.
Generation of a knock-in mutant Hexbmouse model
Principal Investigator:
Eric R. Sjoberg, PhD , OrPhi Therapeutics
This project supports the development of a mouse modelA laboratory mouse useful for medical research because it has specific characteristics that resemble a human disease or disorder. Strains of mice having natural mutations similar to human ones may serve as models of such conditions. Scientists can also create mouse models by transferring new genes into mice or by inactivating certain existing genes in them. Definition from: National Human Genome Research Institute (http://www.genome.gov/glossary.cfm) More for Late Onset Tay Sachs and Sandhoff diseases. Mice with Sandhoff disease are used to study both diseases because both store GM2 gangliosides and because mice with mutations in the HEXA gene which causes TSD do not develop features of TSD due to an alternate pathway for GM2 degradation. This model is different from currently existing SD mouse models in that it has a specific mutationA change in the sequence of DNA. Many mutations are "silent" and do not cause disease. When mutations occur in genes and disrupt the production of a functional protein, they may lead to genetic disease. More that leads to residual enzyme, as is seen in the late onset forms of these diseases in humans. This new model will be used to study pharmacological chaperones, small molecules that can bind and stabilize mutated enzyme. This allows the misfolded enzyme to reach the lysosome and degrade stored material correctly. The two chaperones that will be studied have been previously shown to increase both HexA and HexB enzyme in healthy mice. The project will look for increased enzyme activity and reduced gangliosideAny of a group of glycolipids that yield a hexose sugar on hydrolysis and are found especially in the plasma membrane of cells of the gray matter. Definition from: Merriam-Webster's Medical Dictionary http://www.m-w.com/ by Merriam-Webster Inc. More storage in the brain. The mouse model will also be made available for other late onset research.
Identifying Novel Therapeutics for Treating GM2 Gangliosidoses
Principal Investigator:
Beverly L Davidson, Ph.D., Children’s Hospital of Philadelphia (CHOP)
The drug Miglustat (approved for Gaucher disease in 2002) does not cross the blood-brain barrier to an extent that could mediate benefit in a clinical trial in patients with late onset Tay-Sachs disease. In this study, they are using a powerful drug discovery approach to identify FDA approved drugs that have improved brain penetrance while simultaneously share the same efficacy as Miglustat.
They have submitted 49 samples to the University of Iowa, Genomics division for high-throughput RNA-sequencing. These samples represent 7 donors treated with the three drug treatments and controls at two different doses.
Next Steps: They will query the LINCS database with the RNA-seq data, identify drugs and validate hits over the next 4-6 months. Importance: These important preliminary studies will help identify additional, brain penetrable drugs that may find use in substrateThe substance on which an enzyme acts. More reduction therapy for the gangliosidoses.
Clinically Relevant Outcome Measures for Patients with Late Onset Tay-Sachs disease Ascertained Real-Time Through Patient Wearable Technology
Principal Investigator:
Cynthia J. Tifft, MD, PhD, National Human Genome Research Institute, National Institutes of Health
This proposal is a next step in identifying relevant outcome measures for clinical trials. Considerable data on the late onset Tay-Sachs (LOTS) and Sandhoff (LOSD) patients has recently been collected at two sites (Massachusetts General Hospital and the NIH Clinical Center) as well as the last two NTSAD Annual Family Conferences and this exploratory study would expand the range of outcomes to metrics relevant to the daily lives of LOTS and LOSD adults, including their ability to move about and participate in the activities of daily living.
This is a 6 month exploratory study using 5-8 ambulatory or partially ambulatory adult patients with late onset Tay-Sachs or Sandhoff disease to collect patient data on ambulation, falls, and wake/sleep cycles and other patient input that can be tested as clinically relevant outcome measures for future clinical trials. Data is collected through a wearable device and transmitted through a mobile app to Dr. Tifft for analysis. The data collected will be compared to clinical testing including gait lab metrics to be conducted at the NIH Clinical Center at the time of initial evaluation and at the 6 month endpoint.
Accelerated program for CSF delivery of AAV gene therapy for Tay-Sachs and Sandhoff patients
Principal Investigator:
Miguel Sena-Esteves, PhD, University of Massachusetts Medical School
While intracranial injection of AAV vectors is the most advanced gene therapy for Tay-Sachs and Sandhoff diseases, the current approach involves two vectors encoding separately the hexosaminidase ATay-Sachs is caused by a mutation in the HEXA gene on chromosome 15. The HEXA gene codes for the alpha subunit of the hexosaminidase A enzyme which is necessary for breaking down GM2 gangliosides in nerve cells. When there is a mutation in the coding for alpha subunit of the hexosaminidase A it does not function properly and leads to an accumulation of GM2 which is toxic and eventually causes cell death. Sandhoff is characterized by loss of function of both the alpha and beta subunit of hexosaminidase A enzyme. For more information visit: http://ghr.nlm.nih.gov/gene=hexa More (HexA) alpha- and beta-subunits, which are injected bilaterally in the thalamus and one cerebral lateral ventricle. There are drawbacks to this approach, such as the invasiveness of direct injections into the brain that require a neurosurgical procedure, and its use of two AAV vectors which double the costs of manufacturing and an eventual treatment. After much initial work, there are now single AAV vectors carrying both subunits that show promising results in GM2 mice. These new vectors can enter the brain effectively after injection into the bloodstream, or injection into the cerebral spinal fluid (CSF). Presently it is unknown which approach will be the most effective and therefore it is important to test both.
To date, ongoing studies testing bloodstream delivery of these new AAV vectors in GM2 mice have shown very promising results. This project will focus on the delivery of AAV vectors to the central nervous systemThe central nervous system is that part of the nervous system that consists of the brain and spinal cord. The central nervous system (CNS) is one of the two major divisions of the nervous system. The other is the peripheral nervous system (PNS) which is outside the brain and spinal cord. The peripheral nervous system (PNS) connects the central nervous system (CNS) to sensory organs (such as the eye and ear), other organs of the body, muscles, blood vessels and glands. The peripheral nerves include cranial nerves, spinal nerves and roots, and what are called the autonomic nerves that are concerned specifically with the regulation of the heart muscle, the muscles in blood vessel walls, and glands. More through CSF administration (e.g. intrathecal space) which has several advantages to treat Late Onset patients. The funding will primarily support a research associate to conduct mouse studies related to CSF delivery of AAV9 vector in GM2 mice including generating mice, injections, behavioral studies, histological and biochemical analyses of tissues post-mortem.
Minimally invasive delivery of AAV gene therapy in the Tay-Sachs Sheep
Principal Investigator:
Heather Gray-Edwards, PhD, Scott-Ritchey Research Center, Auburn University, Auburn, AL
Goals of the Proposal
- To evaluate efficacy of adeno associated viral (AAV) gene therapy after cerebrospinal fluidThe fluid within the subarachnoid space, the central canal of the spinal cord, and the four ventricles of the brain. The fluid is formed continuously by the choroid plexus in the ventricles, and is reabsorbed into the blood by the arachnoid villi at approximately the same rate at which it is produced. More (CSF) delivery in the sheep model of Tay-Sachs disease (TSD)
- To confirm previously proposed biomarkers of TSD, including MRI image, lipidomic signatures, cognitive testing, and neurologic evaluation
- To study the biodistribution and clearance of CSF delivered AAV gene therapy in the Tay-Sachs sheep
Impact of Research
Gene therapy, is one of the most promising treatment options in development. The study will evaluate the efficacy and biodistribution of the state-of-the-art gene therapy in TSD sheep. Tay-Sachs sheep is one of the most relevant animal models of the disease, due to its large brain size and suitability for various biomarker studies.
The findings in this proposal will aid in expanding our knowledge on the treatment’s administration and biodistribution. The efficacy profile from the work with be necessary and helpful for future regulatory application before FDA. Most importantly, this study will generate useful data and insight about TSD biomarkers and contribute to future clinical studies in human patients.
Amendment to complete safety study in non-human primates
Principal Investigator:
Miguel Sena-Esteves, PhD, University of Massachusetts Medical School
Thank you from the bottom of our hearts for your support!
As of March 2, 2023, the fund has recieved 3,627 donations from 2,377 generous donors!
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Kevin Borgia |
Kymn Goldstein |
Kelly Hodges |
Kim Parham |
Kimberly Grabel |
Jean Kirch |
Susan Kahn |
Rachel Moore |
Kate Polles |
Katherine Marshall |
Claudia Kristensen |
Lorraine and Kevin Martinez |
Karen Lometti |
Karen Brewer |
Karen and Neil Farina |
Kathryn Hannon |
Kamran Moattar |
John Kosanke |
Kathleen Feeney |
Kristina Preisner |
Marci Kraft |
Neil Kraft |
Marilyn Yarmark |
Kristen Singagliese |
Kristi Draper |
Kristofer Velasquez |
Karen Mandel |
Scott Kunz |
Kurt DeMars |
Mike Kuzan |
Lisa Gavales |
Helen and Larry Rubin |
Laken Masterson |
Lance Primis |
Laura Eister |
Claire and John LaRosa |
Larry Pollack |
Michele Reisner |
Larry Leibowitz |
Laura Goldenberg |
Linda and Denny Urban |
Lauren Arcoleo |
Lauren Funke |
Lauren Rodriguez |
Laurena Emhoff |
Lauren Karp |
Ann Marie and James Hartnett |
Susan Garelick |
Helene Lax |
Raymond Lowe |
Lisa Ayoob |
Leonard Kaye |
Lorraine Stolove |
Linda Coppede |
Renee Dixon |
Lee Feldman |
Leona Kern |
Lee Schrager |
Leigh Diveris |
Lorren Elkins |
Lee and Bridget Russell |
Lila Brauer |
Lesley Heller |
Leslie Konigsberg Levy |
Howard Levine |
Ellen and Russell Lewis |
Louis Gazitano |
Larkin Glazebrook |
Louis Hafken |
Lucy Mele |
Leslie Hoenninger |
Lia DalCortivo |
Elizabeth and Liam Carlos |
Lida Devino |
Linda Gross |
Linda Fargo |
Linda Freedman |
Linda Alboher |
Linda Roberts |
Lisa Calabrisotto |
Lisa Basteiro |
Lisa Petriccione |
Karen List |
Elizabeth Casey |
Elizabeth Holland Weiss |
Elizabeth Shupak |
Elizabeth Connor |
Lainie Simon |
Lara Eisner |
Cherryl Llewellyn |
Lloyd Backus |
Larry Mark |
Louis Fabrizio |
Canyon Capital Corporation |
Linda Neumann |
Logan Pomeroy |
Lois Glassman |
Lori Heinl |
Lorraine Ferretti |
Patricia McAvoy |
Patricia McCarthy |
Louise Hornor |
Louis Naviasky |
Libby Panzer |
Lauren Resnick |
Linda and Ira Shoolman |
Linda Schwarz |
Len Margulies |
Linda Tondow |
Lydia Dufour |
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Lyndsay Suchy |
Lynn Klein |
Lynn Baldwin |
Lynne and Robert Buly |
Lynn Graf |
Elyssa Michaels |
Lorraine Pollak |
Makesha Hatten |
Timothy Maby |
Carmine Raimondi |
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Carol Magun |
Melissa Kirsch |
Maxine Andewelt |
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Marcia Cherry |
Marcy Smothers |
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Maria Arnone |
Maria Fields |
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Mark Blaifeder |
Mark Trifon |
Marla Goodman |
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Marshall Burak |
Marlene Grossman |
Marisela Arteaga |
Martha and Jerry Krasne |
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Martine Reardon |
Martin Zweifler |
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Dan Purjes |
Mary Durkin |
Mary Kay Liotta |
Mary Mule |
Mary Bustin |
Mary Ann Stein |
Matt Cooper |
Maxine Spector |
Maydan Rothblum |
Michael Berkowitz |
Elaine Horwitz |
Michael Cooper |
Rita Buress |
Marcia Chapman |
Aidan McNulty |
Patricia McSweeney |
Marla and Douglas Czumble |
Meagan McInerney |
Meagan Lech |
Emily Oseroff |
Meghan Natalicchio |
Meighan Meeker |
Meirelys Ruiz |
Melodie Jacques-Kunis |
Esther & Melvin Zirkes |
Meredith Kopit Levien |
Meredith Wells |
Mark & Elaine Faber |
Michael Fishman |
Richard H Miller |
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Michele Frankel |
Michael Arciprete |
Michael Buryk |
Michael Colucci |
Michael Greenspon |
Michael Traison |
Michael Carroll |
Michael Grissom |
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Michelle Kraemer |
Michael Oreskovich |
Robin Grove |
David Shifrin |
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Milton Klein |
Mindy Goldfischer |
Mitch Scherzer |
Manuela Paz |
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Michelle Gaines |
Mark Lisnow |
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Michael Markowitz |
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Megan Hess |
Martha Niessen |
Mollie Reisman |
Cynthia O’Reilly |
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Monte MacDiarmid |
Morgan DeAmicis |
Galicia Contracting and Restoration Corp. |
Marc Fishbein |
Mike Graczyk |
Mark Ricklis |
Marjorie Levin |
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Norman & Mary Rita Weissman |
Maria Sergi |
Melissa Cohen |
Michael Silverstein |
Malerie Simon |
Myisha Trice |
Tom Mulligan |
Goetz Middle School |
Sari Mundie |
Linda Bojman |
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Myrna Lewak |
Norman Abramson |
Nancy Lee |
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Neil Cohen |
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Neal Lucas |
Norman Parker |
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Nicole Mastrangelo |
Nicole Klee |
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Kate Sanderlin |
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Neiman Marcus |
Nicole Miller |
James Kerwin |
Anonymous |
Norma Loeb |
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Joseph Nulty |
Robert Nusspickel |
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Marion O’Grady |
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Jeff Yunis |
Kenneth Olshansky |
Norman Rapoport |
John O’toole |
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Pamela Gubitosi |
Paul Prince |
Pat McPeake |
Patricia Page |
Patti Wold |
Bonny and Paul Cohen |
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Compass Mining, Inc |
Rachelle Friedman |
Phyllis Calvano |
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Alan Gober |
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Paulette Albert |
Peter Berman |
Peter Michel |
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Philip Turner |
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Randy Kabat |
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Robert Din |
Robert Chavez |
Richard Knorr |
Ryan Drant |
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Remy De la Mauviniere |
Joe Septimus |
Rick Freeman |
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Rebecca Termotto Hayevy |
Rhoda Goldstein |
Richard Cacciato |
Brittany Richardson |
Richie Pecci |
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Richard Berke |
Gould Family Foundation |
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Lee Riffaterre |
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Rhonda Cole |
Rebecca McPheters |
Roanne Licht |
Robert Reif |
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Roe M. Powell |
Roland Caputo |
Lucia Diaz |
Joy Fallek |
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Steven Cohen |
Rosemary Bevacqua |
Richard Ross |
Francine Goldberg |
Richard Reibstein |
Ruth Reibstein |
Lauretta Prestera |
Robert Katz |
Richard Margolis |
Charles Valan |
Ruth Mazurek |
Catherine Murphy |
Stanley and Nancy Turetsky |
Sally Wasserman |
Auburn Jewelry LLC |
Sameer Dalamal |
Samantha List |
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Max Amper |
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Susan Telesmanic |
Sarah Kadis |
Sarah Morehead |
Saralee Rosenberg |
Sari Kadison-Shapiro |
Sasha Heroy |
Arlene Grand |
Wayne Sichel |
Stephen Kern |
Stewart Block |
Brenda and Solomon Watson |
Susan Schultz |
Susan Schultz-Geddes |
Daphne Schwab |
Sharon Kaiser |
Sheila Cole |
Anne Cameron |
Tommy Hilfiger |
Stefanie Paletz |
Savaria Drumm |
Patrick Sean Cassidy |
Irene Senter |
Macy’s |
Sue Kim |
Sharyn Barson |
Sharon Finch |
Sharyn and Larry Fradin |
Elizabeth Galiardo |
Stanley Fish |
Susan Macagnone |
Shari Kaplan |
Sharon Jolliffe |
Shawn Halleran |
Sheila Moran |
Shelly and Joe Mazzeo |
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Sherri Zigman |
Sherry Maher |
Andrena Bonte |
Robert Silverman |
Judith Itzkowitz |
Susan Luciani |
Susan Steinbreder Luciani |
Steph Jespersen |
Sharen Levine |
Stephanie Johnstone |
Steven Streen |
Steven Karash |
Susan and Jerry Hale |
Michael Scipione |
Susan Miles |
Sara Kosowsky |
Nancy Slavin |
Sarah Yu |
Stanley Lenkowsky |
Samantha Levine |
Solon Liberman |
Mariya Bugayenko |
Steven Bernstein |
San and Bob Miller |
Sheila and Dennis Smith |
Jeffrey Smith |
Stephanie Liotta |
Sandy Mervak |
Sherri Morr |
Paul Smurl |
Stephen Ochser |
Eileen Lewis |
Sarah Hogan |
Laura Sonnenfeld |
Sophie Brownlow |
Susan Peck |
Cindy Goldman |
Samantha Prusin |
Stuart Stoller |
Stuart Freedman |
Sandra Michaelson |
Suzanne & Robert Schaps |
Stephanie Gelber |
Stephanie Sharron |
Samuel Chodosh |
Stacey Block |
Stanley Runyon |
Susan Tarrence |
Stephanie Shnay |
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Steven Rappaport |
Stephen Hamburg |
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Steven Shapiro |
Stephen Shobin |
David Strome |
Sara Morgan |
Susan Brancati |
Sue and Don James |
Susan Loeser |
Barry Sufrin |
Margaret Heimbold |
Sonia Hudes |
Susan Silverman |
Susan Staub |
Susan Westlake |
Susan Ferber |
Susan Krimer |
Susan Green |
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Susan and Joel Landau |
Susan Weiner |
Susy Korb |
David Sutton |
Suzanne Kolen |
Stephanie Gasparro |
Sydney Liss |
Sharen Moghavem |
Shari Teitelbaum |
Tara House Jaffe |
Denine Taylor |
Tom Bodkin |
Tom DiCerbo |
Tom McDowell |
Lord & Taylor |
Terri Friedman |
Terry Oster |
Tressa Seetin |
SourceIndia, Inc. |
Todd Haskell |
E Baldwin |
Cindy Charney |
Renu Lonial |
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Seth Rogin |
Thomas Demarzo |
Elizabeth and Thomas Mela |
Megan Harris |
Timothy Lawrence |
Christina Kydoniefs |
Tina Vukov |
Tom Liotta |
Thomas Carley |
Janet Liotta |
Tracy Fudula |
Debora and Abe New |
Toby Chod |
Tom Helling |
Tom & Barbara Harper |
Anthony Giannini |
Gloria Shapiro |
Toby Fox |
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Trish Hall |
Trudy Burger |
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William Usnik |
Elaine and Martin Pasternack |
M Updyke |
Linda and Frank Urso |
Carlos Osmon |
Vanessa Willett |
Victoria Heslop |
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Victoria Miller |
Vinay Alessio |
Virginia and Michael French |
Vita Annitto |
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Victor Parada |
Vincent Sabio |
Valerie Salembier |
Valerie Weitzner |
Waleska Williams |
Brie Walsh |
Alex and Nancy Ward |
Warren Bimblick |
Wendy Baker |
William Buryk |
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William Abernathy |
Diane Wisniewski |
Brian Evans |
Willy Cepeda |
Lester Krasnogor |
Ellen Winetsky |
Susan Winter |
William DeMarzo |
Debbie and Bill Kahn |
Jessica Wolff |
William Pollak |
Andrew Wright |
Wylie Kain |
Anne and Richard Yagoda |
Yehuda Friedman |
Yasmin Namini |
Yolanda Casais |
Yolanda and David Marshall Reed |
Antony Young |
Yvonne and Barry Cohen |
Barbara Ribakove |
Elayna Zucker |
Sarita and Stanley Fish |