PRF By The Numbers - Progeria Research Foundation

PRF By The Numbers

Produced by Leslie B. Gordon, MD, PhD; Medical Director

Please Do Not Reproduce Children’s Photographs Without Express Permission From PRF March 31, 2021

Introduction and Collaborations 3 – 10

Overview Data 11 - 20

International Progeria Registry 21 - 24

PRF Diagnostics Program 25 - 28

PRF Cell & Tissue Bank 29 - 38

PRF Medical & Research Database 39 - 43

Weighing – In Program 44 - 47

Clinical Trials 48 - 56

PRF Grants Program 57 - 62

Scientific Meetings and Workshops 63 - 66

Publications 67 - 69

© 2021 The Progeria Research Foundation. All Rights Reserved. As of March 31, 2021

Table of Contents

PRF By The Numbers is a data sharing tool originating from

The Progeria Research Foundation’s programs and services.

We translate information collected within our programs and

services, and develop charts and graphs which track our

progress from year to year.

This allows you to assess where we’ve been, and the

improvements we’ve made for children with Progeria.


PRF By The Numbers: A Data Sharing Tool

Why Sharing Data Is Essential

According to the National Institutes of Health:

“data sharing is essential for expedited translation of research

results into knowledge, products, and procedures to improve

human health.”

http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html

In other words, everyone benefits by knowing and learning as

much as possible about Progeria - the scientific and medical

communities, the public, and the children.

© 2021 The Progeria Research Foundation. All RightsReserved. As of March 31, 2021

http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html

PRF By The Numbers…Here’s How It Works

We take raw data collected through our programs and services,

remove any personal information to protect the participant, and

present it to you in a format that is engaging and informative.

PRF programs and services include:

The PRF International Registry

The PRF Diagnostics Program

The PRF Cell & Tissue Bank

The PRF Medical & Research Database

PRF Research Grants

Scientific Workshops

Clinical Trial Funding and Participation

As of March 31, 2021© 2021 The Progeria Research Foundation. All RightsReserved.

Our Target Audience

PRF By The Numbers is intended for a broad array of users

Families and children with Progeria

The general public and nonscientists of all ages

Scientists

Physicians

The media

This means that different types of slides will be of interest depending

on who is looking at the information. We have designed this slide

set so that you can pull out what is most important to you.

We love suggestions - if you don’t see some facts and figures here

that you think would be informative, please let us know at

[email protected]


mailto:[email protected]

PRF Programs: It All Starts With The Children

Our participants

come from all over

the world. They find

us through our

outreach – the PRF

website, our

publications,

television

documentaries, their

doctors, neighbors,

friends and family.

Patient

Referral

Internation al Progeria

Registry

Diagnostics Program

Cell &TissueBank

Preclinical Research

Clinical Trials

Medical &ResearchDatabase

Weighing-In Program


Program Collaborations For Success

PRF Cell & Tissue Bank Core

Laboratory

PRF Medical & ResearchDatabase

PRF Cell & TissueBank

PRF Diagnostics Program


Sequencing Laboratory

PRF Cell Bank Submission:

Immortalized Fibroblast CellLines

PRF Cell & Tissue Bank : iPS Cell

Line Generation

PRF Cell & Tissue Bank:

Lymphoblast Cell Line

Generation

PRF Clinical Trials

Non-HGPS Progeroid Patient

Diagnosis


Our Program Collaborators

Our collaborating institutions are crucial to our ability to help children with Progeria.

We are extremely grateful for these ongoing partnerships:

Brown University

Location of The PRF Medical & Research Database

Program IRB approval

Hasbro Children’s Hospital

Location of The PRF Cell & Tissue Bank

Program IRB approval

PreventionGenetics

CLIA*-approved genetic sequence testing

Rutgers University Cell and DNA Repository

CLIA*-approved lymphoblast generation and distribution

University of Ottawa

Induced Pluripotent Stem Cell (iPSC)

CLIA*-approved generation and distribution


Our Clinical Trial Collaborators

Our collaborating institutions are crucial to our ability

to help children with Progeria

Harvard University – Associated Hospitals:

Boston Children’s Hospital

Brigham and Women’s Hospital

Dana Farber Cancer Institute

NIH – funded Clinical and Translational

Study Unit at Boston Children’s Hospital


As of March 31, 2021:

HGPS* in the United States:

Progeroid Laminopathies** worldwide:

Number of Living PRF-Identified Cases

Total Number of Children with HGPS and PL** Worldwide:

131

19

60

Progeroid Laminopathies** in the United States: 13

195

*Children in the HGPS category have a progerin-producing mutation in the LMNA gene

** Those in the Progeroid Laminopathy category have a mutation in the lamin pathway

but don’t produce progerin

© 2021 The Progeria Research Foundation. All RightsReserved.

HGPS* worldwide: 135

PRF-Identified Cases Reside In 52 CountriesAfghanistan Brazil Egypt Indonesia Japan Nepal Portugal Spain Togo

Algeria Canada England Iran Kazakhstan Oman Russia Sri Lanka Turkey

Argentina China France Iraq Libya Palestine-Gaza Saudi Arabia Suriname Ukraine

Australia Columbia Germany Ireland Luxembourg Pakistan Serbia Sweden USA

Bangladesh Denmark Honduras Israel Malaysia Philippines South Africa Tajikistan

Belgium Dominican India Italy Mexico Poland South Korea Taiwan

Children and Adults with HGPSChildren and Adults with PLs

135 Known Children and Adults with HGPS and60 with PLs Living around the World as of March 2021

…and Speak 32 Languages

ةسسؤمثاحبأخايشلا

早衰症研究基金會

Progeria रिसिच फाउंडेशन 早老症研究財団

조로증연구재단

బాలుడబ లా కివయస స్ముదరుకండానేవృద్ా పా య్రూప్ంల నోకిి

వచ చ్ుటరసీ రె చ్ుఫ ండ షేన్

Progeria Araştırma Vakfı

прогерии исследовательский фонд


Arabic English Hindi Marathi Russian Ukrainian

Bengali Ewe Indonesian Malay Serbian Urdu

Cebuano Filipino Italian Nepali Spanish

Chinese French Japanese Pashto Tagalog

Danish German Kannada Polish Tamil

Dutch Hebrew Korean Portuguese Turkish

16 17 17 18 19 1922

2629 30 31

293034 35

3741

44 45 46

5254

78

86

0

10

20

30

40

50

60

70

80

90

100

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

Nu

mb

er

of

Ch

ildre

n a

nd

Co

un

trie

s

Year

Countries

Progeria Cases*

Living Children PRF has identified with Progeria and the countries they reside in from 2000 - 2011

* Progeria cases: Total number of known cases include both HGPS & PL

* When a child passes away, numbers are decreased.

Every Year Our Numbers Grow Option Every Year Our Numbers Grow

3539

4346 44 45

4851 52 52

8690

100

107112 112

120

128131

135

10

2225 27

34 3236 38

5760

0

20

40

60

80

100

120

140

160

2012 2013 2014 2015 2016 2017 2018 2019 2020 Mar, 2021

Nu

mb

er

of

Ch

ildre

n a

nd

Co

un

trie

s

Year

Countries

HGPS

PL

Living Children PRF has identified with Progeria and Progeroid Laminopathies and the countries they

reside in from 2012 – 2021*

* Numbers shown for living children as of Dec. 31 for any given year.

* When a child passes away, numbers are decreased.

Every Year Our Numbers Grow Option Every Year Our Numbers Grow

Tracking Children with Progeria Through Prevalence

How does PRF estimate how many children we are searching for,

and in what countries? We use population prevalence.

Prevalence is the proportion of children with Progeria per total

population.


How Prevalence Is Estimated

At PRF, we use a formula based on the number of children

we’ve identified in the US. We then expand that out to the

world population.

We do this because we have the most complete reporting for

the US and since Progeria has no gender, ethnic, or other

biases, we assume that the prevalence in the US is the

same prevalence in other countries.

PRF estimates prevalence for years when the official US

census provides a reliable population number.


USA Prevalence of Progeria

March, 2021 population statistics:

The US population was:

Number of PRF-identified children with HGPS in the US:

19

Prevalence of HGPS in the US: 19 in 331 million is about


*estimates routinely fall between 1 in 18 - 1 in 20 million people.

331,002,651 people

1 in 17 million people

Prevalence and World Population of Progeria

Given the world population as of March 31, 2021

.


Using Prevalence To Find Children In A Certain Country

We can now use the total population estimates for any given country, in order to

understand whether we have found most or all children in a particular country.

For example, as of March, 2021:

Brazil’s population was estimated as

people

Using Prevalence, the number of children living

PRF has identified 7 of these 12 children, and is

searching for the 5 others

with Progeria in Brazil is 213,692,280/17,400,000 = 12

* Data based on the latest United Nations Population Division estimates


213,692,280

International Progeria Registry*


Program Goals:

Patient identification

Outreach to patient families and their physicians

A springboard for program enrollment

Registry forms available athttps://www.progeriaresearch.org/international-registry-2/

*PRF International Registry includes those with genetically confirmed or

clinically suspected Progeria, as well as those with other possible progeroid

syndromes

https://www.progeriaresearch.org/international-registry-2/

325 Children Have Registered With PRF

20 20

36

5461

82

102

118129

151160

181193

208

224

241

254269

285

319325

0

20

40

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Mar,2021

Nu

mb

er

of

Re

gist

ran

ts

Year

© 2020 The Progeria Research Foundation. All Rights Reserved. As of January, 2021

From 65 Countries and 1 TerritoryAlgeria Bulgaria Dominican Republic Guatemala Ireland Mexico Panama Russia Suriname USA

Argentina Canada Ecuador Honduras Israel Morocco Peru Saudi Arabia Sweden Venezuela

Australia Chile Egypt Hong Kong Italy Nepal Philippines Serbia Switzerland Vietnam

Bangladesh China England India Japan Netherlands Poland South Africa Tanzania

Belgium Colombia Finland Indonesia Kazahkstan Oman Portugal South Korea Togo

Bolivia Czech Republic France Iran Libya Pakistan Puerto Rico Spain Turkey

Brazil Denmark Germany Iraq Malaysia Palestine Romania Sri Lanka Ukraine

© 2021 The Progeria Research Foundation. All Rights Reserved.

Children Around the World Registered with PRF

As of March 31, 2021

South America 15.4%

N=50

Europe15.7%

N=51

North America 25.5%

N=83

Asia 35.4%

N=115

Africa6.5%

N=21

Australia 1.5%

N=5

…And All Continents

Participation (%) By Continent


Program Goal:

Genetic Sequence Testing for Progeria-causing mutations

Pre-requisites for Testing:

Registration with PRF International Registry

One or more of the following

Family history – proband, prenatal

Phenotypic presentation – proband, postnatal

Relative of positive proband

Testing information available at:

https://www.progeriaresearch.org/the-prf-diagnostic-testing-program/



https://www.progeriaresearch.org/the-prf-diagnostic-testing-program/


Total Number of Proband Tests Performed:

Exon 11 (HGPS) Mutations:

Other Progeroid Laminopathies (Exons 1 – 12):

Zmpste24 Mutations :

Average Number of Patients Tested Per Year :

Diagnostics Testing Summary

All tests are performed in a Clinical Laboratory Improvement Amendments (CLIA) certified facility.

105

13

2

8.4

154


Mutations Identified Through PRF Diagnostics Program

DNA Mutation Amino Acid Effect ZygosityProgerin

Producing?

Number

Diagnosed

Classic HGPS – LMNA Mutation

1824 C>T, exon 11 G608G heterozygous Yes 91

Non Classic HGPS– LMNA Mutation

1822 G>A, exon 11 G608S heterozygous Yes 4

1821 G>A, exon 11 V607V heterozygous Yes 2

1868 C>G, exon 11 T623S heterozygous Yes 1

1968+5 G>C, intron 11 --------- heterozygous Yes 2

1968+1 G>C, intron 11 --------- heterozygous Yes 3

1968+2 T>A, intron 11 heterozygous Yes 1

1968+1 G>A, intron 11 heterozygous Yes 1

Progeroid Laminopathy– LMNA Mutation

1579 C>T, exon 9 A527C heterozygous No 1

1579 C>T, exon 9 A527C homozygous No 6

1580G>T, exon9 A527L Homozygous No 2

1619 T>C, exon 10 M540T homozygous No 3

331 G>A, exon 1 G111L heterozygous No 1

Progeroid Laminopathy– Zmpste24 Mutation

1274T>C, exon 10 L425P homozygous No 2


17 21 24 24 26 28 29 29 29 29 30 32 33 35 36 36

3746

51 5662

71 76 82 87 94 97107 108

113 116 118

54

6775

8088

99105

111116

123 127

139 141148 152 154

0

20

40

60

80

100

120

140

160

180

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Mar,2021

Nu

mb

er

Te

ste

d

Year

Total Testing LMNA Negative Total Testing LMNA Positive Total Clinically Affected Tested by PRF

*Graph does not include Parents/Siblings tested

Number of Affected Children/Adults Tested and the Number Testing

Positive for LMNA Gene Mutation*

Longitudinal Testing Data for PRF Diagnostics Program


PRF Cell & Tissue Bank

Program Goals:

Provide a resource for researchers worldwide

Ensure the sufficient availability of genetic and biological materials essential for research aimed at understanding the pathophysiology of disease and the links between Progeria, aging and heart disease

Obtain long-term clinical data


Resource information available at: https://www.progeriaresearch.org/cell-and-tissue-bank/

https://www.progeriaresearch.org/cell-and-tissue-bank/

PRF Cell & Tissue Bank Holdings

73 Dermal Fibroblast Lines from affected and parents

124 Lymphoblast Lines from affected, parents and siblings

10 Induced Pluripotent Stem Cell Lines from affected and parents


Total Number of Participants: 286*

6 Immortalized Fibroblast Cell Lines from affected and parents

* Participants may have donated multiple times© 2021 The Progeria Research Foundation. All RightsReserved.

Number Of Cell Lines By Year

20

33 35 36 36 39 42 46

61 65

78 78 78 79 82 86 88 88 88 88

17

29

4454

6269

7480

92100

112 116 116 118121

123 124 124 125 125

37

62

7990

98108

116126

153165

190 194 194 197203

209 212 212 213 213

0

50

100

150

200

250

Nu

mb

er

of

Ce

ll L

ine

s

Year

Total Cell Lines Parents/Siblings CumulativeTotal Cell Lines Affected CumulativeTotal Number of Cell Lines


PRF Cell & Tissue Bank Distribution

Research Teams From Countries Have Received


26200

Cell Lines

DNA Samples

Tissue, plasma, serum

and other biological samples

Lonafarnib Samples

Senescent Progeria

Fibroblasts in Culture


Biological Sample Distribution Over Time

20 20 16

32

1712

92

2429 27

95

62

108

122

168178

135

219

86

20

0

50

100

150

200

250

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Mar,2021

Nu

mb

er

of

Sa

mp

les D

istr

ibu

ted

Year

Fibroblast Lines Lymphoblast Lines iPSC Lines

DNA Immortalized Cell Lines # = Total Distributed


USA Cell & Tissue Bank Recipients


Recipient Institution Recipient Institution

H. Erbil Abaci Columbia University Medical Center

Mansoor Amiji Northeastern University Martin Dorf Harvard Medical School

Angelika Amon Massachusetts Institute of Technology Stephen Doxsey U. of Massachusetts Medical School

Stelios Andreadis U. of Buffalo Jack Elias Brown University School of Medicine

Samuel Beck MDI Biolab Mike Erdos National Institutes of Health

Shelley Berger U of Pennsylvania Jed Fahey Johns Hopkins University

Bruce Blazer U. of Minnesota Toren Finkel NIH

Joseph Bonventre Brigham and Women’s Hospital Shridar Ganesan Cancer Institute of New Jersey

Demetrios Braddock Yale University Abhimanyu Garg U. of Texas Southwestern Medical Center

Jonathan Brown Vanderbilt University Glenn Gerhard Temple University

Ted Brown Institute for Basic Research (IBR) David Gilbert Florida State University

Mark Burkhard University of Wisconsin-Madison Thomas Glover U.of Michigan Medical School

Judy Campisi Buck Institute Robert Goldman Northwestern University

Kan Cao U. of Maryland Susana Gonzalo St. Louis School of Medicine

Li Chai Harvard University Lilian Grigorian Cedars Sinai Medical Center

Francis Collins National Genome Research Institute Gregg Gundersen Columbia University Medical Center

Lucio Comai U. of Southern California Curtis Harris National Institutes of Health

Daniel Conway Virginia Commonwealth University Martin Hetzer Salk Institute

John Cooke Houston Methodist Research Institute Camila Hochman-Mendez Texas Heart InstituteMauro Costa-Mattioli

Baylor College of Medicine Liam Holt NYU Institute for Systems Genetics

Adrienne Cox U. of North Carolina at ChapelHill Steve Horvath UCLA

Greg Crawford Duke University Medical Center Johnny Huard U. of Texas Health Science Center at Houston

Antonei Csoka Howard University Jay Humphrey Yale University

Kris Dahl Carnegie Mellon University Kohta Ikegami The University of Chicago

George Daley Boston Children's Hospital Vishwanath Iyer U. of Texas Austin

Channing Der U. of North Carolina at ChapelHill Jose Jalife University of Michigan

Mohanish Deshmukh U. of North Carolina at ChapelHill David Kaplan Tufts University

Dennis Discher U. of Pennsylvania


Recipient Institution Recipient Institution

Timothy Kowalik U. of Massachusetts Medical School Joseph Rabinowitz Temple University

Dmitri Krainc Massachusetts General Hospital Ana Robles National Cancer Institute

Jan Lammerding Harvard University David Sabatini Whitehead Institute

Dudley Lamming U of Wisconsin-Madison John Sedivy Brown University

Jeanne Lawrence U. of Massachusetts Medical School Christian Sell Drexel University College of Medicine

Joan Lemire Tufts University School of Medicine Jerry Shay UT Southwestern Medical Center

Kam Leong Columbia University Jamila H Siamwala Brown University

Jason Lieb U. of North Carolina at ChapelHill Andrew Sonis Boston Children's Hospital

David Liu Harvard University Ronald St-Louis OVIBIO Corporation, Inc.

Chengzu Long New York University School of Medicine Earl Stadtman National Heart, Lung & Blood Institute

Shigemi Matsuyama Case Western Reserve University Dylan Taatjes U. of Colorado

Rachel Patton McCord University of Tennessee Marc Tatar Brown University

Andrew Mendelsohn Regenerative Sciences Institute Rajarajan Amirthalingam ThandavarayanHouston Methodist Research Institute

Susan Michaelis John Hopkins University School of Medicine Eduardo TorresU of Massachusetts Medical School

Jeffrey Miner Washington University George Truskey Duke University

Tom Misteli National Cancer Institute Tetsuro Wakatsuki InvivoSciences, Inc

Ashby Morrison Stanford University Alan Waldman University of South Carolina

Marsha Moses Boston Children’s Hospital Steve Warren Emory University School of Medicine

Elizabeth Nabel National Heart, Lung & Blood Institute Howard Worman Columbia University

Timothy Osborne Sanford Burnham Medical Research Institute Tom Wight Hope Heart Institute

Junko Oshima U. of Washington Joseph Wu Stanford University

Bryce Paschal U. of Virginia Feng Zhang The Broad Institute

Hamel Patel U. Of California, San Diego Alessandra Zonari OneSkin Technologies

Mary Patti Joslin Diabetes Center You Zou East Tennessee University

Taihao Quan University of Michigan


USA Cell & Tissue Bank Recipients

International Cell & Tissue Bank Recipients

Recipient Institution Country Recipient Institution Country

Andrea Ablasser Global Health Institute Switzerland Christopher Eskiw Saskatchewan University Canada

Vicente Andrés GarciaCentro Nacional de InvestigacionesCardiovasculares

Spain Gerardo Ferbeyre Université de Montréal Canada

Samuel Benchimol York University Canada Lino FerreiraCenter for Neuroscience and Cell Biology (CNC)

Portugal

Martin Bergö Karolinska Institutet Sweden Marco Foiani Instituto FIRC di Oncologia Molecolare ItalyMartin

Enrico Bertini Ospedale Pediatrico Bambino Gesù Italy Alain Garnier Université Laval Canada

Michael Blank Bar Ilan University Israel Yosef Gruenbaum The Hebrew University of Jerusalem Israel

Antonio Campos de Carvalho

Federal University of Rio de Janeiro Brazil Nady El Hajj Hamad bin Khalifa University Qatar

Ana Carrera Centro Nacional de Biotecnologia Spain Robert Hegele University of Western Ontario Canada

Gordon Chan University of Alberta Canada Andreas Hermann University of Dresden Germany

Mario D. CorderoINEBIR- Instituto par el estudio de la Biologia de la Reproduccion Human

Spain Corinne Hoesli McGill University Canada

Lynne Cox University of Oxford England Junho K Hur Kyung Hee UniversityRepublic of Korea

Thomas Dechat Medical University of Vienna Austria Anthony HymanMax-Planck-Institute of Molecular Cell Biology and Genetics

Germany

Annachiara DeSandre-Giovannoli

Laboratoire de Génétique Moléculaire FranceUlrich auf dem Keller Technical University of Denmark

Denmark

Jerome Dejardon Institute of Human Genetics FranceJan Korbel European Molecular Biology Laboratory Germany

Karima Djabali TU-Munich Germany Christian Kubisch Institute of Human Genetics Germany

Ma Dongrui Singapore General Hospital Singapore Varun Kumar Uniklinikum Heidelberg Germany

J. El Molto Molecular World, Inc Canada Kirsztian Kvell University of Pecs Hungary

Maria Eriksson Medicinsk Naringslara Sweden Taejoon KwonUlsan National Institute of Science & Technology

Korea

Chiara LanzuoloCNR Institute of Cellular Biology & Neurobiology

Italy

International Cell & Tissue Bank Recipients

Recipient Institution Country Recipient Institution Country

Caterina La Porta University of Milan Italy Fiorella Piemonte Ospedale Pediatrico Bambino Gesù Italy

Delphine Larrieu University of Cambridge England Neale Ridgway University of Halifax Canada

Lucia Latella National Research Council(CNR) Italy Claudia Ruebe Saarland University Germany

Giovanna Lattanzi ITOI-CNR Unit of Bologna Italy Kanaga Sabapathy National Cancer Centre Singaport Singapore

Jean-Marc Lemaitre Institute of Functional Genomics France Isabella Saggio Sapienza University of Rome Italy

Nicolas Levy Génétique Médicale et Développement France Kanda Sangthongpitag Experimental Therapeutics Centre Singapore

Baohua Liu Shenzhen University China Yasuhiro Shimoyima Shinshu University Japan

Elsa Logarinho Instituto de Biologia Molecular e Celular Portugal Ok Sarah Shin Korea University Guro Hospital Korea

Jun Lu Northeast Normal University China Sanjay Sinha University of Cambridge England

Frank Lyko German Cancer Research Institute Germany Michael Speicher Medical University of Graz Austria

Thorston Marquart University of Münster Germany William Stanford University of Toronto Canada

Felipe AlonsoMassó Rojas

National Institute of Cardiology Ignacio Chávez Mexico

Michael Walter University of Münster Germany

Scott Maynard Danish Cancer Society Research Institute Denmark Herbert Waldman Max Planck Institute Germany

Ohad Medalia University of Zurich Switzerland Miguel Weil Tel Aviv university Israel

Denis Mottet University of Liège Belgium Jesús Vazquez Cobos Haoyue Zhang Spain

Silvia Ortega-Gutiérrez Universidad de Complutense de Madrid Spain Ulrich auf dem Keller Maastricht University The Netherlands

Selma Osmanagic-MyersMax Perutz Labs, Medical Universityof Vienna Austria

Haoyue Zhang Shenzhen Bay Laboratory China

Bum-Joon Park Pusan National University South Korea Alex Zhavoronkov Federal Clinical Research Centre Russia

Center for Neuroscience and Cell Zhongjun Zhou University of Hong Kong China

PRF Medical & Research Database


Program Goals:

Collect the patient health records for living and deceased children with Progeria

Obtain long-term clinical data

Abstract data for longitudinal and cross-sectional analyses

Better understand the clinical disease process in Progeria and aging related diseases

Develop treatment strategies and recommendations for health care professionals and families

Project staff obtain the patient’s medical records and film

studies from birth throughout the participant’s lifespan.

Medical records include visits to: primary care physicians,

specialty physicians, hospital emergency rooms, hospital

admissions, dentists, physical therapy, occupational therapy

and school health records.

Retrospective data abstraction protocol allows for

specifically targeted or broad spectrum of data.


How The PRF Medical & Research Database Works

Enrollment information available at: https://www.progeriaresearch.org/medical-

database/

https://www.progeriaresearch.org/medical-database/

Medical & Research Database Participation

191 Participants are enrolled from countries and US territoryArgentina China Germany Italy Netherlands Puerto Rico Sri Lanka USA

Australia Columbia Guatemala Japan Oman Romania Suriname Venezuela

Bangladesh Denmark Honduras Kazakhstan Pakistan Russia Sweden Vietnam

Belgium Dominica Republic India Libya Peru Senegal Tanzania

Brazil England Indonesia Mexico Philippines South Africa Togo

Canada Egypt Ireland Morocco Poland South Korea Turkey

Chile France Israel Nepal Portugal Spain Ukraine


Database Longitudinal Enrollment

11 11 13 16 1722

27 2731 34 35 36 39 41 42 43

47 48 51 51 51

20 20

31

4348

59

7077

85

99

111117

126132

147152

164

176183

187191

0

50

100

150

200

250

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Mar,2021

Nu

mb

er

of

Pa

rtic

ipa

nts

an

d C

ou

ntr

ies

Year

Cumulative Number of Countries

Cumulative Number of Participants

Children Enrolled in The PRF Medical & Research Database

and the Countries of Residence

As of March 31, 2020© 2021 The Progeria Research Foundation. All Rights Reserved.

Participants with Medical Records Reports:

Types Of Data Collected

Participants with Radiology Studies: 62

166

160°


PRF Weighing-In Program

A sub-program of The PRF Medical & Research Database

Collects weight-for-age data prospectively:

Home scale provided by PRF

Parents weigh child weekly or monthly

Report weights electronically


Weighing-In Program Participation

Participants are enrolled from countries and US territory122

Argentina Canada England Indonesia Mexico Puerto Rico South Korea Turkey

Australia China Germany Ireland Morocco Romania Spain Ukraine

Bangladesh Colombia Guatemala Israel Nepal Russia Sri Lanka USA

Belgium Denmark Honduras Italy Poland Senegal Togo Venezuela

Brazil Dominion Republic India Japan Portugal South

Africa

Tanzania Vietnam

Weighing in Participants Around the World As of April 1, 2019

Participants Enrolled In The PRF Weighing-In Program and

Countries of Residence

2024 26 29 30 31 34 37 39 42 43

4449

56

74 77 8088

99106

118122

20

40

60

80

100

120

140N

um

be

r E

nro

lled

an

d N

um

be

r o

f

Co

un

trie

s(C

um

ula

tive

)

0

2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Year

Number of Countries

Number Enrolled


Data from this program were key in the development of

primary outcome measure for the first drug treatment trial for

Progeria.

As of December 1, 2018, children from The PRF

Weighing-In Program have entered clinical treatment trials

using this data.

Clinical Trials And The Weighing-In Program

Failure to Thrive Starts Towards End of Year One

PRF-Funded Clinical Treatment Trials


Clinical Drug Treatment Trials

Goals:

To define the natural history of

HGPS in quantifiable terms

that will expand our ability to

measure treatment outcome

To assess the safety of new

treatments for HGPS

To measure effects of

treatments for children with

HGPS on disease status,

changes in health, and survival


Current Therapeutic Intervention Strategies

Farnesyl-PP + Preprogerin 1

Preprogerin 2

Preprogerin 3

Progerin

Farnesyl

transferase

Zmpste24

ICMT

AutophagyEverolimus

Key Properties of

Preprogerin/Progerin

not farnesylated;

terminal CaaX box

farnesylated

farnesylated;

terminal aaX cleaved

farnesylated;

carboxymethylatedmTOR

Lonafarnib


Post-translational processing and medications currently under investigation in clinical treatment trials for Progeria. Items in green = enzymes. Items in red = clinical trial medications that inhibit corresponding enzymes. Lonafarnib is a farnesyltransferase inhibitor. Everolimus is a rapamycin analogue that inhibits mTOR and promotes cellular autophagy. FT=farnesyltransferase.

Year Drug(s) Phase Location # Countries

2007-

2010Lonafarnib 2 Boston 29 16

2009

Lonafarnib

Pravastatin

ZoledronateFeasibility Boston 5 2

2009-

2013

Lonafarnib

Pravastatin

Zoledronate2 Boston 45 24

2014-

presentLonafarnib 2 Boston 71 32

2016 –

present

Lonafarnib

Everolimus1/2 Boston 60 27

2018 -

presentLonafarnib 2 Boston

43 from 23 countries enrolled

to date

PRF Funds Clinical Treatment Trials

Participation in PRF Clinical Trials

97 Children have participated in PRF Clinical Trials from countries:

Argentina China England Italy Pakistan Romania Sri Lanka Ukraine

Australia Colombia Germany Japan Peru Russia Sweden USA

Belgium Denmark Honduras Libya Philippines South Africa Tanzania Venezuela

Brazil Dominican Republic India Mexico Poland South Korea Togo

Canada Egypt Israel Morocco Portugal Spain Turkey


Treatment Trial Collaborations For Success

The children are seen by physicians from:

Boston Children’s Hospital

Dana-Farber Cancer Institute

Brigham and Women’s Hospital

Data were also generated by scientists from:

Alpert Medical School at Brown University

Brown University School of Public Health

University of California Los Angeles

National Human Genome Research Institute

Schering-Plough Research Institute

Lonafarnib generously provided by Eiger

Everolimus generously provided by Novartis


Clinical Treatment Trial Efficacy Results

Lonafarnib, a type of farnesyltransferase inhibitor (FTI) is our

first treatment for Progeria.

Results showed improvement in:

Rate of weight gain

Increased vascular distensibility

Improved bone structure

Better neurosensory hearing

Increased Lifespan

Gordon et al, PNAS, 2011


Clinical Trial PublicationsDrug Effect:

Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome.

Gordon et al, JAMA, 2018, 319(16):1687-1695.

Survey of Plasma Proteins in Children with Progeria Pre-therapy and On-Therapy with Lonafarnib. Gordon et al, Pediatric Research,

2018 Jan 17. Epub Ahead of Print.

Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford

Progeria Syndrome. Gordon et al, Circulation, 2016 Jul 12;134(2):114-25.

Seeking a Cure for One of the Rarest Diseases: Progeria. Collins FS. Circulation, 2016 Jul 12;134(2):126-9.

Impact of Farnesylation Inhibitors on Survival in Hutchinson-Gilford Progeria Syndrome. Gordon et al, Circulation, 2014 Jul 1;130(1):27-

34.

Moving from Gene Discovery to Clinical Trials in Hutchinson-Gilford Progeria Syndrome. King et al, Neurology, 2013 Jul 30;81(5):408-9.

Clinical Trial of a Farnesyltransferase Inhibitor in Children with Hutchinson-Gilford Progeria Syndrome. Gordon et al, Proceedings of the National Academy of Sciences, 2012 Sep 24.

Neurologic Features of Hutchinson-Gilford Progeria Syndrome after Lonafarnib Treatment. Ullrich et al, Neurology, 2013, 81:427-430.

General:

Phenotype and Course of Hutchinson-Gilford Progeria Syndrome. Meredith et al, New England Journal of Medicine, 2008, 358(6): 592-604.

Pubertal Progression in Adolescent Females with Progeria. Greer et al, Journal of Pediatric and Adolescent Gynecology, 2017 Dec 17.

Epub Ahead of Print.

Dermatology:

Initial Cutaneous Manifestations of Hutchinson-Gilford Progeria Syndrome. Rork et al, Pediatric Dermatology, 2014,1-7.


Clinical Trial Publications ContinuedDental:

Hutchinson-Gilford Progeria Syndrome: Oral and Craniofacial Phenotypes. Domingo et al, Oral Diseases, 2009, 15(3):187-195.

Cerebrovascular:

Imaging Characteristics of Cerebrovascular Arteriopathy and Stroke in Hutchinson-Gilford Progeria Syndrome. Silvera et al, American Journal of Neuroradiology, 2013 May;34(5):1091-7.

Cardiology:

Cardiac Abnormalities in Patients With Hutchinson-Gilford Progeria Syndrome. Prakask, et al, JAMA Cardiology, 2018, Apr 17;115(16):4206-4211.

Mechanisms of Premature Vascular Aging in Children with Hutchinson-Gilford Progeria Syndrome. Gerhard-Herman M, et al., Hypertension.2012

Jan;59(1):92-97; Epub 2011 Nov 14.

Skeletal:

Hutchinson-Gilford progeria is a skeletal dysplasia. Gordon,et al., Journal of Bone and Mineral Research. 2011Jul;26(7):1670-9.

A Prospective Study of Radiographic Manifestations in Hutchinson-Gilford Progeria Syndrome. Cleveland et al, Pediatric Radiology, 2012 Sep;42(9):1089-

98. Epub 2012 Jul 1.

Craniofacial Abnormalities in Hutchinson-Gilford Progeria Syndrome. Ullrich et al, American Journal of Neuroradiology. 2012 Sep;33(8):1512-8.

Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome. Gordon, CM et al. Bone. 2019 Aug;125:103-111. Epub 2019 May 8.

. Skeletal maturation and long-bone growth patterns of patients with Progeria: a retrospective study. Tsai, A et al,The Lancet. Child and Adolescent Health.

2021. ePub 2021 Feb 28.

Ophthalmology:

Ophthalmologic Features of Progeria. Mantagos et al., American Journal of Ophthalmology, 2017 Jul 27.

Audiology:

Otologic and Audiologic Manifestations of Hutchinson-Gilford Progeria Syndrome. Guardiani et al, The Laryngscope, 2011, 121(10): 2250-2255.

Microbiome at Sites of Gingival Recession in Children with Hutchinson-Gilford Progeria Syndrome. Bassir et al.

Journal of Periodontology. 2018, 89(6): 635-644.© 2021 The Progeria Research Foundation. All RightsReserved. As of March 31, 2021

Program Goals:

Attract high level researchers to the field of Progeria, andprovide the ability for them to thrive in the field

Foster researchers of interest to PRF’s mission

Encourage high quality publications

Stimulate novel research that will lead to larger grants from other resources such as NIH, Ellison Foundation, and others

Projects that are likely to lead to clinical treatment trials within 5 years

Development of gene and cell based therapies to treat Progeria

Grants program information available at https://www.progeriaresearch.org/research-funding-opportunities/


PRF Grants Program

https://www.progeriaresearch.org/research-funding-opportunities/

Back Row (L to R): Tom Glover PhD, Vicente Andrés Garcia PhD, Tom Mistelli PhD, Maria

Eriksson PhD, W Ted Brown MD, PhD, Frank Rothman PhD (emeritus), Bryan Toole PhD(chair)

Front Row (L to R): Monica Kleinman MD, Christine Harling-Berg PhD, Judy Campisi PhD,

Leslie Gordon MD, PhD, Marsha Moses PhD

PRF Medical Research Committee

Volunteer MRC Reviews Grant Applications Semi-annually


PRF Granting Structure


PRF’s research focus is highly translational. Topics must fall within the following research

priorities:

Projects that are likely to lead to clinical treatment trials within 5 years. This includes the

discovery and/or testing of candidate treatment compounds in cell-based or animal models

of HGPS. Only proposals that test compounds in a progerin-producing animal or cell model

will normally be considered. Analyses in non progerin-producing models are acceptable,

but only as a comparison to progerin-producing models and with strongjustification.

Development of gene-and cell-based therapies to treat Progeria

Assessment of natural history of disease that may be important to developing outcome

measures in treatment trials (preclinical or clinical)

Phase I Proposals: Awards are typically for 1-2 years in the range of $75,000/year. PRF will

conduct a thorough cost analysis for each project during evaluations of submissions.

Required Qualifications. Principal investigators must hold a faculty appointment or equivalent.

Awards will be granted only to applicants affiliated with institutions with 501(c)3 tax-exempt

status, or the equivalent for foreign institutions.

Letter of Intent (LOI). A letter of intent is required and must be approved before a full application

will be considered. Instructions to submit a Letter of Intent and grant application information, can

be found at https://www.progeriaresearch.org/grant-application/.

https://www.progeriaresearch.org/grant-application/

As of March 31, 2021, The PRF funding rate is 31%

funded Since inception, grant applications received and

PRF has funded principal investigators from institutions

in countries

Lamina A, progerin, Lamin B in HGPS and aging

Genetics and nuclear function

Preclinical Drug Therapy

Molecular Abnormalities and Therapies

Vascular Pathology

Mouse Models

Stem Cell Investigations and Therapy

Clinical Trials

Grant Funding Rates And Topics

© 2021 The Progeria Research Foundation. All Rights Reserved. * Submissions include Letters of Intent and Full Grants

USA PRF GranteesGRANTEE NAME INSTITUTION GRANTEE NAME INSTITUTION

Richard Assoian University of Pennsylvania Joan Lemire Tufts University of Medicine

Jemima Barrowman Johns Hopkins University Jason Lieb University of North Carolina

Juan Carlos Belmonte Salk Institute for Biological Studies Monica Mallampalli The Johns Hopkins School of Medicine

Ted BrownThe Institute for Basic Research in Developmental

DisabilitiesSusan Michaelis The Johns Hopkins School of Medicine

Abigail Buchwalter University of California, San Francisco Thomas Misteli National Cancer Institute

Kan Cao NIH; University of Maryland Marsha MosesHarvard Medical School; Boston Children’s

Hospital

Christopher Carroll Yale University Junko Oshima University of Washington

Francis Collins National Institute of Health Bryce Paschal University of Virginia

Lucio Comai University of Southern California Joseph Rabinowitz Temple Medical School

John P. Cooke Houston Methodist Research Institute John M. Sedivy Brown University

Kris Dahl Carnegie Mellon University Dale Shumaker Northwestern University

Jed W. Fahey Johns Hopkins School of Medicine Michael Sinensky East Tennessee State University

Toren Finkel NIH Brian Snyder Beth Israel Hospital

Loren Fong UCLA Dylan Taatjes University of Colorado

Michael Gimbrone Brigham & Women's Hospital Jakub Tolar University of Minnesota

Thomas W. Glover University of Michigan Katherine Ullman University of Utah

Robert Goldman Northwestern University Thomas Wight Benaroya Research Institute

Leslie B. Gordon Tufts University School of Medicine; Brown U. Katherine Wilson Johns Hopkins University

John Graziotto Massachusetts General Hospital Stephen Young UCLA

Brian Kennedy Buck Institute for Research on Aging Yue Zou East Tennessee State University

Jan Lammerding Cornell University

Dudley Lamming University of Wisconsin Madison


International PRF Grantees

GRANTEE NAME INSTITUTION COUNTRY

Vicente Andrés Garcia Centro Nacional de Investigaciones Cardiovasculares Spain

Samuel Benchimol York University, Toronto Canada

Martin Bergö Karolinska Institute Sweden

Claudia Cavadas University of Coimbra Portugal

Jesús Vázquez Cobos Centro Nacional de Investigaciones Cardiovasculares Spain

Thomas Dechat Medical University of Vienna Austria

Karima Djabali Technical University of Munich Germany

Maria Eriksson Karolinska Institute Sweden

Gerardo Ferbeyre Université de Montreal Canada

Célia Ferreira de OliveiraAveleira University of Coimbra Portugal

Roland Foisner Medical University of Vienna Austria

Giovanna Lattanzi University of Bologna Italy

Elsa Logarinho University of Porto Portugal

Evgeny Makarov Brunel University England

Silvia Ortega-Gutiérrez Universidad Complutense de Madrid Spain

Bum-Joon Park Pusan National University Korea

Isabella Saggio Sapienza University of Rome Italy

Charlotte Sorenson Centro Nacional de Investigaciones Cardiovasculares Spain

William Stanford University of Toronto Canada

Colin Stewart Institute of Medical Biology Singapore

Ricardo Villa-Bellosta Instituto de Investigación Sanitaria - Fundación Jiménez Díaz Spain

Anthony Weiss University of Sydney Australia

Zhongjun Zhou University of Hong Kong China


Meeting Goals:

To promote

collaboration

between basic and

clinical scientists

toward progress in

Progeria,

cardiovascular, and

aging research PRF

has held 13international

scientific meetings.

PRF Scientific Meetings

13


2020 PRF WorkshopWebinar

These are large multi-day workshops open to all scientists. Clinical and basic researchers spend intense days sharing data and planning new collaborations for progress towards treatments and cure.

Various NIH Institutes have funded all international workshops through R13and other granting mechanisms

Other organizations have also generously sponsored workshops

International Workshops Promoting Global Interest In Progeria,

Cardiovascular Disease And Aging


Growth of Global Interest In PRF Workshops

2030 36

5646 52

3 5 10 10 10 18 14 14

504656

90100

140

180 173156

377

0

50

100

150

200

250

300

350

400

2001 2003 2005 2007 2010 2013 2016 2018 2020

Nu

mb

er

PRF Workshop Year

Number of Posters

Registrant Countries

Registrant Number

© 2020 The Progeria Research Foundation. All Rights Reserved. As of January, 2021

2020 was a webinar. Posters N/A

Subspecialty Scientific Meetings

Small, focused meetings designed to promote and support work in areas of high

interest for Progeria

First Genetics Consortium Meeting – “Searching

for the Progeria Gene”, August 23, 2002, Brown

University, Providence, RI

Second Genetics Consortium Meeting – “Post-

gene Discovery”, July 30, 2003, Bethesda, MD

Bone Marrow Transplant Meeting – “Forging

Ahead by Exploring Potential Treatments”, April

25-26, 2004, National Institutes of Health,

Bethesda, MD

New Frontiers in Progeria Research (2012),

Boston, MA



Scientific articles have been published citing The Progeria Research

Foundation Grants Funding Program

Scientific articles have been published citing PRF Cell & Tissue Bank

resources

Scientific articles have been published citing The PRF Medical & Research

Database

Scientific articles have been published from clinical trial data

See slide #55 and #56

Scientific Publications


163

97

28

23

Publication list available at: www.progeriaresearch.org/prfprp/

http://www.progeriaresearch.org/prfprp/

Progeria Clinical Care Handbook

768

The Progeria Handbook 2nd Edition. A

Guide for Families & Health Care

Providers of Children with Progeria. The Progeria Research Foundation. Leslie B. Gordon

MD, PhD; Medical Director (editor) 2019.

Provided in English, Spanish

and Japanese

Expert contributors from Boston

Children’s Hospital

Number of Progeria Care Handbooks distributed to

families of those with Progeria and their care givers:


The Progeria Research Foundation

Finding…Diagnosing…

Studying…Treating…

CURING

Together We WILL Find The Cure!www.progeriaresearch.org


http://www.progeriaresearch.org/

PRF By The Numbers - Progeria Research Foundation

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