Heather Band

BDFA Scientific Officer

What is Batten Disease?

Batten disease, the Neuronal Ceroid Lipofuscinoses (NCLs) are several different genetic life-limiting neurodegenerative diseases that share similar features.

Batten disease are ‘Simple’ Genetic Diseases

RecessiveInheritance

Types of Batten disease

‘CLN’ genes CLN1

CLN8 CLN2

CLN3

CLN6

CLN5

CLN10

CLN7CLN1/PPT1 (Infantile) CLN2/TPP-I (Late Infantile)

CLN3 (Juvenile)CLN5-CLN8 (Variant)

CLN10/CTSD (Congenital)

CLN6 (Adult recessive)CLN4/DNAJC5 (Adult dominant)

Identified in 2011

CLN11/GRN, CLN12/ATP13A2CLN13/CTSF, CLN14/KCTD7

Identified in 2012

Lysosomes

cvcv

Breakdown & recycling of waste fails

XNeuron

The BDFA was founded in 1998 by a group of parents with affected

children and with the help of Contact a Family and Seeability.

The aim then, as now, was to ensure that no family face the devastating diagnosis of Batten disease alone.

The BDFA has three main aims

To raise awareness

and advocate for

better services and

treatments

To directly fund

research into

potential therapies

and ultimately a cure

To support families

and the

professionals who

work with them

BDFA Research Strategy

• The BDFA funds research into all forms of the NCLs

• Funding excellence in research

• Partner with universities, foundations & charities

• Proactive in our relationships with key stakeholders

• Innovative approach

• Support families funding research

Basic research Identify Targets

Drug discovery

Therapy development

Pre clinical testing

Clinical Trials Treatments

Support and Advocacy for families on BMN190 clinical trial in the UK and worldwide

DanioVisionLocomotion detection systemZebrafish studies

Freeman Family

Gene therapy to treat visual failure in CLN6/3Include other NCLs

Uncovering fundamental differences in cell biology in CLN5

Development of screen using Patient derived CLN5 cells

Assessing the efficacy of gene therapy upon neuropathology in CLN5 sheep

Cell based system for CLN3

NCL International Registry

Italy

Alessandro Simonati MD

University of Verona

Norway

Ingrid Helland, MD

Oslo University Hospital

Denmark

Jon R. Ostergaard, MD

Aarhus University Hospital

France

Catherine Caillaud MD PhD

INSERM, Paris

Turkey

Meral Topcu, MD PhD

University Children’s Hospital, Ankara

Argentina

Ines Noher de Halac, MD

Universidad Nacional de Cordoba

Brazil

Charles Lourenco, MD PhD

University of São Paulo

USA

Ron Crystal, MD PhD

Weill Cornell Medical College

Germany

Angela Schulz, MD , Co-ordinator

University of Hamburg

UK

Ruth Williams, MD

GSTT, London

Finland

Laura Aberg

Folkhälsan, Helsinki

India

Pratibha Singhi, MD

PGIMER, Chandigarh

NCL Patient Registry

= participating countries

PhD Studentships

£15,000- £20,000

STIPEND

£5,000+

FEES/TRAVEL/TRAINING

£5,000-£8,000

CONSUMABLES

0

5

10

15

CK/JonCooper

TK/JonCooper

MV/SaraMole

DM/SaraMole

KW/ ClaireRussell

LP/ BrendaWilliams

OC/JeffreyGerst

£ 0

00

Matched Funding-PhD studentships

Cardiff University

Stipend - £40,000

BDFA, on behalf of Battle Batten

consumables - £25,000

Uncovering fundamental differences in cell biology in CLN5Dr. Emyr Lloyd-Evans & Katie Shipley3-year project

Testing Gene Therapy in CLN5 Sheep

Ana Assis, Prof. Jon Cooper, PSDL; David Palmer & Nadia Mitchell, Lincoln, NZ

CLN5 sheep at Lincoln University, NZ

Drug repurposing in Batten diseaseFishing for a Cure

Why use zebrafish?

Mahmood et al., 2003

CLN2 Severe phenotype

CLN2Wild-Type SiblingNormal Appearance

Wild-Type CLN2

CLN2 zebrafish screen of FDA-approved library

560 compounds19 re-tested1 remained positive (RVC1)

Effect of RVC1 on CLN2 zebrafish

[Please note: this slide has been removed

as it contained unpublished research results]

Gene therapy at the eye

The aim of this 3 year PhD project was to investigate whether a gene therapy is feasible to improve vision in Batten Disease.

Introduce healthy copies of the faulty gene

Institute of Ophthalmology

Prof. Robin Ali, Dr. Sander

Smith

MRC Laboratory of

Molecular Cell Biology

Dr. Sara Mole

Retinal gene therapy

AAV2/5

Inner retinal gene therapy

50 μm

25 μm

Merge projection image

Merge single image magnification

AAV.7m8, intravitreal injection at postnatal day 6 – CMV promoter

Sophia kleine Holthaus

Retinal CLN6 gene therapy

[Please note: this slide has been removed

as it contained unpublished research results]

Co-ordinator Professor Sara Mole

PIs from 13 organisations in 8 different countries, including BDFA

DiseaseModelsIden fica onof

SurrogateMarkers

LeadIden fica on&Op miza on

Drug&GeneTherapeu cStrategies

PrepareforClinicalTrials

WP01+WP04 WP02+WP03 WP05+WP06 WP07+WP08 WP09

Pre-discovery Discovery Pre-clinical

Developing new therapies for

Batten DiseaseCLN3, CLN6 & CLN7

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 666918

BATCure Administrator

BATCure AdministratorAppointed on 30th April 2016

Laura Codd

lauracodd@bdfa-uk.org.uk

Wednesdays 9:30am-5:30pm

£210,000

• 2012-2016

• PhD Studentship CLN3, CLN6 (3-Year)

• Post Doctoral studies CLN3, CLN6 (1-Year)

£437,000

• 2016-2019

• Post Doctoral studies CLN3, CLN6 & CLN7 (3-Years)

• Post Doctoral studies CLN2 (3-Years)

Conclusion• Excellence in science

peer review & setting priorities for research

• Partnerships are keyUniversities, Foundations

• Proactiveseeking matched funding, ensuring continuity of funding

• Innovative approachutilise a range of resources

• Provide a mechanism for individual families to fund research

BDFA Research PartnersDr. Claire RussellGini Brickell MScDr. Fahad MahmoodKaren and Martin Freeman

Professor Jon Cooper Dr. Benda WilliamsDr. Tytus MurphyAna Assis

Prof. Sara Mole Prof. Robin AliDr. Sander SmithDr. Sophia HolthausProf. Paul GissenDr. Dan Little

Dr. Emyr Lloyd-EvansDr. Luke HaslettKatie ShipleyBattle Batten Campaign