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
Recessive
Inheritance
Types of Batten disease
‘CLN’ genes
CLN1
CLN1/PPT1 (Infantile)
CLN2/TPP-I (Late Infantile)
CLN3 (Juvenile)
CLN5-CLN8 (Variant)
CLN10/CTSD (Congenital)
CLN7
CLN8
CLN6 (Adult recessive)
CLN4/DNAJC5 (Adult dominant)
Identified in 2011
CLN3
CLN6
CLN5
CLN11/GRN, CLN12/ATP13A2
CLN13/CTSF, CLN14/KCTD7
Identified in 2012
CLN10
CLN2
Lysosomes
Breakdown & recycling of waste fails
Neuron
X
c
v
c
v
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 support families
and the
professionals who
work with them

To raise awareness
and advocate for
better services and
treatments

To directly fund
research into
potential therapies
and ultimately a cure
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
Development
of screen using
Patient derived
CLN5 cells
Cell based
system for
CLN3
Basic research
Identify
Targets
Uncovering
fundamental
differences in
cell biology in
CLN5
Support and Advocacy
for families on BMN190
clinical trial in the UK
and worldwide
Gene therapy to
treat visual failure
in CLN6/3
Include other NCLs
Drug
discovery
Therapy
development
DanioVision
Locomotion
detection system
Zebrafish studies
Freeman
Family
Pre clinical
testing
Clinical Trials
Treatments
Assessing the
efficacy of gene
therapy upon
neuropathology
in CLN5 sheep
NCL International Registry
NCL Patient Registry
= participating countries
Norway
Ingrid Helland, MD
Oslo University Hospital
USA
Ron Crystal, MD PhD
Weill Cornell Medical College
Germany
Angela Schulz, MD , Co-ordinator
University of Hamburg
Denmark
Jon R. Ostergaard, MD
Aarhus University Hospital
Argentina
Ines Noher de Halac, MD
Universidad Nacional de Cordoba
Italy
Alessandro Simonati MD
University of Verona
UK
Ruth Williams, MD
GSTT, London
Finland
Laura Aberg
Folkhälsan, Helsinki
France
Catherine Caillaud MD PhD
INSERM, Paris
Turkey
Meral Topcu, MD PhD
University Children’s Hospital, Ankara
Brazil
Charles Lourenco, MD PhD
University of São Paulo
India
Pratibha Singhi, MD
PGIMER, Chandigarh
PhD Studentships
£15,000
- £20,000
£5,000+
£5,000
-£8,000
STIPEND
FEES/TRAVEL/
TRAINING
CONSUMABLES
15
£ 000
10
5
0
CK/Jon
Cooper
TK/Jon
Cooper
MV/Sara
Mole
DM/Sara
Mole
KW/ Claire
Russell
LP/ Brenda
Williams
OC/Jeffrey
Gerst
Matched Funding-PhD studentships
Uncovering fundamental differences in cell biology in CLN5
Dr. Emyr Lloyd-Evans & Katie Shipley
3-year project
Cardiff University
Stipend - £40,000
BDFA, on behalf of Battle Batten
consumables - £25,000
Testing Gene Therapy in CLN5 Sheep
CLN5 sheep at Lincoln University, NZ
Ana Assis, Prof. Jon Cooper, PSDL; David Palmer & Nadia Mitchell, Lincoln, NZ
Drug repurposing in Batten disease
Fishing for a Cure
Why use zebrafish?
Wild-Type Sibling
Normal Appearance
CLN2
Mahmood et al., 2003
CLN2
Severe phenotype
Wild-Type
CLN2
CLN2 zebrafish screen of FDA-approved library
560 compounds
19 re-tested
1 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
AAV.7m8, intravitreal injection at postnatal day 6 – CMV promoter
Merge projection image
Merge single image magnification
50
μm
Sophia kleine Holthaus
25
μm
Retinal CLN6 gene therapy
[Please note: this slide has been removed
as it contained unpublished research results]
Developing new therapies
for
Batten Disease
CLN3, CLN6 & CLN7
Co-ordinator Professor Sara Mole
PIs from 13 organisations in 8 different countries, including BDFA
Pre-discovery
Disease Models
WP01 + WP04
Iden fica on of
Surrogate
Markers
WP02 + WP03
Discovery
Lead
Iden fica on &
Op miza on
WP05 + WP06
Pre-clinical
Drug & Gene
Therapeu c
Strategies
WP07 + WP08
Prepare for
Clinical Trials
WP09
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 666918
BATCure Administrator
BATCure Administrator
Appointed on 30th April 2016
Laura Codd
[email protected]
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 key
Universities, Foundations
• Proactive
seeking matched funding, ensuring continuity of funding
• Innovative approach
utilise a range of resources
• Provide a mechanism for individual families to fund
research
BDFA Research Partners
Dr. Claire Russell
Gini Brickell MSc
Dr. Fahad Mahmood
Karen and Martin Freeman
Professor Jon Cooper
Dr. Benda Williams
Dr. Tytus Murphy
Ana Assis
Prof. Sara Mole
Prof. Robin Ali
Dr. Sander Smith
Dr. Sophia Holthaus
Prof. Paul Gissen
Dr. Dan Little
Dr. Emyr Lloyd-Evans
Dr. Luke Haslett
Katie Shipley
Battle Batten Campaign