O SlideShare utiliza cookies para otimizar a funcionalidade e o desempenho do site, assim como para apresentar publicidade mais relevante aos nossos usuários. Se você continuar a navegar o site, você aceita o uso de cookies. Leia nosso Contrato do Usuário e nossa Política de Privacidade.
O SlideShare utiliza cookies para otimizar a funcionalidade e o desempenho do site, assim como para apresentar publicidade mais relevante aos nossos usuários. Se você continuar a utilizar o site, você aceita o uso de cookies. Leia nossa Política de Privacidade e nosso Contrato do Usuário para obter mais detalhes.
Batten Animal Research NNeettwwoorrkk ((BBAARRNN))::
VVaarriiaanntt IInnffaannttiillee BBaatttteenn DDiisseeaassee
BARN is an international collaboration set up to coordinate studies of animal
models of Batten disease.
We share resources, experiments and grants, exchange students, visit each
other and plan together.
WHAT THIS MEANS
Increasing understanding of the
normal function of NCL proteins will
increase the likelihood of successful
Gene therapy using AAV vectors for
CLN5 and CLN6 sheep are in
progress. Sheep were treated at
2-3 months of age (Nov/Dec 2013).
Analysis of disease progression using
the biomarker tests we have
developed is ongoing.
BARN has shown the benefits of
collaboration with increased
research outputs, sharing of
resources and funding, increased
student opportunities and
two-way information sharing with
People: Professor David Palmer, PhD students,
Nadia Mitchell Janet Xu, Jarol Chen, Katharina
Russell and our invaluable animal technicians.
Focus: Disease mechanisms and developing
therapies, gene injections, biomarkers,
neuroinflammation, providing neural cell cultures
Resources: CLN5 affected Borderdales and
CLN6 affected South Hampshire sheep.
People: Dr. Stephanie Hughes, PhD students
Nicole Neverman and Hannah Best, Hollie Wicky,
Dr. Lucia Schoderböck and Kristina McIntyre
Focus: Gene therapy vectors for sheep gene
therapy trials. Modelling pathology of Batten
disease in neuronal cultures and the effectiveness
of drug and gene therapies. Understanding how
the disease-causing mutations affect the biology of
Resources: Vector development and neural
People: Associate Professor Imke Tammen,
PhD student, Izmira Mohd Ismail, technical
support, and Sydney U veterinary staff
Focus: Molecular characterisation of animal
models for NCLs, disease progression and
behaviour studies of the affected Merino flock
Resources: CLN6 affected Merino sheep
and genetics laboratory
Collaborators: Professor Sir John Walker, Mitochondrial Biology Unit,
MRC, Cambridge, Professor Jenny Morton, Cambridge University and
Professor Jon Cooper, Kings College, London; and their colleagues
KEY RECENT RESEARCH
Neuronal cultures from both CLN5 and CLN6 sheep
models are showing us the very early stages of disease,
and suggesting potential drug targets to halt these.
These cells are being used to understand the normal
function of CLN5 and CLN6 proteins and to rapidly
screen drug and gene therapies.
Measures of disease progression (biomarkers) such as
behavioral and sight testing, CT and MRI scanning and
inflammatory markers have been developed.
These biomarkers are being used in our gene and drug
therapy trials to access their effectiveness.
The mutations in the two sheep CLN6 forms and the
CLN5 form have been identified, and the effects of these
mutations on protein function studied in neuronal culture
and sheep tissues.
Analysis of the neuroinflammatory cascade during
disease development aim to identify new drug targets.
GENE THERAPY TRIALS IN CLN5 AND CLN6 DISEASE
Previous lentiviral gene therapy trials showed limited
effect due to the small spread of the viral vector.
Adeno-associated virus (AAV) tests in sheep show
significant spread of gene products throughout the brain
(brown staining in figure).