A Rare International Dialogue (Saturday May 11, 2019) Designing Pathways to Patient-Centered Care Bone marrow as a Vehicle for Correction of Rare Disorders: Donna Wall, The Hospital for Sick Children

1. Bone Marrow as a Vehicle for Correction of
Rare Disorders
Dr. Donna Wall
Section Head, BMT/Cellular Therapy
The Hospital for Sick Children
CORD Panel May 2019 Toronto

2. Disclosures
Participating in CRISPR/Vertex clinical trials for treatment of thalassemia
and sickle cell anemia
Consultant for Novartis – not related
Practicing physician in the field of BMT/CT

3. Goals of this talk
Through the description of one approach to gene therapy to
highlight how the tools of bone marrow transplantation are
being used in gene therapy
Highlight factors that will affect the efficacy of this and related
gene-editing strategies – especially patient/family
partnerships

5. The example of thalassemiathalassemia

7. Strategy for gene therapy for thalassemia
*HPFH Hereditary Persistence of Fetal Hemoglobin

8. CRISPR/Vertex

9. Strategy is to prevent the switch by inactivating
BCL11a
CRISPR/Vertex

10. CRISPR/Vertex

11. 11
Clinical Study CTX001-111: Study Outline
Importance of community engagement with the trials
CRISPR/Vertex

12. › Starting over 2 years ago we attended local, regional, and national
meetings of the care communities
- presenting the biology and rationale of the trial
- participating in discussions with patients and families
› Primary providers were enlisted as co-investigators on the trials
› Invited patients to come and talk at academic rounds
› What we learned:
- the disease burden for patients and families was much more than I had
appreciated
- the first patients on these trials are true research collaborators
- early stage trials are not for everyone
Bringing new gene therapies to the thalassemia/sickle cell
community

14. Factors impacting the outcome of a gene
therapy approach
Delivery of
modified cells
Patient age and
disease
HSC number and
quality
Ex Vivo
manipulation
Preinfusion
conditioning

15. Conclusions
Through decades of clinical study and basic biology we have
the understanding of thalassemia and sickle cell and basic
hematopoiesis to design creative gene therapy strategies
Leveraging experience from BMT, genetics, and patients/
families are all important
Importance of engaging the patient community in building the
research agenda

16. Acknowledgements
BMT/Cellular therapy team at
SickKids
Prerna Chopra, Andrea Cote, and
Erilda Kapllani
Physicians, nurses, technologists,
and extended care team
Patients and families
The regional and national
patient/family groups for
thalassemia and sickle cell
anemia
Our colleagues at:

17. THANK YOU
Donna.Wall@sickkids.ca