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Gene Therapy Trials for PID:A Nursing Perspective
Jin Hua Xu-Bayford
Clinical Nurse Specialist Gene Therapy
Email: [email protected]
Thechildfirstandalways
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Outline of talk What is Gene Therapy Gene Therapy trials at GOSH What are the procedures Entry criteria Ethical/Safety Issues Preparation of the family Post gene therapy follow up monitoring
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Gene Therapy Advisory Committee (GTAC) definition of Gene Therapy
"The deliberate introduction of genetic material into human somatic cells for therapeutic, prophylactic or diagnostic purposes."
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Two Types of Gene Therapy Somatic gene therapy involves
introducing a “good “ gene into targeted cells with the end results of treating the patient-not the future children
Germline gene therapy involves modifying the genes in egg or sperm cells, which will then pass any genetic changes to future generations as well
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Trials under taken at GOSH
X-Linked Severe Combined Immunodeficiency (SCID-X1), now it is closed
Adenosine Deaminase Deficiency (ADA- SCID)
X-Linked Chronic Granulomatous Disease (X-CGD)
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Entry criteria for the trials
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Trial Entry Criteria for SCID-X1
Molecularly confirmed diagnosis No MSD, MFD or fully matched MUD GTAC approval Parental/guardian voluntary consent
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Entry Criteria for X-CGD
Molecularly Confirmed diagnosis X-CGD At least one severe infection needing
hospital treatment, or sever inflammation due to CGD
No MSD, MFD or fully matched MUD GTAC approval Parental/guardian voluntary consent
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Entry criteria trial for ADA
Molecularly Confirmed diagnosis of ADA-SCID
Failure of PEG-ADA No HLA identical family donor GTAC approval Parental/guardian voluntary consent
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How parents choose GT vs BMT Percentage of survival following gene
therapy is greater than following a MUD SCT.
Fear of chemotherapy Fertility issues for the child Shorter hospitalisation with gene therapy Safer treatment, at least in the short
term
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Decision making GT remains a largely experimental and
innovative treatment Currently undergoing clinical trials with
PID One centre in the UK is treating Children
using this form of therapy Rapidly expanding field Media attraction / publicity
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Preparation of the family Begins once a diagnosis of ADA or X-
linked SCID has been established Tissue typing for family to search a MFD Medical team approaching GTAC-seek
approval for gene therapy Consultation with immunology and BMT
consultants Independent consultation
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Other factors Availability of the vector Laboratory resources to prepare the cells Theatre space for the child to have a
bone marrow harvest Availability of UCLH laboratory for CD34
selection Availability of a bed on the appropriate
unit
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Administration of Gene Transduced cells Apply principles of BM/ PBSC infusion Via blood giving set Over 30-40 minutes Ensure appropriate cover
prescribed( Chlorphenamine & Hydrocortisone)
Less likely to react as own cells given back
Usually on a Friday afternoon
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Patients treated at GOSH
X-SCID (10 patients)ADA SCID (3 patient)X-CGD (2 patients)
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Immune reconstitution post gene therapy
4-6 weeks, natural killer (NK) cells start recovering
Approx 12 weeks, T-cells start recovering
Approx 6 months, CD4 should be reaching 300
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Risks and side effects of Gene Therapy
3 Paris patients developed T cell Leukaemia
2/3 were the youngest patients (<3 months)
2 patients in remission and 1 died
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Ethical / Safety Issues
GTAC - Gene Therapy Advisory Committee Not germ line (eggs and sperm) gene
therapy -only somatic cells (body cells) are corrected
Theoretical risk of harm from virus Risk of malignancy- insertional mutagenesis DoH health record flagging Informed consent Unknown risks as novel procedure
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Parental Support
Numbers of children being treated remain very small
Parents support parents MDT offer information and support Medical and nursing experiences
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GTNo/minimal conditioningNo GvHDImmediately availableHigh chance of immune recovery
Risk of leukaemiaLong term recoveryUnknown problems
V effective therapyHigh chance of immune recoveryLarge body of experience
Wait to find donorGvHDShort/Long term SFx of conditioningLong term recoveryBMT
Balancing clinical risk and benefit
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6th October 2006