gene therapy trials for pid:a nursing perspective jin hua xu-bayford clinical nurse specialist gene...
TRANSCRIPT
Gene Therapy Trials for PID:A Nursing Perspective
Jin Hua Xu-Bayford
Clinical Nurse Specialist Gene Therapy
Email: [email protected]
Thechildfirstandalways
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
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."
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
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)
Entry criteria for the trials
Trial Entry Criteria for SCID-X1
Molecularly confirmed diagnosis No MSD, MFD or fully matched MUD GTAC approval Parental/guardian voluntary consent
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
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
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
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
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
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
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
Patients treated at GOSH
X-SCID (10 patients)ADA SCID (3 patient)X-CGD (2 patients)
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
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
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
Parental Support
Numbers of children being treated remain very small
Parents support parents MDT offer information and support Medical and nursing experiences
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
6th October 2006