Gene Therapy Trials for PID:A Nursing Perspective

Jin Hua Xu-Bayford

Clinical Nurse Specialist Gene Therapy

Email: xuj@gosh.nhs.uk

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