CERSI-FDA Workshop on Prenatal Somatic Cell Gene Therapies
Prenatal Somatic Cell Gene Therapies: Charting a Path Forward for Clinical Applications
Tuesday, October 26, 2021
7 am to 2 pm Pacific time (10 am to 5 pm Eastern Time)
Virtual Workshop - Meeting will be held over Zoom
Overview
As gene therapy gains momentum in treating single gene disorders in pediatric and adult patients, it is an apt time to discuss clinical applications to treat fetuses with severe or fatal genetic diseases. Preclinical data underscore the possible advantages of gene therapy or gene editing before birth: fetal exposure to a missing protein may result in tolerance; treating before formation of the blood-brain barrier may improve neurologic function; and early treatment may improve survival for many progressive diseases, some of which are fatal before birth. There are also risks and other considerations that are particular to prenatal application. We are convening a group of scientists, clinicians, ethicists, patient advocates, and regulatory professionals to assess the risks and benefits of prenatal somatic cell gene therapy (PSCGT) in humans. Discussion will focus on therapies that target somatic cells of fetuses with severe, early onset disorders.
The objective of the virtual workshop is to consider the various scientific, clinical, ethical, and regulatory aspects of prenatal somatic cell gene therapy for fetuses with severe, early onset genetic diseases and to articulate a prudent roadmap for first-in-human clinical applications.
The workshop will:
- Summarize the current state of fetal therapy, including the path to IND for current prenatal medical therapies (stem cell and enzyme replacement therapy).
- Consider the available preclinical data and scientific rationale for prenatal gene therapy in various animal models.
- Review several gene therapy and gene editing strategies currently in clinical trials for postnatal indications, using spinal muscular atrophy as an example.
- Examine principles of fetal and maternal monitoring, informed consent, and patient perspectives in designing a clinical trial.
This virtual collaborative workshop is co-sponsored by the UCSF-Stanford CERSI, the UCSF Center for Maternal-Fetal Precision Medicine, and the U.S. Food and Drug Administration.
Recordings
Agenda
Please click here to download the Speaker Biographies.
Time (PT) | Topic | Speaker |
---|---|---|
7:00 am |
Introduction and Welcome |
Tippi MacKenzie, MD |
7:05 am |
Patient Story: Experience with Prenatal Diagnosis of Severe Genetic Disease |
Billie Lianoglou, LCGC, MS |
SESSION 1: Background on Fetal Diagnosis and Therapy | ||
7:20 am |
Overview of Fetal Therapy Today We will review the current state of fetal therapies offered for anatomic disorders, the evolution to treat severe diseases that are not lethal in utero and evolving medical therapies such as stem cell transplantation and protein replacement. |
Tippi MacKenzie, MD |
7:40 am |
Relevant Diseases for Prenatal Gene Therapy We will review the genetics of disorders that are amenable to prenatal gene therapy (including considerations for genotype/phenotype correlations, severity, and age of onset) and biomarkers to monitor efficacy. |
Stephan Sanders, BMBS, PhD |
8:00 am |
Prenatal Diagnosis We will review the state of prenatal diagnosis for anatomic and genetic diseases, including considerations for identifying genetic disorders that do not have obvious ultrasound manifestations. |
Teresa Sparks, MD |
8:20 am |
Q & A |
|
8:30 am |
BREAK |
|
SESSION 2: Preclinical Data for Prenatal Gene Therapy in Specific Diseases |
||
8:40 am |
MPS1 and Monogenic Lung Disease We will review preclinical data regarding safety and efficacy of CRISPR gene editing in utero to treat mice with MPS 1, as well as data for targeting the fetal lung in a mouse model of surfactant protein deficiency. |
William Peranteau, MD |
8:55 am |
Beta Thalassemia and Cystic Fibrosis We will review data demonstrating the ability to target fetal hematopoietic stem cells using gene editing to treat beta thalassemia in mice. We will also review data on targeting the developing fetal lung to treat CFTR mutation. |
David Stitelman, MD |
9:10 am |
Hemophilia We will review preclinical data from studies of prenatal gene therapy (in mouse, sheep, and non-human primates) to express a clotting factor, as well as evidence of tolerance induction to an exogenous protein after in utero exposure. |
Graça Almeida-Porada, MD, PhD |
9:30 am |
Overview of Available Data on Germline Transduction We will review experiments quantifying exposure to viral vectors after prenatal gene therapy in the sheep model. |
Christopher Porada, PhD |
9:45 am |
Panel Discussion We will discuss how the available preclinical data relate to potential regulatory applications for prenatal gene therapy, as well as remaining scientific gaps to improve safety and efficacy. Panelists: |
Moderator Agnieszka Czechowicz, MD, PhD |
10:15 am |
BREAK |
|
SESSION 3: Considerations for Clinical Translation |
||
10:40 am |
Ethical Consideration for Prenatal Gene Therapy We will discuss considerations for performing clinical trials during pregnancy, as well as considerations for avoiding germline editing in any setting. |
R. Alta Charo, JD |
11:00 am |
Case Scenario for Prenatal Gene Therapy: Spinal Muscular Atrophy We will consider SMA as an example to understand the necessary IND-enabling studies to assess the safety and efficacy of available therapeutics that could be administered prenatally. We will review the scientific rationale for early treatment and available data for using either antisense oligonucleotides or aav gene therapy. |
Charlotte Sumner, MD |
11:30 am |
Preclinical Considerations for Gene Therapy Products: An FDA Perspective This presentation will provide an overview of the preclinical testing program to inform clinical development for gene therapy products. |
Ying Huang, PhD |
12:00 pm |
Procedural Considerations for Delivery of Prenatal Therapies: Intravascular We will review the safety profile of fetal umbilical vein injections, performed commonly for intrauterine transfusions. |
Juan Gonzalez Velez, MD, PhD |
12:10 pm |
Procedural Considerations for Delivery of Prenatal Therapies: Intracerebroventricular We will review considerations for delivery of therapeutics into the fetal cerebrospinal fluid, such as the feasibility of intraventricular injections. |
Nalin Gupta, MD, PhD |
12:20 pm |
Maternal and Fetal Safety Considerations We will review safety considerations of prenatal gene therapy for the mother and the fetus, including protocols to detect potential adverse events during and after pregnancy. |
Anna David, MB ChB, PhD |
12:40 pm | Q & A | |
12:55 pm | BREAK | |
SESSION 4: Balancing Safety and Innovation | ||
1:05 pm | Mila's Path to Truly Personalized Medicine | |
1:15 pm |
Panel Discussion We will discuss the balance between developing life-saving therapies while ensuring safety of clinical trial participants. Panelists: |
Moderator Tippi MacKenzie, MD |
1:55 pm |
Closing Remarks Tippi MacKenzie, MD - University of California San Francisco |
Tippi MacKenzie, MD |
2:00 pm | Adjournment |
Workshop Planning Committee
We thank the following members of the workshop planning committee for their time and expertise:
- Tippi MacKenzie, MD - Chair
- Graça Almeida-Porada, MD, PhD
- Larissa Lapteva, MD
- Lawrence Lin, PhD
- William Peranteau, MD
- Christopher Porada, PhD
- David Stitelman MD
- Evi Struble, PhD
- Members of the UCSF Center for Maternal-Fetal Precision Medicine
Please contact Lawrence Lin at [email protected] with any questions.