UCSF

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.

 

Registration

This meeting is free for all to attend, but pre-registration is required.

Click Here to Register

 

Agenda

Please click here to download the PDF iconSpeaker Biographies.

 

Time (PT) Topic Speaker
7:00 am

Introduction and Welcome

Tippi MacKenzie, MD
University of California San Francisco

7:05 am

Patient Story: Experience with Prenatal Diagnosis of Severe Genetic Disease

Billie Lianoglou, LCGC, MS
University of California San Francisco

  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
University of California San Francisco

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
University of California San Francisco

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
University of California San Francisco

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
Children's Hospital of Philadelphia

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
Yale University

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
Wake Forest

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
Wake Forest

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: 
  Graça Almeida-Porada, MD, PhD - Wake Forest
  Lois Freed, PhD - U.S. Food and Drug Administration
  William Peranteau, MD -  Children's Hospital of Philadelphia
  Christopher Porada, PhD - Wake Forest
  David Stitelman, MD - Yale University

Moderator

Agnieszka Czechowicz, MD, PhD
Stanford University

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
University of Wisconsin at Madison

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
Johns Hopkins University

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
U.S. Food and Drug Administration

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
University of California San Francisco

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
University of California San Francisco

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
University College London

12:40 pm Q & A  
12:55 pm BREAK
  SESSION 4: Balancing Safety and Innovation
1:15 pm

Panel Discussion

We will discuss the balance between developing life-saving therapies while ensuring safety of clinical trial participants.

Panelists: 
  P.J. Brooks, PhD - National Center for Advancing Translational Sciences
  Barbara Koenig, PhD - University of California San Francisco
  Kevin Prohaska, DO, MPH - U.S. Food and Drug Administration
  Fyodor Urnov, PhD - University of California, Berkeley
  Julia Vitarello - Mila’s Miracle Foundation

Moderator

Tippi MacKenzie, MD
University of California San Francisco

1:55 pm

Closing Remarks

Tippi MacKenzie, MD - University of California San Francisco

Tippi MacKenzie, MD
University of California San Francisco

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.