Gene therapy and editing

Question and answers with Loren Peña, MD, PhD

Written November 2018

We asked Dr. Loren D.M. Peña six questions from families about gene therapy and editing which is an evolving discussion with lots of questions. Dr. Peña is a clinical geneticist with a strong interest in new gene discovery and development of new therapies for rare disorders. As an investigator in the Undiagnosed Diseases Network at Duke, she was part of the team that described the initial cohort of individuals with ASXL2 disorders. She is also a clinical trialist in the rare disease space and has been involved in studies utilizing the most cutting edge technologies, including gene therapy

Question 1: What is gene therapy and gene editing? What is the difference?

“Gene therapy provides a missing gene or gene activity. It is usually employed in disorders where the problem is what we call ‘loss of function’ which means that the activity of the gene is lost. Gene editing is a method to go directly into the person’s genome and correct (‘edit’) the error in the person’s DNA that led to the genetic condition.”

Question 2: Do you think that gene therapy is a near reality for ASXL syndromes? Or what is the time frame that gene therapy could become a possibility?

“In order to know whether gene therapy, or another approach, is a treatment option for ASXL syndromes, we need to understand the mechanism of disease. As an example, we talked about the conflicting information in the field regarding the mechanism of disease in ASXL3 (Bainbridge Ropers syndrome) and how some of the data supported a model called haploinsufficiency (mutations that lead to half of the activity of this gene, which is insufficient and leads to disease) versus dominant negative (the mutation leads to a gain of activity that disrupts the original function). The first step in thinking about a treatment for any of the ASXL disorders is to gain a better understanding of 1. The function of each of the genes, and 2. How the mutations that lead to ASXL disorders are creating problems in function.”

Question 3: Will the CRISPR gene editing technique be able to correct all types of mutations, including deletions and duplications, or just point mutations?

“There have been publications in which deletions and duplications are generated, so it sounds like the technology may be able to address different types of mutations. However, we are still learning about potential uses, so time will tell what types of mutations can be addressed.”

Question 4: How would you determine what cases would be the first candidates for gene therapy?

“Clinical trials require input from the pharmaceutical company or investigator who is leading them along with the Food and Drug Administration (FDA). Eligibility criteria is set after extensive conversations that include pre-clinical data from animal studies and patient safety concerns.”

Question 5: What are the possible side effects of gene therapy?

"It depends on the type of viral vector that is used. In general, liver injury is always a consideration.”

Question 6: What does gene therapy entail from the patient? How long does it take and what determines the amount of treatment?

“The logistics depend on the mode of delivery and dose. The delivery can be intravenous (IV), into muscle, into parts of the brain. It depends on the target organ and how effective the viral vector is in reaching the intended target organ.”

Medical disclaimer: This website does not provide medical advice. Our website contains general medical information about congenital ASXL mutations. This information is not medical advice and should not be treated as such. You should always talk to your or your family member’s health care professionals for diagnosis and treatment, including information regarding which drugs or treatment may be appropriate for you or your family member. We do not represent or warrant that any particular treatment is safe, appropriate or effective for you or your family member. In the event of a medical emergency, you should contact your doctor immediately or call 911.