NFXF Webinar Series: Gene Therapy & the FXS Community: A Review of Community Surveys

With Dr. David Hampson, Anna De Sonia, Sarah Eley, Vivian Chen, Marisa Vomvos, and Dr. Rey Lozano

With the possibility of gene therapy getting closer and closer, many researchers are interested in knowing where the Fragile X community stands on the topic; what are the thoughts, feelings, knowledge, concerns, and hopes that come with gene therapy?

There have been many recent surveys that set out to understand this deeper.  During this webinar, expert Dr. David Hampson will lay the groundwork of understanding what gene therapy is and what’s most relevant to the future of FXS research, followed by three different groups (The Patrick Wild Centre, Mt. Siani Hospital, and the NFXF) presenting on their community survey results, with a moderated Q&A to close.

Gene Therapy & the FXS Community: A Review of Community Surveys

“Gene Therapy” for FXS:  What Are the Next Steps Toward Clinical Testing?

Dr. David Hampson, professor in the department of Pharmaceutical Sciences at the University of Toronto, kicked off this webinar with a brief lesson on gene therapy, and how it pertains to Fragile X syndrome (FXS). Below are a few topics and take-away points from this presentation:

• The term “gene therapy,” in its broadest definition, encompasses a variety of different types of potential treatments that act by adding, subtracting/reducing, or changing part of the disease-causing DNA, mRNA, or protein.
• There are many types of gene therapy currently being used and studied.  The four main types of gene therapy today include:
  1. Viral vector based: Uses a non-hazardous and non-replicating virus to transfer the DNA code for a protein into the body.  The most commonly used type for neurological disorders are adeno-associated viral vectors (AAVs).
     Example:  Zolgemsma for treating childhood Spinal Muscular Atrophy (SMA)
  2. Anti-sense oligonucleotides (ASOs): Short stretches of modified DNA that can block the production of a pathological protein, or induce or boost the production (expression) of an endogenous therapeutic protein within cells and tissues.
     Example:  Nusinersen (Spinraza) for SMA
  3. Direct protein therapy: Delivery of a natural protein, or a modified version of a natural protein, that is therapeutic.
     Examples: insulin; BFX-01 in development by Bowen’s FX Therapeutics
  4. CRISPR-mediated gene therapy: Used to modify or “edit” DNA sequences in cells.
     Example:  Casgevy for sickle cell disease
• The AAV technique is one we may likely see in the future of FXS research.
• To date, there are 8 published studies including 7 using the mouse model and 1 study using the rat   model of FXS.  They have all demonstrated effectiveness of AAV-FMRP on a wide variety of biochemical and behavior tests.
• Gene therapy, in general, has been tested in thousands of patients for more than 2 decades.
• There are currently 4 AAV-based drugs that have been clinically approved for use (for other diseases and disorders, not for FXS).
• Very early postnatal treatment may be critical for treatment.
• There is a lot of hope for gene therapy in FXS in the future!

Gene Therapy in Fragile X Syndrome:  A Caregiver Perspective

Sarah Eley, from The Patrick Wild Centre out of the University of Edinburgh discussed her team’s online questionnaire, which specifically aimed to capture the perspectives of family and caregiver views and attitudes towards gene therapy for the treatment of FXS.  Below are key points from this survey done in the UK.

• The survey was comprised of 13 open-ended questions.
• 195 parents and caregivers completed the online questionnaire, with nearly 70% of respondents coming from the UK and Europe, 22% coming from the Americas, and the remaining responses from the rest of the world.
• Overall respondents felt interested, excited and hopeful about gene therapy, with the majority saying they want research into gene therapy for FXS to take place and that they would consider it as a treatment option.
• Strong interest from caregivers of those living with FXS in gene therapy trials taking place and optimism about the impact it could have on their family.
• There is some apprehension and nervousness about unforeseen events.
• Information programs targeted at caregivers are required to allow informed discussions around gene therapy.

Overview of the Mount Sinai Survey on FXS Caregiver Perspectives on Gene Therapy

Vivian Chen, second year genetic counseling student at Mount Sinai, worked in collaboration with Dr. Rey Lozano and genetic counselor Marisa Vomvos on their community survey.  The survey was launched from July-November 2024 with the main goals of assessing caregiver perspectives, attitudes, and knowledge on potential gene therapy for FXS.

• 78 responses in total.
• Most respondents said their main motivator for gene therapy was to improve the quality of life of their loved one living with FXS.
• The top concern for gene therapy was side effects/risks, followed by the concern of cost and effectiveness of treatment.
• 55% of respondents chose Intellectual Developmental Disability (IDD) as their “top FXS symptom to improve” with gene therapy treatment.
• 85% of respondents agreed with the statement “I am hopeful about the success of gene therapy to treat FXS”.
• 84% of respondents agreed with the statement “Gene therapy is something I would consider if it were available”.
• When asked to describe how gene therapy makes one feel, respondents most often reported positive feelings such as hopeful, excited, interested, curious, and optimistic.
• Next steps for Vivian include analyzing these survey data for any further relationships, such as attitudes towards gene therapy as they relate to the severity of one’s condition.

NFXF Gene Therapy Community Survey

Anna De Sonia, Director of Research Facilitation, presented on the National Fragile X Foundation’s mini community survey that was launched in June 2024.  Similar to the previous survey and questionnaire, the NFXF’s survey aimed to get a general understanding of the thoughts and feelings of the greater Fragile X community when it comes to the topic of gene therapy.  Below are high-level results from the survey.

• Over 350 responses in 4 weeks!
• Mini survey – only 8 questions, taking about 5 minutes to complete.
• Most people had some previous knowledge about gene therapy before taking the survey.
• However, most people were unaware of the different types of gene therapy available.
• When asked what people want to know most about gene therapy, results showed the most popular responses were:
  • How does gene therapy work?
  • When will gene therapy be available in FXS?
  • How long do gene therapy effects last?  Is this a cure?
• Top concerns about gene therapy included:
  • Side effects & risks
  • Timeline (when will this be available in FXS?)
  • Treatment frequency (how many times )
  • Effectiveness (is this a cure?)
• Nearly 95% of survey takers said they would consider gene therapy for themselves/their loved ones living with FXS

Panel Discussion

A moderated Q&A with discussion followed the presentations in this webinar.  Below are some of the main take-aways from this discussion.

• Realistically, how far away are we from clinical trials for FXS?
  • Dr. Hampson notes that unfortunately, there are no ongoing clinical trials for FXS.  The next step to move us forward would be for a company (like biotech or pharma) to provide funds to launch an investigational new drug (IND) application to the Food and Drug Administration (FDA) so research can get started with a new clinical trial.  However, even if a clinical trial for gene therapy in FXS was to start tomorrow, it would still take upwards of 3 years to have an answer (and that is best case scenario, so we must be patient).
  • Dr. Lozano adds that though there haven’t been any clinical trials on gene therapy in humans with FXS yet, gene therapy has been tested in humans in many other conditions, reassuring that there is background knowledge and data on safety for when this does enter the Fragile X research space.
• Stem cells and/or cord blood are not used in any current gene therapy methods, and would not be used in gene therapy to treat FXS.
• When clinical trials are available, how are we going to approach self-advocates in situations in which they need to provide consent?
  • This is another stage of development of clinical trials to look into after gauging family and caregiver perspectives.
• Will there eventually be gene therapy that targets other FMR1-related conditions like FXTAS or FXPOI?
  • Genetic counselor Marisa notes that treatment like this is certainly possible in the future, but will have to have a different approach.
  • Dr. Hampson adds that it is much more likely that gene therapy will be tested in FXS before it’s tested in FXTAS or FXPOI.
  • Dr. Hampson also notes that for FXS specifically, gene therapy with a viral vector is the most straightforward case of gene therapy, called gene replacement therapy.  However, this may not be the best case/technique of gene therapy to target and/or treat FXTAS or FXPOI.
• What are you most looking forward to in the future with regard to FXS research and gene therapy?
  • Dr. David Hampson is most looking forward to a foundation or company starting a clinical trial for gene therapy in FXS and hopes it happens soon.  Additionally, he’s looking forward to seeing results from gene therapy studies currently going on in Rett Syndrome.
  • Sarah Eley is looking forward to working with families and being able to offer them something that they’re actually interested in.  She’s hopeful that gene therapy will provide a chance to deliver on this for all those interested.
  • Vivian Chen is looking forward to being able to deliver on the promises of treating the actual cause of FXS and not just its symptoms.
  • Marisa Vomvos acknowledges that there is a lot of uncertainly right now, but there is also a lot of hope, and she’s looking forward to what’s on the horizon.
  • Dr. Rey Lozano is looking forward to being able to offer gene therapy to the patients he sees in clinic one day.
  • Anna De Sonia is looking forward to seeing a treatment for FXS come to fruition, for the entire FX community and the experts who have worked tirelessly to find a cure.

While we wait for gene therapy to become a reality in FXS, remember to lean on your community, your experts, your family, your people, and hang on to your hope!

Additional Resources

We are excited to share information and resources on our website that was referenced during the webinar.  We have included the link to additional resources and information below.

Gene therapy simplified: what is it and how does it work?
Blog giving a simplified description of gene therapy and how it works

Gene Therapy Panel Discussion
Panel discussion with Fragile X experts from the 19th NFXF International Fragile X Conference (July 2024)

MyFXResearch Portal
View and search for ongoing research opportunities near you!  Keep a tab on this – farther down the line – when gene therapy trials are getting started.

The Patrick Wild Centre
For our friends across the pond in the UK, the Patrick Wild Centre is a research center at the University of Edinburgh which aims to better understand genetic conditions affecting brain development, and to improve the care and treatment available for people with these conditions.

Mount Siani Fragile X Syndrome and Fragile X-related Disorders Program
This program at Mount Sinai in New York is dedicated to advancing the care and treatment of individuals with Fragile X-related disorders and to providing specialized services tailored to the unique needs of patients with FXS.

Be sure to stay tuned into the NFXF for more gene therapy content!