COVID Vaccines and Gene Therapy

Authors: This statement was modified with permission from a statement written by Veronica Hood, PhD at the Dravet Syndrome Foundation, with edits from Tanya Brown, PhD, Rachel Bailey, PhD, and Brenda Porter, MD, PhD

There has been some worry in the rare disease communities about the approaches that COVID-19 vaccines are using and how they may interact with future gene therapy approaches for specific disorders.

Two of the current vaccines approved in the United States (Moderna and Pfizer) use RNA enclosed in a lipid droplet. The lipid droplet itself has not been shown to create any sort of immune reaction and none of the components of these vaccines remain long-term in your body. The RNA-based Moderna and Pfizer vaccines should not pose any risk to future gene therapy approaches.

Two other vaccines that are approved in the US and/or are being used in other countries (Johnson & Johnson and Astra-Zeneca) use DNA enclosed in an adenoviral vector. An adenoviral vector is basically a modified “shell” of an adenovirus; the virus’s genetic material has all been removed and scientists have co-opted the “shell” to send in genetic material that they want. The components of these vaccines, as the RNA ones described above, will not remain long-term in your body. However, different from the lipid droplet, the adenoviral vector itself can cause your immune system to react. When your immune system reacts to something, it creates a memory of how to best recognize that foreign molecule and quickly remove it. This means there is a potential risk with an adenoviral vector that your immune system would recognize exposure to a future adenoviral vector and react to it.

The genetic therapy that is progressing towards use in a clinical trial (Taysha Gene Therapies, TSHA-105) for the treatment of SLC13A5 Deficiency should not be at risk for an interaction with any of the vaccine approaches discussed above. TSHA-105 (developed by Taysha Gene Therapies) is DNA delivered by an adeno-associated viral (AAV) vector. An AAV vector is derived from a different type of virus than an adenovirus, and the two should not pose cross-immunogenicity risk. So, receiving a vaccine delivered by an adenovirus vector should not create any issues with receiving a gene therapy delivered by an AAV vector (like TSHA-105).

However, there are other groups working on gene therapy options using adenovirus vectors, and they may become a reality in the future. It is possible that the adenovirus vector vaccines could pose a potential risk to a successful genetic therapy approach that uses an adenovirus vector in the future. There are many types of adenoviruses, and many people naturally encounter adenoviruses in the environment and develop some level of immunity, so it is not a certainty that this would necessarily cause an issue. 

While there is still much we do not understand, the take-home is that there is possibly a risk that vaccines delivered with adenovirus vectors (such as Johnson & Johnson or Astra Zeneca’s COVID-19 vaccines) could create an issue with a future gene therapy, but there is at this time not thought to be a risk to the gene therapy that is progressing towards use in a clinical trial (Taysha Gene Therapies). The currently approved RNA-based vaccines (Pfizer and Moderna), are not a concern for any likely gene therapy trial.

 

How TESS Impacts the Wider Medical Community–by Deepti Dubey, PhD

Deepti Dubey, PhD is a Scientific Officer for TESS Research Foundation. Here Dr. Dubey discusses how the work that TESS Research Foundation spearheads is having a broader impact on our epilepsy community and on neurological disease in general.  

The Search for A Cure
TESS Research Foundation was formed to fund the science to discover a treatment and cure for SLC13A5 Deficiency, a genetic form of epilepsy that begins in babies within hours after birth. While the Foundation’s research efforts are focused specifically on SLC13A5 Deficiency, these scientific breakthroughs have a huge potential to benefit not only patients with uncontrolled epilepsies, but also patients with other neurological disorders.

An Important Piece in a Larger Puzzle
Similar to children diagnosed with SLC13A5 Deficiency, people suffering from a large number of other epileptic disorders have seizures that cannot be controlled with any drug currently available. What this means to the broader epilepsy community is that there is a dire need to find more treatment options for controlling seizures. TESS Research Foundation is currently funding a project for the discovery of new therapeutic molecules for controlling seizures in SLC13A5 Deficiency, which could potentially be used for treatment in other uncontrolled epilepsies.

The Foundation has also initiated a Gene Therapy project for the treatment of SLC13A5 Deficiency. This could be one of the breakthrough efforts in using gene therapy for the treatment of epileptic disorders. Knowledge from this project will have direct impact on the scope of gene therapy in similar epileptic or neurological disorders.

Other efforts include working together with Stanford Children’s Health to design a matrix for all epileptic and movement disorders beginning in infancy. This project aims to help clinicians improve diagnosis of the disease, use more precise therapeutic options and also determine the effectiveness of a new treatment in a clinical trial.

The Path Forward
We at TESS Research Foundation realize that the brain functions as an intricate network of proteins connected with each other through various pathways. Opening a knot of one protein such as SLC13A5 can help detangle a lot of other pathways (diseases).

Our research efforts, although focused on a specific rare disease, have a potential impact on a wider medical community – and to the millions of people who suffer from these types of devastating neurological conditions worldwide.

Update from Dr. Brenda Porter, Scientific Advisory Board Member

I wanted to take a moment to update everyone on the TESS Research Foundation’s accomplishments!  Sometimes in this very fast-paced world we do not take the time to reflect on where we have been and where we are going.

Scientific Advisory Board

The Scientific Advisory Board of TESS Research Foundation is a small group of dedicated researchers that strive to guide the TESS Research Foundation towards a cure for SLC13A5 Deficiency. We do not receive a salary from the foundation, so every dollar that you donate goes directly toward the scientific research that will lead to a cure.

What have we managed to do with your contributions?

 

Reviewed Grants and Project Proposals

We’ve reviewed grants and project proposals to ensure that they have the best chance of leading to an eventual cure for SLC13A5 and meet the industry’s rigorous scientific standards. You can read more about the proposals we were able to fund here. Sadly, we were not able to fund as many proposals as we would have liked, so we ask that you please continue to donate to TESS Research Foundation so that you can help fund future research proposals!

Applied for Grants to Fund Projects

With our assistance, researchers were able to apply for grants from large funding organizations, like the National Institute of Health (NIH). The researchers were then able to use that funding in their SLC13A5 studies. Providing the funds to support the development of preliminary data means that the preliminary data from TESS funded research can go much further. Does this work? YES!

Wrote Letters Explaining the Importance of Studying the Transporter

These letters build more support for research projects and have recently helped Dr. Da-Neng Wang at NYU obtain his NIH grant. The grant is now funding his project, which is titled, “Molecular mechanisms of citrate transporter NACT and its mutations that cause pediatric epilepsies.”

What are we working on now?

We’re working to enable collaborations among researchers around the world.  There are ongoing efforts towards:

A few other items that require your attention:

Bio-bank

TESS Research Foundation is trying to create a Bio-bank so that any researcher with an interest in studying SLC13A5 Deficiency can quickly and easily obtain patient samples. If you want to participate and can provide samples, please check out this form on how you can send your blood/tissue samples to the Bio-bank. If you want to help but can’t provide any samples, then please donate to help fund the Bio-bank.

Quantifying Symptoms to Facilitate a Clinical Trial

We’re currently running a project to measure and quantify the neurological symptoms in patients. This is so that when a therapy becomes available, the clinical trial will have a ready-to-go outcome measure. So, when you get an email from us in your inbox, please give some of your valuable time to answer our questions about your family member’s symptoms and capabilities.

Congratulations!

Congratulations to Drs. Anne Murphy and Ana Pajor, our research grant recipients from 2017. They were able to obtain NIH funding for their project, “Metabolic role of the neuronal Na+ dependent citrate transporter implicated in epilepsy.” You can read more about their project on our website’s research section.

Thank you!

There is a whole lot more to learn and many other things in the pipeline, but please know that we keep moving forward towards a cure with YOUR help.