Cellular Delivery of Protein Therapeutics for the Treatment of Amyotrophic Lateral Sclerosis Using Endogenous Retroviruses
Abstract
Applicability of the research: Amyotrophic lateral sclerosis (ALS) is a currently incurable chronic disease that results from the death of nerve cells that are needed to transmit signals from the central nervous system to muscle cells. As a result of this process, patients increasingly lose control over their voluntary muscles and most patients eventually die from the disease within 3-5 years. There are currently only two approved treatments for patients with ALS and neither increase the patient’s survival. Novel therapies are urgently needed. While the causes of ALS differ substantially from patient to patient, 97% of ALS patients share one common disease process: The excessive build-up of proteins inside the nerve cells that can cause the cells’ death. Other groups have previously developed drugs that when artificially delivered into the diseased cells are able to efficiently reduce this build-up and increase cell survival in the lab setting. However, to date no efficient methods exist to deliver these drugs into diseased nerve cells in patients. Using our extensive expertise in the engineering of cell therapies, we are now developing a new cell therapy for patients with ALS to deliver these previously developed drugs to the affected nerve cells. In our approach the engineered cells will act as living drug factories that are constantly producing and delivering the drugs to reduce protein build-up to stop or delay disease progression. Over the course of this project we will (1) establish that this new cell-based therapy is effective at reducing protein build-up and able to stop or delay disease progression and (2) carry out essential engineering work to enable efficient manufacturing of this new therapy. Cell therapies have had remarkable clinical success in other diseases over the past decade not least due to their ability to carry out their therapeutic functions in the patient’s body for years. We hypothesize that this ability of the engineered cells to persist for long periods of time will be particularly useful in the case of ALS as it allows the persistent targeting of an also persistent central disease process. What type of ALS patient will the research help and how will it help them? We anticipate that this new treatment will be particularly effective for patients with a more recent diagnosis of ALS because it has been shown that, in later stages of the disease, ALS cells can acquire additional defects that eventually prevent them from efficiently removing the built-up proteins. Similar to treatments for other neurodegenerative diseases, we envision a disease-modifying mechanism of action for our approach, that will delay or even stop symptom onset and/or disease progression by reducing or preventing death of nerve cells. What are the potential clinical applications, benefits, and risks? There are different options for the clinical application of our approach. Over the past 10 years, over 1,000 clinical cell therapy trials have been performed in the U.S., each relying on the clinical-grade production of the respective cell therapy product. Manufacturing processes for these trials were either centralized to be performed by a relatively small number of dedicated manufacturing sites throughout the country or decentralized using specialized equipment allowing cell therapy production at individual hospitals. As, at its core, our new approach represents a conventional cell therapy engineered using the same processes needed for production of other cell therapy products, we envision clinical translation to be straightforward, requiring relatively minimal work to develop clinical trial protocols and establish/ scale up clinical-grade production. If successful, we believe that this approach will result in few toxicities as it specifically targets ALS-associated protein build up and that it has the potential to delay or stop symptom onset and/or disease progression. Projected time to achieve a patie
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310195
Entities
People
- Tim Luetkens
Organizations
- United States Army
- University of Maryland, Baltimore