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 Endocrinology specialty topic page houses video interviews with key opinion leaders in the field of endocrinology about the latest relevant FDA actions, clinical guideline updates, and clinical trial findings related to cell therapies, gene therapies, and engineered and regenerative medicines developed for endocrine disorders. It also contains up-to-date clinical news coverage in the field of endocrinology gene and cell therapy.

Catch up on the latest news, breakthroughs, and announcements from biotechnology companies making advancements in cell and gene therapies. 

Around the Helix: Cell and Gene Therapy Company Updates – November 20, 2024

In observance of World Diabetes Day, held annually on November 14, we took a look back at the past few months' news in cell and gene therapy for diabetes indications.

World Diabetes Day 2024: Looking Back at Progress for Cell and Gene Therapy

Around the Helix: Cell and Gene Therapy Company Updates – November 13, 2024

Around the Helix: Cell and Gene Therapy Company Updates – November 6, 2024

Around the Helix: Cell and Gene Therapy Company Updates – October 30, 2024

The chief medical officer and head of translational research at Ring Therapeutics discussed research presented at ASGCT 2024. 

Chris Wright, MD, PhD, on Annelloviruses, a Potential Alternative to AAV for Gene Therapy 

“We were looking in the body for different viruses that are persisting there, but not causing any problems. So, we did find a number of viruses, the anelloviruses. Anelloviruses actually make up about 80% of all the viruses in a person's body. And it turns out that that they've been there throughout all of the person's life, pretty much shortly after birth. So, they persist for a long period of time, and they don't appear to cause any problems, they don't induce an immune reaction, and they don't seem to have any associations with diseases. So, we thought that could be a great virus to use to try to deliver gene therapy, because it should be a safe approach.”

Ring Therapeutics is developing anellovectors as potential alternatives to adeno-associated virus (AAV) gene therapies. AAV therapies, although currently the standard for gene therapies and an approved modality, have inherent challenges, including immune responses and lack of redosability. Anelloviruses, found naturally in the human body, have potential to address these challenges for gene therapies.

Ring presented data from multiple studies on anelloviruses at 

the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting

, held May 7 to 10, 2024, in Baltimore, Maryland. 

spoke with Chris Wright, MD, PhD, chief medical officer and head, translational research, Ring Therapeutics, to learn more about anelloviruses and the data presented at ASGCT. He overviewed the outstanding issues with AAV therapies and how anelloviruses may address these challenges. He also outlined the different research presented at the meeting, including demonstrating a large payload with anelloviruses, demonstrating transduction in the eye in nonhuman primates, and demonstrating redosability without issue.

Bounoutas GS, Pozsgai R, Gold I, et al. Anellovectors, a Gene Delivery Platform Based on Commensal Human Anelloviruses, Have the Potential to Evade the Immune System and Deliver DNA Payloads to a Broad Range of Tissues in a Redosable Manner. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #203

Videos

Chris Wright, MD, PhD, on Anelloviruses, a Potential Alternative to AAV for Gene Therapy 

The senior researcher at Seattle Children’s discussed the development and validation of A2-CAR-CISC EngTreg cells.

Subhash Tripathi, PhD, on Generating In Vivo CAR With A2-CAR-CISC EngTreg Cells

"Altogether, our A2-CAR engineered system for the first time demonstrated that we can also provide endogenous production of CAR and successfully generated this A2-CAR engineered Treg project using LV and dual edit approach. And overall, what we can say is that this platform may have implications of treating or use in transplant, autoimmunity or other inflammatory diseases... I think it is a very exciting field, with providing antigen assist to CARs we can not only treat a particular but a broad range of immune diseases."

The lab of David Rawlings, MD, at Seattle Children’s Hospital, has been working on developing and improving regulatory T-cell (Treg) therapies for therapeutic use in transplantation, autoimmune and/or autoinflammatory disease, including diabetes type 1 and multiple sclerosis, among others. These cells are termed CAR-CISC EngTreg cells. One such product from this research is A2-CAR-CISC EngTreg cells, data from the development and validation of which were presented by Subhash Tripathi, PhD, senior researcher at Seattle Children’s and a member of Rawlings' lab, at 

, held May 7 to 10, 2024, in Baltimore, Maryland.

A2-CAR-CISC EngTreg cells are designed to generate HLA-A*02 antibody-based chimeric antigen receptor (CAR) Treg cells in vivo by use of dual homology-directed-repair gene editing. The cells demonstrated specific targeting and no cases of graft versus host disease in early mice studies. CGTLive spoke to Tripathi to learn more about the development of CAR-CISC EngTreg cells, and specifically, developing antigen specific for HLA-A*02 cells, A2-CAR-CISC EngTreg cells. He gave an overview of how these cells were generated and their validation in early mouse studies.

Tripathi SK, Dahl NP, Grimm A, et al. HLA-A2 CAR/IL-2-CISC Engineered Treg Exhibit Robust In Vitro and In Vivo Efficacy. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #90

Subhash Tripathi, PhD, on Generating In Vivo CARs With A2-CAR-CISC EngTreg Cells

The senior researcher at Seattle Children’s discussed advantages of engineered Tregs compared with natural Tregs. 

Subhash Tripathi, PhD, on Developing Safe, Specific Engineered Treg Cell Therapy 

“There are disadvantages associated with current adaptive cell therapies, which are based on natural regulatory T-cells. To cite some of those key technical hurdles, there is a huge rarity of these populations in vivo. So if you get them, you have to scale up for manufacturing, which is very difficult, and then they are very unstable and have plasticity. They have a very poor engraftment in vivo. And sometimes, if you get these cells from patients, they might be defective.”

CAR-CISC EngTreg cells may have therapeutic potential in transplantation, autoimmune and/or autoinflammatory disease, including diabetes type 1 and multiple sclerosis, among others. The lab of David Rawlings, MD, at Seattle Children’s Hospital, has been working on developing and improving regulatory T-cell (Treg) therapies for these uses. A member of the Rawlings lab, Subhash Tripathi, PhD, senior researcher at Seattle Children’s, presented findings from the development and validation of Treg therapies, the final iteration of which was an A2-CAR-CISC EngTreg cell, at 

A2-CAR-CISC EngTreg cells use dual homology-directed-repair gene editing to generate HLA-A*02 antibody-based chimeric antigen receptor (CAR) Treg cells. Early mice studies demonstrate specific targeting and no cases of graft versus host disease. CGTLive spoke to Tripathi to learn more about the research he has done at the Rawlings lab with Treg cells. He gave an overview of the development of engineered Treg cells and their advantages over natural Treg cells.

The Don and Marilyn Anderson Professor of Oncology at University of Wisconsin – Madison shared highlights of discussion. 

Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary 

“I shared the kickoff plenary of the ISCT, which is branded as La Présidentielle. The whole idea is to bring in leaders of sister societies to come and speak to us about what's the mission and vision, for us to have an understanding of the broader ecosystem of cell and gene therapy, especially for knowledge-based societies like ours... there is sort of a common theme in Europe, the UK, the US, that there are so called deserts where there are commercially approved products but eligible patients, especially if they live in rural areas and are of modest means, even though they’re eligible to receive the treatment, don't receive it. How do you tackle that?”

The presidential plenary of the International Society for Cell and Gene Therapy (ISCT) 2024 Meeting, held in Vancouver, Canada, from May 29 - June 1, brought together leaders of sister scholarly societies, including Anna Sureda, MD, PhD, president of European Society for Blood and Marrow Transplantation; Amander Clark, PhD, president, International Society for Stem Cell Research; and Corey Cutler, MD, MPH, FRCP(C), president, American Society for Transplantation and Cellular Therapy, with Jacques Galipeau, MD, president, ISCT, chairing the session, to discuss the current state of development with cell and gene therapies and challenges that the process faces, within each country and internationally.

 spoke with Galipeau to learn more about the plenary and the highlights discussed between the speakers. He shared the different perspectives that each speaker brought to the discussion, with Sureda speaking about the state of development in Spain with the European Medicines Agency. One challenge, Galipeau noted, was relevant regardless of country, and that is tackling the problem of “deserts” in the treatment landscape.

Galipeau J, Sureda A, Clark A, Cutler C. La présidentielle. Presented at: ISCT 2024 Meeting, held in Vancouver, Canada, from May 29 – June 1.

The Don and Marilyn Anderson Professor of Oncology at University of Wisconsin – Madison shared highlights from the discussion. 

The associate professor of otolaryngology from Harvard Medical School also shared his excitement for the positive data on AAV1-hOTOF.

Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials 

“This clearly shows how this kind of collaborative approach can really advance medical discovery much more rapidly, and in the end will help everybody… So that I think is one of the very important messages. We need to have this kind of collaboration, we can do more… to find out where the patient population comes from, to treat more patients, to do more trials, and then we can have a new treatment out quicker.”

AAV1-hOTOF gene therapy yielded significant, clinically meaningful improvements in hearing in 5 of 6 children with autosomal recessive deafness 9 (DFNB9) caused by mutations of the OTOF gene. The clinical trial assessing AAV1-hOTOF is being conducted in collaboration with investigators from Mass Eye and Ear at the Eye & ENT Hospital of Fudan University in Shanghai, China.

Investigators observed no serious adverse events or dose-limiting toxicities. The improvements included hearing recovery, improvements in speech recovery, and significant reductions in the average auditory brainstem response. One participant did not have a response to AAV1-hOTOF, and the investigators theorized that the nonresponse may have been due to their higher concentration of neutralizing antibodies at baseline, or, alternatively, a possible leakage of the AAV1-hOTOF solution from the round window membrane during or after surgery.

 spoke with study investigator Zheng-Yi Chen, DPhil, associate scientist, Eaton-Peabody Laboratories, Mass Eye and Ear, and associate professor, Otolaryngology–Head and Neck Surgery, Harvard Medical School, to learn more about the international trial and the collaboration that allowed it and enriched it. He shared his excitement for the positive data and adding to the body of supporting literature for gene therapy in general.

Lu J, Wang H, Cheng X, et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. 

. Published online January 24, 2024. doi: 10.1016/S0140-6736(23)02874-X

The cofounder, chairman, and CEO of Kriya Therapeutics discussed the company’s goal of bringing gene therapy to a much broader population of patients.

Shankar Ramaswamy, MD, on Bringing Gene Therapy to Common Diseases

“The technology has really matured to a point where we can take that next leap as a field to bring gene therapies into a broader universe of diseases. I think we as a field need to figure out how we can scale the technology, how we can bring down the cost, and how we can improve throughput and quality of the products that we engineer and manufacture. But those are solvable challenges.”

Gene therapy, particularly adeno-associated virus vector-based gene therapy, first gained its foothold in the field of medicine by targeting relatively rare inherited disorders like Duchenne muscular dystrophy and hemophilia A, both of which are now among the indications for the 6 FDA-approved AAV vector-based gene therapies. Indeed, this trend has continued, with many companies and academic institutions continuing to pursue the development of AAV vector-based gene therapies for rare and even ultrarare genetic disorders. Because of the high cost and lengthy and complex manufacturing process for gene therapy products, targeting smaller patient populations for both clinical trials and commercial products is in some ways a good fit for the modality. That said, gene therapy may have the potential to treat much more common diseases, as well. One company currently seeking to bring AAV vector-based gene therapy to common diseases is Kriya Therapeutics. Kriya gave 6 presentations regarding their work on this endeavor at 

, held May 7 to 10, 2024, in Baltimore, MD.

® sat down with Shankar Ramaswamy, MD, the cofounder, chairman, and CEO of Kriya Therapeutics, to learn more about the company’s efforts. Ramaswamy explained that gene therapy has significant potential to address unmet needs for relatively common diseases like type 1 diabetes and geographic atrophy, but that bringing gene therapy to such indications will require overcoming challenges such as scaling manufacturing, reducing costs, and characterizing products. He noted that Kriya is currently working on technologies and methods to address these concerns, and gave his view that gene therapy is on the precipice of reaching much broader use in clinical practice.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

Head of Seattle Children's Research Institute's Center for Immunity and Immunotherapies discussed overcoming limitations of Treg cells via genetic engineering

David Rawlings, MD, on the Potential of Engineered Treg Cells to Treat Autoimmune Diseases

“Putting this all together: The concept of therapy with regulatory T-cells is that if you can target them to the autoimmune tissue of interest—for example, the islet in type 1 diabetes, where the autoimmune process is taking place—then you can have a tissue-specific therapeutic that that turns off an autoimmune process.”

T-regulatory (Treg) cells have the natural ability to dampen immune responses, and as such are of great interest for potential use in the treatment of autoimmune diseases. Although, a number of factors makes the utilization of unmodified Treg cells unlikely to be effective as the basis of a cell therapy. For example, Treg cells require the presence of interleukin-2 (IL-2) in order to remain active and polyclonal Treg cells have limited efficacy. 

In an attempt to overcome challenges like this, investigators in the lab of David Rawlings, MD, the director of the Center for Immunity and Immunotherapies at Seattle Children's Research Institute, have been conducting preclinical research on the development of antigen-specific engineered regulatory T-cells (EngTregs). These EngTregs are derived from autologous CD4 T-cells and are genetically modified to maintain the Treg cell phenotype continuously and to target a specific antigen. A third modification allows the EngTregs to be activated by the presence of rapamycin rather than IL2. This is important because administration of sufficient levels of rapamycin for the purpose of activating the EngTregs avoids common issues with using exogenous IL2, such as activation of other, unintended cell types. These results from their work were presented at 

the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting

, held May 16-20, in Los Angeles, California.

™ shortly after the conference, Rawlings discussed the engineering techniques his lab has been researching and how they might help to overcome the issues holding back the therapeutic potential of Treg cells. He also went over the results of further research that involved administering EngTregs in a mouse model of diabetes. He noted that a mouse surrogate of the EngTregs targeted at mouse pancreatic islet cells showed the ability to prevent the development of diabetes in vivo.

REFERENCE
Seattle Children’s Researchers Share Progress at American Society of Gene and Cell Therapy Annual Meeting. Website. Seattle Children’s Research Institute. Accessed October 12, 2023. https://www.seattlechildrens.org/research/featured-research/asgct-2023/

The director of the Center for Immunity and Immunotherapies at Seattle Children's Research Institute discussed preclinical research on overcoming limitations of Treg cells through genetic engineering.  

The director of the Alleghany Health Network Institute of Cellular Therapeutics discussed possible applications of the procedure.

Massimo Trucco, MD, on the Potential of Islet Cell Transplant

“Chronic pancreatitis can lead to cancer. So, that is a consideration for doing the auto transplant in children to avoid a problem that can develop in the future. In adults, the organs are already working sub-optimally and the cell-to-liver transplant is not the best because the liver is not the best. The general body of the recipient is not working very well.”

The pancreatic islet cell replacement therapy VX-880 reduced insulin dependence in the first 2 patients with type 1 diabetes (T1D) treated as part of a phase 1/2 study (NCT04786262).

Islet cells are emerging as a possible approach to cell therapies in such indications including T1D and chronic pancreatitis.

Recently, Alleghany Health Network performed the first islet cell transplant for the treatment of chronic pancreatitis.

The project leader is Massimo Trucco, MD, director, Alleghany Health Network Institute of Cellular Therapeutics. As part of the treatment, Trucco and colleagues remove the pancreas to eliminate the chronic pancreatitis and transplant islet cells to the liver to continue insulin production.

spoke with Trucco to learn more about the islet cell transplant procedure. He discussed eligibility and potential other applications for the transplants.

1. Markmann JF, Naji A, Rickels MR, et al. Stem cell–derived, fully differentiated islet cells for type 1 diabetes. Presented at: ADA 82nd Scientific Sessions Conference, June 6, 2022, New Orleans, Louisiana. Abstract #259-OR.
2. AHN performs its first islet cell transplants to treat chronic pancreatitis. News release. AHN. October 5, 2021. https://www.prweb.com/releases/ahn_performs_its_first_islet_cell_transplants_to_treat_chronic_pancreatitis/prweb18241294.htm

The director of the Alleghany Health Network Institute of Cellular Therapeutics discussed possible applications of the procedure. 

Massimo Trucco, MD, on the Potential of Islet Cell Transplant 

The director of the Alleghany Health Network Institute of Cellular Therapeutics discussed islet cell transplant for the treatment of chronic pancreatitis.

Massimo Trucco, MD, on Improving Access to Islet Cell Transplant

“We are working very hard to make the auto transplant also available, which uses the same procedure for the allo-transplant in which you can take the islet cell from any diseased donor. Transplant in a diabetic patient is technically the same thing and is very feasible.”

Islet cell transplant is emerging as a cell therapy approach to treat conditions including type 1 diabetes (T1D) and chronic pancreatitis. Recent data from Vertex Pharmaceuticals showcased the efficacy of this approach, with VX-880 reducing insulin dependence in the first 2 patients with T1D treated in a phase 1/2 study (NCT04786262).

Alleghany Health Network recently performed its first islet cell transplant to treat chronic pancreatitis under the lead of Massimo Trucco, MD, director, Alleghany Health Network Institute of Cellular Therapeutics.

 As part of this procedure, the pancreas is removed to avoid the effects of chronic pancreatitis and islet cells are transplanted into the liver to maintain insulin production.

 spoke with Trucco to learn more about islet cell transplant as a treatment for chronic pancreatitis and T1D. He discussed improving access to the procedure.

The director of the Alleghany Health Network Institute of Cellular Therapeutics discussed islet cell transplant for the treatment of chronic pancreatitis. 

Massimo Trucco, MD, on Improving Access to Islet Cell Transplant  

The Director of the Islet Transplant Program at the University of Alberta discussed the implantable VC-02 device's success in type 1 diabetes.

Stem Cell Therapy Device Restores Insulin Production in T1 Diabetes: James Shapiro, MD

This content originally appeared on our sister site, 

Novel cell replacement therapies have recently produced promising data in several severe diseases, including type 1 diabetes (T1D).

One such study is evaluating a stem cell therapy to restore insulin productinon in people with severe T1D. The ongoing, first-in-human phase 1/2 study has enrolled implanted a total of 17 patients with the ViaCyte PEC-Direct device at 6 different centers. The device is comprised of pancreatic cells (PEC-01) contained within pouches for subcutaneous placement.

In an interview with HCPLive, James Shapiro MD PhD, Canada Research Chair and Director of the Islet Transplant Program at the University of Alberta and lead author of the Cell Reports Medicine report, discussed the findings of the study and what they ultimately represent.

“It was a very successful trial in terms of demonstrating the safety, it was absolutely safe for patients, while they were, you know, many different potential side effects on the anti rejection drugs and the minor surgeries that the patients went through, they tolerated the placement and the removal of the devices exceedingly well,” Shapiro said.

The trial results indicated 34% of patients had evidence of C-peptide production, while 63% of patients had evidence of surviving insulin producing cells at different time points when the devices were taken out and examined under a microscope.

Shapiro went on to describe the next wave of trials using gene-edited products that will not require anti-rejection drugs, called PEC-QT. He noted the difference between a treatment and a cure is the limitless source of cells and lack of need for rejection drugs.

“I think if that happened, then we really would have a therapy that could be given to children just diagnosed with diabetes, they could be given to patients with all forms of diabetes, not just patients with T1D,” he said. “So, I think this does herald a big step forward for for stem cell based therapists in the cure potential curative treatment for all forms of diabetes.”

The Director of the Islet Transplant Program at the University of Alberta discussed the implantable VC-02 device's success in type 1 diabetes.



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