Alice Cheng, MD is an Endocrinologist at Trillium Health Partners and Unity Health Toronto and an Associate Professor at the University of Toronto.

Alice Cheng, MD: Exploring the Link Between Diabetes and Dementia

22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC)

, Alice Cheng, MD, an endocrinologist at the University of Toronto, discussed the connection between 

 and dementia, highlighting the complex mechanisms, including inflammation, brain insulin resistance, and metabolic disturbances.

Although glycemic control has not been shown to reduce dementia risk, observational data suggest that certain diabetes drugs, like metformin, pioglitazone, GLP-1 receptor agonists (GLP-1 RA), and sodium-glucose co-transporter 2 (SGLT2) inhibitors, may offer protective benefits for cognitive function, with some exploratory studies, such as the REWIND study with dulaglutide, showing the potential improvements in cognition in some patients.

Cheng emphasized the need for larger, randomized controlled trials to better understand the impact of these drugs on dementia, with promising studies underway, including Phase 3 investigations into oral semaglutide’s effect on Alzheimer’s disease, as well as oral semaglutide plus intranasal insulin. She also noted that while lifestyle factors like healthy eating, physical activity, and weight management remain critical for brain health, glycemic control should still be prioritized for overall health. Finally, Cheng recommended routine cognitive assessments in clinical practice, particularly in patients on insulin, to detect dementia early and ensure safe medication management.

Reflecting on the past year, Cheng highlighted the increasing role of GLP-1 RAs, particularly in managing conditions like chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF), with studies like FLOW and drugs like tirzepatide offering exciting new insights into these medications' broader potential.

Relevant disclosures for Cheng include AstraZeneca, Bayer, Eli Lilly, Novo Nordisk, Sanofi, and others.

Cheng A. Diabetes, Drugs, and Dementia Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.

Alice Cheng, MD, discusses the impact of diabetes on cognitive function and the emerging role of diabetic drug classes in dementia care. 


Alice Cheng, MD

Arnold Meshkov MD. is a cardiologist, heart health expert, and was a Professor of Medicine at Temple University School of Medicine until 2015 when he returned to private practice. He is Board Certified in Internal Medicine, Cardiology, and Echocardiography and has lectured on a broad range of topics in cardiology and bioethics. Dr. Meshkov served for many years as the Chairman of the Ethics Committee at Temple University Hospital and was the coordinator of Cardiology Grand Rounds, a weekly lecture series at Temple. 

Arnold Meshkov, MD

Reframing Diabetes Guidelines to Address Real-World Barriers, with Athena Philis-Tsimikas, MD

Despite decades of progress in diabetes care, stark disparities remain in outcomes among patients, especially when it comes to complications linked to poor disease management. While clinical guidelines outline what to prescribe, they rarely address how to ensure equitable access or implementation. Social determinants of health, cultural context, and systemic barriers all play major roles in whether patients can benefit from evidence-based care. As outcomes for diabetes-related complications begin trending in the wrong direction after years of decline, it’s increasingly clear that tackling these external factors is essential.

Athena Philis-Tsimikas, MD, corporate vice president of Scripps Whittier Diabetes Institute at Scripps Health in San Diego, California, gave a talk exploring the impact of social determinants of health at the 

2025 American Diabetes Association (ADA) Scientific Sessions

spoke with Philis-Tsimikas to learn more about how these non-medical factors can affect the health of people with diabetes. She also shared some ways that clinicians can engage with their patients’ social determinants of health that may be affecting their outcomes, and some strategies that her center employs to help address these factors. She emphasized the need for clinical guidelines on treating diabetes to consider non-medical factors of health and how to navigate them in their recommendations.

“The clinical guidelines give us great information on which drugs to use, which technology to use, but they don't necessarily tell us how to overcome some of these other barriers that exist,” Philis-Tsimikas said.

“Social determinants of health, as well as other determinants, the digital divide, cultural adaptations, all these other things that are important as well. So being able to offer a systematic approach on how to overcome this within the guidelines, I think, is important, in addition to all the other terrific information that is in the current guidelines.”

Philis-Tsimikas's disclosures include Dexcom, Lilly, Medtronic, Sanofi, and Novo Nordisk.

Philis-Tsimikas A. Nonmedical Factors That Influence Diabetes-Related Complications. Presented at: 2025 ADA SciSessions; June 20-23; Chicago, Illinois.

Philis-Tsimikas emphasized the impact of nonmedical factors on health and how clinicians can be cognizant of them in their patient management.

Athena Philis-Tsimikas, MD

Brian Kim, MD, is vice chair of research in dermatology at the Icahn School of Medicine at Mount Sinai and director of the Mark Lebwohl Center for Neuroinflammation and Sensation.

A group of 9 experts reflect on what they are looking forward to most in 2025 following the AAD annual meeting. 

Expert Perspectives: Dermatology's Top Story to Watch in 2025

Although nearly all medical professionals can point to a “flagship” meeting or annual conference for their specialty, few serve the same role as or measure up to what the 

American Academy of Dermatology annual meeting

A testament to the draw and magnitude of the AAD’s annual showcase, the 2025 annual meeting, which was held in Orlando, Florida, from March 07-11, 2025, had more than 20,000 registered attendees. In addition to being the field’s largest meeting, one of the unique aspects of the AAD annual meeting is its placement on the calendar. While many organizations opt for end of year or mid-year meetings, the AAD annual meeting typically occurs in Q1 and, for many, sets the tone for the remainder of the year.

With this in mind, the editorial team of HCPLive Dermatology included a simple question on the end of our interviews from the meeting with 9 leading subject matter experts in dermatology: “What is going to be the most important storyline to watch for dermatology for the rest of 2025?”

In the above video, we highlight the perspectives of these experts. Below, you can find a brief summary of the backgrounds and expertise of each individual included in this feature video.

, is a professor and vice chair for Diversity, Equity, and Inclusion at the Perelman School of Medicine. She also serves as president of the American Academy of Dermatology.

, is chairman at Innovaderm Research. He is also the principal investigator of the ICONIC-LEAD trial, which was presented at AAD 2025.

, is a dermatologist and internal medicine specialist with Riverchase Dermatology.

, is an associate professor of Dermatology for the USC Keck School of Medicine. She is the founding director of the USC Skin of Color and Pigmentary Disorders Program and also the president of the Skin of Color Society.

, is the owner of Medical Dermatology Specialists, chief of inpatient dermatology at BannerHealth, and the founder of US Dermatology Partners.

, is a dermatologist and the medical director at the SKiN Centre for Dermatology.

, is an associate professor in dermatology at the Yale School of Medicine.

, is the director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital and the co-chair of the American Academy of Dermatology Acne Guidelines Work Group.

, is vice chair of research in dermatology at the Icahn School of Medicine at Mount Sinai and director of the Mark Lebwohl Center for Neuroinflammation and Sensation.

Brian Kim, MD

Gil Yosipovitch, MD, presented a talk titled ‘Managing Itch’ at the 

Revolutionizing Atopic Dermatitis (RAD) Conference

Yosipovitch is known for his work as a professor of dermatology at the Miller School of Medicine at the University of Miami and Director of the Miami Itch Center. In a recent Q&A interview by 

, Yosipovitch’s responses to various questions related to the management of pruritus, or itch, in atopic dermatitis were highlighted:

Would you provide us with some specifics that you presented in your session on managing itch in atopic dermatitis?

We discussed different mechanisms of targeting itch, targeting the narrow immune pathways, first targeting with type 2 cytokines, with the new drugs that target IL-4, IL-13, IL-31, and their pruritic effect. Beyond just atopic dermatitis and prurigo nodularis, we also discussed drugs that target narrow sensitization phenomena in the nerves, GABAergic drugs, and their doses, kappa opioids, as well as understanding the skin and brain mechanisms of itch.

What were some examples of the therapeutics you touched on during your presentation?

Specifically, we discussed in the biologic arena; Dupilumab, nemolizumab, and lebrikizumab as the major drugs, as well as a bit on drugs that are targeting the JAK-STAT pathway, abrocitinib and upadacitinib. We also discussed pregabalin and gabapentin, as well as the kappa opioids, [such as] butorphanol.

We’ve spoken before about chronic pruritus of unknown origin and your research related to this. Are there any updates that you'd want to share with colleagues?

 This is an entity that we see in our clinics, mainly in the elderly who have itch without a rash, or the rash is secondary to the scratching. It’s very common, and I would say that a lot of it was related to immunosenescence of type 2 cytokines overexpression, and therefore, drugs such as dupilumab and nemolizumab could work for these patients. With dupilumab, an ongoing study is being conducted, and hopefully, the phase 3 trials will be published this year or next year. Nemolizumab is also starting this type of drug trial, and I can tell you from my own clinical observation and off-label use, these drugs seem to be very promising for this condition.

Outside of atopic dermatitis and itch, are there any developments in dermatology you're looking forward to recently?

I think any chronic itchy condition is of interest to me in my research. I strongly believe that we need to better understand neuropathic itch and how to treat it. I've mentioned in my talk about the GABAergic drugs, but there are possibly other drugs that could target some of the narrow transmission of it. Whether these are Nav1.7, 1.8 inhibitors, or other drugs, and it could really target the nerve itself, rather than just the immune system, because in the neuropathic itch, the immune system has a minor role.

What do you see as the value of disease-specific conferences such as RAD?

 I like RAD, because I think that it emphasizes a lot of components of inflammation in the skin. Atopic dermatitis is a great hallmark condition where the inflammatory immune system works with nerves. Therefore, we can learn a lot from RAD to treat other conditions that involve inflammation of the skin.

For any additional information related to Yosipovitch’s presentation or related topics covered at RAD 2025, view our 

The quotes used in this Q&A interview were edited for the purposes of clarity.

Gil Yosipovitch, MD, discussed the management of pruritus in atopic dermatitis at the RAD Conference, focusing on targeting immune pathways and nerve sensitization. He highlighted biologics like Dupilumab, Nemolizumab, and Lebrikizumab, as well as JAK-STAT inhibitors, GABAergic drugs, and kappa opioids. Yosipovitch emphasized the potential of these treatments for chronic pruritus of unknown origin, particularly in the elderly. He also expressed interest in neuropathic itch research, advocating for a deeper understanding of nerve-targeting therapies beyond immune system modulation.

In this interview, Yosipovitch touches on the topics featured in his RAD 2025 presentation ‘Managing Itch,’ specifically regarding patients with atopic dermatitis. 

Managing Itch Among Patients with Atopic Dermatitis, with Gil Yosipovitch, MD

Gil Yosipovitch, MD

This year has been a whirlwind for patients seeking medical care and treatment. The impact of the 

 pandemic has taken its toll on patients, caregivers, healthcare professionals, and their families alike.

These challenges are intensified, however, when it comes to 

 and often catastrophic epilepsies that can be very difficult to treat, such as Dravet syndrome or Lennox-Gastaut syndrome (LGS), both of which are infant- and childhood-onset diseases. Not only is it critically important for these patients to receive a precise diagnosis as early as possible so that treatments can be tailored to achieve the best outcomes, it’s also crucial to ensure they receive timely ongoing care.

Families living with rare epilepsies will tell you how socially isolating these diseases are. Unpredictable and prolonged life-threatening seizures unfortunately are very common for these patients, who experience frequent medical emergencies, lifelong developmental and behavioral impairments, and an increased risk of death. 

As a result, even during the best of times, these patients’ families avoid everyday activities that could trigger seizures due to overexcitement, overheating, or exposure to illnesses like the common cold, in order to keep their loved one safe.

Imagine, then, how living under the shadow of COVID-19 has magnified the fears and concerns of these normally strong, resilient families, with many expressing increased feelings of depression and isolation. In the face of this pandemic, they are exercising extra caution and limiting patients’ visits even to clinics and emergency rooms to reduce the risks of contracting the novel coronavirus.

It’s important to reinforce for these families that hospitals and doctors’ offices are safe for both routine visits and emergencies. Fortunately, patients now have another safe option: telemedicine. What began as a pandemic necessity has become a powerful benefit. In fact, many epilepsy specialists are already providing the majority of their patients’ care though telemedicine. This dramatic shift has made it easier for health care providers, families, and patients to remain engaged with each other and to continue monitoring the patient’s individual treatment needs.

Telemedicine is helping the Dravet syndrome and other rare disease communities to keep medical appointments, investigate medications, enroll in clinical studies, and even start new treatments. Physicians also find telemedicine visits useful for detailed discussions about the risks and benefits of trying new anti-seizure medications that offer hope for improved seizure control and quality of life. Robust discussions can happen via telemedicine just as easily as they do during an in-person clinic visit.

With new medications recently approved specifically for some rare epilepsy syndromes, and healthcare providers learning more about their efficacy and side effects, treatment paradigms are evolving—suggesting that new levels of seizure control could become the standard for more Dravet syndrome and other rare epilepsy patients. Consultations via telemedicine help ensure caregivers have all the available information they need to make important decisions about their loved one’s care. In addition, physicians in healthcare systems and offices that use electronic medical records can deploy these systems to electronically prescribe new medications and order baseline laboratory or clinical assessments that may be needed.

Historically, both new and existing patients would be scheduled many months in advance for appointments. If a more urgent visit was needed, however, this was not always possible due to the availability of clinic space or caregiver and provider schedules not aligning. Now, a visit can be done via telehealth where an in-person physical exam is not necessary, allowing providers to “squeeze” in a 30-minute telehealth visit on a day when they ordinarily would not have had available time. This also saves families many hours of travel time, missed work, and having to potentially plan for the care of other family members and siblings. All these factors taken together have resulted in an increase in overall monthly visits for some epilepsy practices and the feedback from both patients and providers has been overwhelmingly positive.

Even with the pandemic, it’s important for families of rare epilepsy patients to continue to advocate for the best care possible, including referrals to specialists who may be more knowledgeable about specific rare epilepsies. Conferring with these specialists via telemedicine is another way that digital technologies are helping families keep up with the latest disease insights and treatment approaches during the pandemic. And for times when a second opinion may be needed, telemedicine provides ready access to the academic centers where many of these specialists practice, without the need to travel long distances.

Before the pandemic, our patient community had expressed interest in telemedicine as an alternative for in-person visits but have been frustrated with the lack of a set coverage standard with private health insurance providers. 

Patients with Dravet syndrome are prone to increased seizures during an illness. Being able to avoid in-person visits to hospitals or clinics for routine care during times of higher risk of infection, such as cold and flu season, would be optimal. And, since many of our patient families can travel hours to see their child’s specialists, being able to do some appointments via telemedicine takes away the additional financial burden caused by missed work and travel expenses.

Telemedicine gives families the added support and contact with healthcare providers that they need while navigating the challenges of rare disease care during unprecedented times. After the pandemic passes, many experts predict that telemedicine will remain as the new normal for many medical consultations—eliminating common barriers for patients, their families, and providers alike.

Joseph Sullivan, MD, is from the UCSF Benioff Children’s Hospital Pediatric Epilepsy Center of Excellence.

Mary Anne Meskis, is the Founding Member and Executive Director, Dravet Syndrome Foundation.

The views expressed in this piece reflect those of the authors, not necessarily those of the publication. 

Healthcare providers and experts interested in responding to this piece or being published on HCPLive can contact the staff

Families of patients with Dravet syndrome and other rare epileptic burdens have lived under amplified fear this year. That is why telemedicine is a more vital tool than ever.

Ensuring Continuity of Care for Rare, Catastrophic Forms of Epilepsy During COVID-19

Joseph Sullivan, MD, and Mary Anne Meskis

 In the start of early 2020 we did things different at Duke in our practice because patients weren’t afraid to change therapies or start new therapies or even continue their therapy. How has the pandemic affected you as far as keeping patients on drug and compliant, starting new medications and seeing them in clinic, and then tell us about your mix of video, telemed [telemedicine] to in person visits?

It’s been a challenging time. In the beginning, we had a lot of education for our patients to let them know that from the data we had from New York, places like NYU [New York University], Columbia, that it was safe to stay on medication. It was better to have inflammation controlled than your body trying to fight the disease and then trying to fight COVID-19. Once we got our patients educated enough on that fact, infusion went on as always. We didn’t miss a beat. If you weren’t coming in for an infusion, then we did a lot of video visits. They must come in at least every 6 months for a real appointment because you must touch patients. There’s no question. We can educate patients though and change medications on a video visit, I thought that was helpful. I’m glad that we had that option because it’s not safe to bring in people. Not everybody is vaccinated. With omicron especially patients are getting sick, even with 3 vaccines. We’re going to keep patients apart as much as possible, but patients are sticking with their medication because the data is out there, and we use evidence-based medicine and educate our patients and have good patients.

For the first 2 weeks of the pandemic, we were at home of course, just getting telemed [telemedicine] set up because we didn’t use it in our practice before the pandemic, which now I see was unfortunate. Once we got telemed running, I was 3 days in person in the office. We continued to see patients and they were coming in and then it was a wonderful day at home with telemed [telemedicine] up until June 1st, 2021. Duke [University] said, “OK, we’re all going back into clinic,” when we thought the numbers were going to go down and stay down. What I elected to do in June was I wanted to keep at least a half of day at clinic for my patients who are stable, and I could see them every 6 months in person but do some telemed [telemedicine]. Telemed [telemedicine] has become an important part of my practice and I will continue to utilize that. What percentage are you doing telemed [telemedicine] versus in-person visits?

Currently, the only people I’m letting in the office are people who need an injection or are coming in for infusions. Everybody else, because the numbers have been terrible, we have been doing video visits or phone visits if they can do a video just for the protection of our infusion patients and our other immunocompromised patients.

I will say that our infusion suite has been busy since the beginning of the pandemic. We’re fortunate to have individual bays and private rooms where the door slides and they’re soundproof and patients don’t have to worry about sharing germs, but we are just so backed up, continue to be backed up with infusions. So patients really were not afraid to come in during the pandemic to get their infusion. The same for you that you’ve experienced, right?

Yes. Once they were educated and knew that it was safer for them to be in control, we never missed a beat which is great. The only thing certain if somebody was getting a subq [subcutaneous injection] in the office we would go out to the car to make it more comfortable for a few of our medications that we use in psoriatic arthritis [PsA]. It’s a simple injection but other than that we try to keep patients as safe as possible. We don’t have the advantage of individual rooms. We have a big infusion suite. We had to decrease our number of chairs to give proper spacing, but we ran longer hours. We did everything we needed to do to make sure that everybody was accommodated.

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Before closing out their discussion on psoriatic arthritis management, two experts consider how the COVID-19 pandemic has affected their practice.

Managing PsA During the COVID-19 Pandemic

Michele M Cerra, MSN, FNP-C

In recent years, cell therapy has begun integrating into the clinical trial landscape for autoimmune diseases. The shift, which began with an early push in lupus, has since expanded into early programs in several indications, including myasthenia gravis, multiple sclerosis, systemic sclerosis, myositis, stiff person syndrome, and others.

Thus far, no cell therapies have been approved for treating autoimmune diseases – or even entered phase 3 trials for such indications – but nonetheless, the possibility of curative-type therapies has generated great excitement in the field. Chimeric antigen receptor (CAR) T-cell therapies, for example, are able to target and eliminate B-cells, and are thus a promising mode of treatment for B-cell-driven autoimmune diseases. Years of experience with CAR-T therapy in oncology and long-term data supporting its durability and efficacy are supporting the move into autoimmune disease.

Companies leading the charge to bring cell therapy to autoimmune disease include 

 one of the first companies to investigate CAR-T therapy for lupus; 

, all of which have cell therapies in phase 2 trials for autoimmune diseases. These programs have produced life-changing results in many patients and disappointing results in others. As a wide array of other companies have launched and continue to launch phase 1 trials, experts in the field have pointed out that while cell therapies may be curative for certain patients, they will certainly not be for all.

“[Cell therapy] generates an enormous amount of hype. Some of that is justified, but we have to see the long-term data. We’ve had similar levels of excitement in the past, and long-term data sort of tempered our expectations. I don't want to seem like a denier with this, but I think we just need to sort of take it in the context of where it is. It will probably be a very effective therapy for a small portion of treatment resistant patients. How much that's generalized across the disease, we'll see. But we'll get the answer eventually,” Jack Arnold, a clinical research fellow and clinician treating lupus at Leeds Centre of Rheumatic and Musculoskeletal Medicine told 

Supporting the move into autoimmune disease now are years of experience with CAR-T therapy in oncology and long-term data supporting its durability and efficacy. 

spoke with experts, advocates, and companies engaged in the cell therapy autoimmune scene to learn more about what the field learned from hematology/oncology, continuing progress in the field, and unlocking cell therapy’s full potential for autoimmune disease in the rheumatological field.

Lessons Learned With Cell Therapy for Autoimmune Disease

Lupus, including systemic lupus erythematosus (SLE) and lupus nephritis (LN), was one of the first areas of investigation for cell therapies such as CAR-T therapy. Lupus Research Alliance and its clinical affiliate Lupus Therapeutics have helped to bring a number of cell therapies to the clinical stage through its Lupus Clinical Investigators Network (LuCIN) and partnerships with companies making progress in this area including Bristol Myers Squibb, Cabaletta, Caribou Bio, Nkarta, and others.

 As such, they are a key player in the space with a unique view on cell therapy’s potential and progress for autoimmune diseases.

Stacie Bell, PhD, executive vice president of Lupus Therapeutics, sat down with 

 during the American College of Rheumatology (ACR) 2024 Convergence in November to discuss the changing field of autoimmune disease.

ACR Bell Video: This Year in Medicine

“When the first major publication came out in November 2022

, for CAR T and the involvement with the lupus community, it was like something I'd never thought I would ever see in my career, you know, to see people basically have complete disease remission, not only relief of symptoms, but actually their lived disease course,” Bell said.

Bell discussed the growth of investigations into cell therapy since their initial introduction and how groups such as Lupus Research Alliance, Lupus Therapeutics, and the FDA have worked together since then to facilitate research in the space. She emphasized the importance of taking learnings from oncological experience with cell therapy and translating them to the rheumatology field, as well as the importance of supporting patient education and informed consent.

“...Translating the love language between hematology and oncology and the things that they've experienced into the rheumatology community and how that relates to those living with autoimmune disease is an important element,” Bell said.

Bell also reminded viewers that no one therapy is 100% effective for everyone and cell therapy is no exception, although it has acted as a curative therapy for a number of patients with lupus in the follow-up done thus far.

Future Goals for CAR-T in Autoimmune Disease

Schett Cell Therapy Video: This Year in Medicine

The first-in-human clinical study of CAR-T in autoimmune disease began around 3 years ago. At the time, not much was known about the potential safety and efficacy of CAR-T in patients with autoimmune disease, and as such the trial was carried out in patients with severe disease who had generally exhausted other treatment in options. Notably, an autologous CAR-T product was used, with the standard lengthy manufacturing time for such products.

Since this and other early trials have shown some promising signs of long-term safety and efficacy, experts are now thinking about the next steps to optimize the safety, efficacy, and accessibility of CAR-T for autoimmune disease, as well as ways to broaden eligibility. In December 2024, CGTLive spoke with Georg Schett, MD, vice president of research and chair of internal medicine at the University of Erlangen – Nuremberg, who served as an investigator on the earliest CAR-T trial for autoimmune disease. Schett discussed what has been learned from these early efforts, pointing out that the risk of high grade cytokine release syndrome and neurotoxicity was shown to be low, thus suggesting a strong safety profile for the modality in autoimmune disease. Schett also discussed key areas of innovation that may be a focus of future clinical research for CAR-T in autoimmune disease. For example, he discussed the technically challenging process of manufacturing autologous CAR T-cells and the need to streamline and shorten this process in order to utilize fewer resources and less space. He also spoke about the potential of using hypoimmunogenic allogeneic CAR T-cells in order to further improve scalability and time-to-treatment. 

Schett also noted that if CAR-T in autoimmune disease continues to demonstrate safety, it may eventually be able to be used as an earlier-line treatment in patients with severe autoimmune disease. He emphasized the potential benefits of CAR-T over other options in this scenario.
“Imagine you can abrogate the whole disease with a single infusion and do this early and prevent organ damage,” Schett told CGTLive. “I think that concept is very appealing. At the moment, I think we are not there because [earlier on] data on safety were basically not present, but now [those data] are actually coming up more and more. So at the beginning, actually, the therapy was limited to very resistant patients, but I think the concept to move earlier, if safety data look good, which they do so far, is extremely appealing to prevent organ damage.”
Schett also touched on the fact that most CAR-T trials for autoimmune disease are still in phase 1, but that in the future more CAR-T products will be brought into phase 2 and phase 3 studies. Although, he highlighted that recruiting patients for CAR-T trials poses some unique challenges compared to other modalities, and that even phase 3 trials for CAR-T in autoimmune disease may continue to include relatively lower numbers of patients compared to more conventional treatments like antibody therapies.

The Role of Established Pharmaceutical Companies in Bringing Cell Therapy to Autoimmune Disease

Van Eickels Cell Therapy in Autoimmune Disease

The earliest efforts exploring the use of CAR-T in autoimmune disease were carried out by academic institutions and small biotech companies. As the technology has shown promise, however, more and more companies have begun to show interest in launching trials for CAR-T products in autoimmune disease. Among these are large, well-established pharmaceutical companies, with previous experience developing and commercializing CAR-T in oncology and substantial resources to dedicate to new research in autoimmune disease. One such company is Bristol Myers Squibb (BMS), which already has an FDA-approved CD19-directed CAR-T product for oncology indications and is now also exploring the potential of CD19-directed CAR-T in autoimmune diseases including lupus, systemic sclerosis, idiopathic inflammatory myopathies, and multiple sclerosis. CD19 NEX-T, the company’s lead CAR-T candidate for autoimmune disease, is currently being evaluated in 2 clinical trials, data from one of which were presented at the 2024 ACR Convergence.

In the lead up to the conference, CGTLive spoke with Daniela van Eickels, MD, PhD, MPH, the vice president and head of medical affairs for BMS’s Cell Therapy Organization, about the company's plans for developing CAR-T products in autoimmune disease. Notably, BMS has formed the Autoimmunity Cell Therapy Network (ACTioN) Steering Committee in order to foster collaboration and facilitate the advancement of investigational candidates.

“ACTioN is a BMS initiative where we are providing a platform that should enable deep connectivity and the building of a network between the different stakeholders that are involved in cellular therapies and how to bring them into the field of autoimmunity,” van Eickels 

. “We understand from our past that the patient journey will touch on different disciplines, and it is very important that this is a seamless connectivity along the patient journey.”

An important factor in the application of CAR-T to autoimmune disease has been the need for collaboration at the level of individuals between oncology specialists who have practical experience using CAR-T therapies in the clinic and autoimmune disease specialists who are disease area experts. Van Eickels also discussed more generally how this concept applies on the institutional level, as well.

“I think, generally speaking, we are very, very excited about the concept of deep immune reset,” van Eickels told CGTLive. “It's something that we are driving with utmost urgency, knowing that there are currently patients that are really suboptimally treated. We hope that by accelerating [this approach] we will really bring a real value to those patients. This is something that we really need to execute together with scientific experts, clinicians, and the patients that go on our studies. This is where we see the biggest value of an established player like BMS bringing that all together and also using our expertise in cellular therapies from other areas.”

Translating CAR-T Therapy from Oncology to Autoimmune Disease

Zachary Roberts NDA Plans ACR 2024

Another, smaller company that has begun to integrate rheumatological targets into an oncology-focused pipeline is Allogene Therapeutics, with its ALLO-329, an allogeneic CD19/CD70 dual CAR-T. Allogene presented preclinical data from the program at the ACR Convergence that demonstrated the therapy’s dual targeting and elimination of targeted B-cells in mouse models.

Zachary Roberts, MD, PhD, executive vice president of Research & Development and Chief Medical Officer of Allogene, spoke with HCPLive during the ACR Convergence and shared that the company plans to file an investigational new drug (IND) application for the therapy in early 2025. He also discussed Allogene’s experience developing cell therapies for oncology and now rheumatology.

“We are very good at dealing with toxicities that we expect to see with CAR-T,” Roberts said. “...We have direct clinical experience with that CAR molecule in patients with oncologic disease... we have encountered several of the same kind of toxicity profiles that others have seen with CD19 and BCMA CARTs. And so, we feel very prepared.”

Allogene’s pipeline is still comprised mostly of oncological allogeneic CAR-T therapies, with lead candidate cemacabtagene ansegedleucel currently in phase 2 trials for large B-cell lymphoma.

Roberts discussed how Allogene and other companies investigating CAR-T for autoimmune disease, most of which began their pipelines with oncologic indications, are able to take their experience developing, investigating, and managing CAR-T and its treatment in this new group of patients. Of course, there are many differences in patients with malignancies compared with autoimmune diseases, and approaches will need to be adapted and tailored to these patients.

“Rheumatologists are not oncologists, and autoimmune patients are not cancer patients. And so, you really have to come at this with a point of view that is tailored to the target audience... We plan to... further reduce the intensity of the lymphodepletion and ideally, we'll be able to get rid of it all together. So, this product design really was founded on this idea of tailoring this towards a group of physicians and a group of patients whose needs are different than oncologists and patients with malignant disease,” Roberts said.

Further commenting on the interplay between cell therapy for cancers and autoimmune diseases, Roberts mused that CAR-T's quick expansion in the rheumatological field feels the same as CAR-T's initial launch in the oncology field. He shared his excitement over what he believes will be an exciting new couple of years for the field.

The field of CAR-T for autoimmune disease has made substantial progress over the past few years. Following promising early results from academic institution-led clinical research in lupus, biotech companies began jumping into the race to bring CAR-T to autoimmune diseases beginning in late 2022, with a flurry of new trials being launched by companies from that point onward 

Now, in 2024, as this trend continues, and companies such as Cabaletta and Cartesian have begun to announce positive early efficacy and safety 

, some experts are beginning to think about the longer-term future.

The possibility of bringing CAR-T into earlier lines of treatment for autoimmune disease, the need to improve manufacturing processes, the potential of allogeneic approaches, and benefits of collaboration and knowledge-sharing across disciplines and would-be competitors are all relevant considerations on the horizon now. With that in mind, the need for vigilance and cautious optimism also remains, as the ultimate proportion of patients with autoimmune diseases who may actually stand to benefit from cell therapy continues to be uncertain. Regardless of how things play out, the field will likely need to make adjustments and accommodations as the landscape develops.

“We have the deep belief that this is a true innovation so it will require some adaptations in the healthcare environment,” van Eickels additionally told CGTLive. “We are trying to enable early conversations on what needs to change and what needs to happen, so that these new therapies can actually really benefit a wide array of patients if the data prove that to be beneficial.”

Mackensen, A., Müller, F., Mougiakakos, D. et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. 

28, 2124–2132 (2022). doi: 10.1038/s41591-022-02017-5

Current Collaborations and Initiatives. Lupus Therapeutics. 2024. Accessed December 24, 2024. https://lupustherapeutics.org/current-partner-studies/

Taking ACTioN. Bristol Myers Squibb. Website. Accessed December 24, 2024. 

https://www.bms.com/researchers-and-partners/areas-of-focus/our-research-in-immunology/taking-action.html

Allogene Therapeutics to Present Pre-Clinical Data Highlighting the Potential of ALLO-329, an Allogeneic CD19/CD70 Dual CAR T for the Treatment of Autoimmune Diseases, at the American College of Rheumatology (ACR) Convergence. Allogene Therapeutics. September 26, 2024. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-present-pre-clinical-data-highlighting

Cabaletta Bio presents positive clinical safety and efficacy data on CABA-201 at ACR Convergence 2024. News release. Cabaletta Bio, Inc. November 18, 2024. Accessed December 24, 2024. 

https://www.cabalettabio.com/news-media/press-releases/detail/119/cabaletta-bio-presents-positive-clinical-safety-and

Cartesian Therapeutics announces positive updated results from phase 2b trial of Descartes-08 in participants with myasthenia gravis and outlines design of planned phase 3 trial. News release. Cartesian Therapeutics, Inc. December 3, 2024. Accessed December 24, 2024. 

https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-positive-updated-results-phase

Cell therapy is emerging in clinical trials for autoimmune diseases, with CAR-T therapies showing promise, particularly in B-cell-driven conditions. Despite no approvals or phase 3 trials yet, the potential for curative treatments is generating excitement. Companies like Kyverna Therapeutics and Bristol Myers Squibb are leading phase 2 trials, though results vary. Experts emphasize the need for long-term data and caution against overhyping. Future goals include optimizing CAR-T safety, efficacy, and accessibility, with potential earlier-line use. Collaboration between oncology and autoimmune specialists is crucial for advancing these therapies.

Cell therapy, particularly CAR-T, is expanding into autoimmune diseases like lupus and multiple sclerosis. While promising, safety, efficacy, and broad applicability remain uncertain.

Leveling Up: Cell Therapy Research Expands Horizons in Autoimmune Disease

Noah Stansfield

Morello is a professor in the department of physiology & cell biology, orthopedic surgery, and pediatrics at the University of Arkansas for Medical Sciences.

I am a musculoskeletal researcher with an active interest in rare diseases, especially those caused by collagen alterations. Our disease of choice for the last 20 years has been 

 (brittle bone disease) that is most commonly caused by alterations in type I collagen. Its severity ranges from mild to lethal and it dramatically affects the skeleton by causing low bone mass and recurrent fractures after minimal trauma.

In addition to studying the impact of this disease on the skeleton, about 7 years ago—in collaboration with John L. Carroll, MD, a pulmonologist at Arkansas Children’s Hospital—we began looking into its impact on the lung and respiration. In fact, OI can cause severe respiratory distress at birth, and adult patients with OI often suffer from decreasing pulmonary function and are more vulnerable to diseases such as pneumonia.

The role of congenital collagen alterations during lung development and their effect on lung structure and function are not well understood. To study these important aspects, we elected to use a rare disease such as OI as the paradigm of a connective tissue disease with a primary alteration in type I collagen and as an entry point into a poorly addressed but medically relevant issue.

OI, caused by either dominant mutations in 

 genes or by loss of function of genes involved in type I collagen processing (e.g. 

) is the most common bone fragility disorder;

 however, respiratory distress at birth and a decline in respiratory function are leading causes of mortality in patients with OI.

 This is because type I collagen is expressed in most tissues and the disease is systemic, with skeletal and extra-skeletal manifestations that affect many organs, including the lung.

Therefore, there is a critical need to understand how type I collagen alterations negatively impact lung development and function with the goal to identify new therapeutic targets to improve the health of patients with OI.

We recently demonstrated that, similar to what happens in osteoblasts and skin fibroblasts, the production of type I collagen is also dysregulated in lung fibroblasts in the 

 We have now analyzed 3 distinct mouse models of OI and identified intrinsic lung defects consistent with early onset impairment of alveolar formation that led to significant alterations in respiratory function by 3 months of age.

 This contradicts the current model that predicts that the skeletal features of the OI disease, such as abnormalities of the chest wall and kyphoscoliosis are the only causes that prevent proper lung inflation leading to restrictive disease. Interestingly, mouse models mimicking a more severe type of OI showed more severe changes in their respiratory parameters.

The overall objective of this proposal is to gain adequate mechanistic understanding to dissect and separate the contribution of intrinsic developmental lung changes from those of extrinsic skeletal changes causing chest wall hypoplasia or defects. Our central hypothesis is that intrinsic lung changes contribute significantly to respiratory impairment in OI and result in cellular loss during the terminal morphogenetic process of alveolar formation.

We proposed to determine the consequences of type I collagen mutations in the lung independent from their effects on the skeleton, using a newly developed conditional knock-in mouse model for type I collagen (aim 1); we also proposed to identify cellular and molecular changes in the lung of CrtapKO compared to WT mice using single-cell RNA sequencing (aim 2).

The lack of a mouse model to study the effects of OI type I collagen mutations in a tissue-specific manner has prevented us to understand the primary impact of these mutations on the respiratory system because the skeletal changes caused by OI (in the thoracic cage, vertebral column, ribs, and/or diaphragm) can significantly affect lung function. To overcome this long-standing limitation, we generated a new mouse model where a classic glycine substitution (p.G1146R) in the triple helical region of type I collagen can be expressed in specific cells/tissue using a mouse Cre-recombinase driver strain. We crossed this new mouse model with a transgenic mouse expressing Cre in all tissues and confirmed that the offspring carrying both the new allele (

) and the Cre-recombinase reproduced all features of a severe form of OI, including low bone mass and fractures but also severe alveolar simplification in the distal lung parenchyma together with alterations in several respiratory mechanic parameters.

 glycine substitution just in the lung (using a Tbx4-Cre mouse strain), a maneuver that leaves the skeleton intact, our data indicated that the parenchyma morphology of the lung was mostly intact and several of the respiratory mechanics parameters were normal and undistinguishable from the control mice, unlike what we observed when expressing the mutation globally. However, both the K parameter (measuring the concavity of the descending limb of the PV curve) and V10_TLC (the lung volume at 10 cmH20 expressed as a percentage of the total lung capacity) were still significantly reduced in 

These data indicate that the expression of the G1146R mutation in the lung only causes a milder phenotype. However, the significantly reduced K and V10_TLC parameters indicate intrinsic lung changes consistent perhaps with potential fibrosis and/or surfactant alterations.

Collectively, our data suggest that skeletal defects in OI play a major impact on respiratory function of OI patients. However, it is important to remember that type I collagen is also expressed in the diaphragm and the pleural membranes and its alterations in these structures may also significantly contribute to altered lung development/function in OI.

We are also pursuing studies to determine cellular and gene expression changes in a recessive mouse model of OI (

 mice). We have currently performed 2 independent experiments using single-cell RNA sequencing on WT and 

 5-week-old mice, and plan to perform a third one soon. We are observing changes in fibroblast cell populations in the lung and the third experiment will be useful to determine whether such changes also impact alveolar epithelial cells.

The analysis of these data is still ongoing, and we will also hopefully delineate transcriptional changes affecting the critical process of alveologenesis. Thanks to the American Lung Association support, we have now secured additional funding from the National Institutes of Health (NIH) to pursue and further expand these studies using spatial transcriptomics.

Newborns diagnosed with a skeletal dysplasia, including OI, frequently suffer from respiratory problems that result in prolonged and expensive hospital stays in pediatric intensive care units with limited therapeutic options. These patients offer unique challenges for the physician due to the complex care they require. It is our hope that our studies will lead to a better understanding of the role of type I collagen in alveologenesis and provide new therapeutic targets for improved lung disease management in patients with OI.

Marini, J.C., Forlino, A., Bachinger, H.P., Bishop, N.J., Byers, P.H., Paepe, A., Fassier, F., Fratzl-Zelman, N., Kozloff, K.M., Krakow, D., et al. 2017. Osteogenesis imperfecta. 

Jovanovic, M., and Marini, J.C. 2024. Update on the Genetics of Osteogenesis Imperfecta. 

Folkestad, L., Hald, J.D., Canudas-Romo, V., Gram, J., Hermann, A.P., Langdahl, B., Abrahamsen, B., and Brixen, K. 2016. Mortality and Causes of Death in Patients With Osteogenesis Imperfecta: A Register-Based Nationwide Cohort Study. 

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Dimori, M., Heard-Lipsmeyer, M.E., Byrum, S.D., Mackintosh, S.G., Kurten, R.C., Carroll, J.L., and Morello, R. 2020. Respiratory defects in the CrtapKO mouse model of osteogenesis imperfecta. 

American journal of physiology. Lung cellular and molecular physiology

Dimori, M., Fett, J., Leikin, S., Otsuru, S., Thostenson, J.D., Carroll, J.L., and Morello, R. 2022. Distinct type I collagen alterations cause intrinsic lung and respiratory defects of variable severity in mouse models of osteogenesis imperfecta. 

Better known as brittle bone disease, osteogenesis imperfecta can cause severe respiratory distress at birth and longterm effect to respiratory function. Morello shares his team's research into the cause of this effect.

Elucidating the Role of Type I Collagen Mutations on Respiratory Function in Osteogenesis Imperfecta

Roy Morello, PhD

Sobia Laique, MD, is a gastroenterologist and transplant hepatologist at Cleveland Clinic.

Metabolic Surgery’s Benefit for MASH-Related Cirrhosis, with Soba Laique, MD

Resmetirom (Rezdiffra) made history in 2024 when it became the first therapeutic to earn US Food and Drug Administration approval for the treatment of 

metabolic dysfunction-associated steatohepatitis (MASH)

Although the approval represented a major breakthrough for the field of hepatology and offered a long-awaited pharmacologic treatment option for many affected patients, it did not address the unmet needs of all MASH patients. Indicated specifically for those with noncirrhotic MASH and moderate to advanced fibrosis, resmetirom’s approval did not include patients with MASH-related cirrhosis, a population that still does not have an FDA-approved treatment.

In the absence of medical therapies, recent research has focused on other interventions to help improve outcomes for these patients. Designed to examine the long-term association between metabolic surgery and the risk of progression to major adverse liver outcomes (MALO), the Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) study enrolled patients with compensated biopsy-proven MASH-related cirrhosis and compared outcomes between metabolic surgery and medical management.

“What our findings revealed was a 72% lower risk of incident MALOs and an 80% lower risk of hepatic decompensation in the surgical group, which are staggering numbers to see,” Sobia Laique, MD, a gastroenterologist and transplant hepatologist at Cleveland Clinic, explained in an interview with 

She went on to describe the “substantial” clinical impact of this research, highlighting evidence of a reduced risk of cirrhosis progression with metabolic surgery and the potential implications of these findings for liver transplant eligibility in patients who eventually reach decompensated cirrhosis but otherwise may not have been eligible for transplant due to their weight.

“As physicians, we're always trying to push boundaries and find the next best thing to help our patients,” Laique said.

Looking ahead to research she would like to see conducted in the future, Laique highlighted the need for studies assessing the safety and efficacy of metabolic surgery in patients with severe obesity who have cirrhosis and clinically significant portal hypertension; studies comparing medical therapies with surgical weight loss; and studies exploring metabolic surgery’s potential impact on cirrhosis regression.

Laique reviews data supporting the use of metabolic surgery in patients with obesity and cirrhotic MASH.

Authors