Can Gene Editing Be A 'Functional Cure' For Sickle Cell Disease?

may come in the form of an experimental one-time gene editing cell therapy, renizgamglogene autogedtemcel (reni-cel), according to findings published in the 

Reni-cel is designed to modify a patient’s own blood-forming stem cells to correct the mutation responsible for sickle cell disease, increasing fetal hemoglobin levels to prevent red blood cells from forming into sickle-shaped cells, and improving overall hemoglobin levels to reduce complications from the disease.

nephrology team spoke with the lead author and chair of the Pediatric Hematology – Oncology & Blood and Bone Marrow Transplant Division at Cleveland Clinic Children’s, Rabi Hanna, MD, for his perspective on the results from the RUBY trial.

What Are We Missing In Sickle Cell Disease Treatment?

Previous gaps in the common treatment options for sickle cell disease include limited donor availability and the possibility of graft-versus-host disease.

“Gene therapy is autologous, so every patient can essentially donate to themselves. And because it is autologous, you don’t usually have graft rejection or graft-versus-host disease, so no immunosuppression is required.”

data on burnout rates in physicians who treat sickle cell disease at 60%

, partially attributed to structural barriers in patient care.

Gene Editing Sickle Cell Disease With Reni-cel

In the phase 1-2 multicenter open-label, single-group study, study investigators evaluated reni-cel, an investigational clustered regularly interspaced short palindromic repeats (CRISPR)–Cas12a gene-edited autologous hematopoietic stem-cell therapy.

“Reni-cel is a novel therapy and represents a different approach. It is still autologous, but the gene-editing technique differs from previously approved therapies in two key ways. First, it uses Cas12a instead of Cas9, which offers greater specificity,” explained Hanna.

“The more important distinction is that it mimics a natural process. Approved gene therapies typically target BCL11A binding, whereas this approach targets the HBG1 and HBG2 promoters—similar to what occurs in individuals with sickle cell disease who remain asymptomatic due to persistently elevated fetal hemoglobin. We examined the underlying mutation in those individuals and aimed to replicate it. That is the rationale behind this study: to evaluate the safety and efficacy of this approach.”

Patients were treated with a single infusion of renicel after myeloblative conditioning with busulfan, a high-dose chemotherapy regimen used before allogeneic stem cell transplantation (HCT) to eliminate cancer cells and suppress the immune system.

The trial included 28 patients with severe sickle cell disease who were 12 to 50 years of age with ≥2 severe vasco-oclusive events per year in the previous 2 years.

According to the results, among 27 patients who had neutrophil and platelet engraftment by the data-cutoff date, neutrophil engraftment, the process where transplanted stem cells begin producing new, healthy blood cells in a patient's bone marrow. occurred after a median of 23 days (range, 14 to 29). Additionally, platelet engraftment, the process where newly transplanted stem cells begin producing platelets, signaling recovery in hematopoietic stem cell transplants, occurred after a median of 25 days (range, 17 to 51).

At month 6, among 18 patients with at least 6 months of available data, the mean (±SD) total hemoglobin level (9.8±1.7 g per deciliter at baseline) had increased to 13.8±1.9 g per deciliter, and the mean percentage of fetal hemoglobin (2.5±2.5% at baseline) had increased to 48.1±3.2%. Both of these measures remained stable.

In terms of pain crisis, 1 patient had 2 severe vaso-occlusive events after infusion. Overall, the adverse events were consistent with those that occur after myeloablative busulfan-based conditioning and autologous hematopoietic stem-cell transplantation.

Stay up to date with the rest of our conversation with Hanna to learn more about the significance of the reduction in pain crisis for patients with sickle cell disease. 

Editor’s Note: Hanna reports relevant disclosures with Chiesi USA, Inc., Swedish Orphan Biovitrum AB (Sobi), and Vertex Pharmaceuticals Incorporated. 

Hanna R, Frangoul H, Pineiro L, et al. CRISPR-Cas12a Gene Editing of 

 Promoters to Treat Sickle Cell Disease. 

Popat UR, Pasvolsky O, Bassett Jr. R, et al. Myeloablative fractionated busulfan for allogeneic stem cell transplant in older patients or patients with comorbidities. 

https://doi.org/10.1182/bloodadvances.2023010850

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Hanna, MD, shares results from reni-cel, a one-time gene editing therapy for patients with sickle cell disease. 

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Strategic Alliance Partnership

Vinod E. Nambudiri, MD, MBA, MPH, is affiliated with Brigham and Women's Hospital and specializes in Dermatology and Internal Medicine.

How the AAD Clinical Image Collection Can Help Dermatologists, With Vinod Nambudiri, MD, MBA, MPH

2026 American Academy of Dermatology (AAD) Annual Meeting

 brought forward a timely and clinically relevant discussion with Vinod Nambudiri, MD, MBA, MPH, of Brigham and Women’s Hospital, centered on advancing dermatologic care for diverse patient populations. The conversation highlighted both the progress made and the ongoing gaps in addressing conditions that disproportionately affect individuals with skin of color, with a particular emphasis on health equity, access to care, and emerging therapeutic strategies.

A central theme of Nambudiri’s discussion was the importance of recognizing how dermatologic diseases can present differently across skin tones, and how these variations can contribute to delayed diagnosis or misdiagnosis. The speakers emphasized that improving clinician education remains critical, particularly in ensuring that providers are trained to identify subtle or atypical presentations in darker skin types. This gap in training continues to be a barrier to optimal care and underscores the need for more inclusive educational resources and clinical imagery.

The conversation also explored the psychosocial burden of dermatologic conditions in patients with skin of color, noting that visible skin diseases often carry significant stigma. This burden can be further compounded by cultural perceptions, societal pressures, and disparities in access to specialized care. As such, Nambudiri stressed the importance of culturally competent care and shared decision-making, ensuring that treatment plans align with patient preferences, expectations, and lived experiences.

Emerging therapies and innovations were another focal point, particularly in the context of conditions such as pigmentary disorders, inflammatory diseases, and hair disorders that are more prevalent or uniquely impactful in these populations. While new treatments are expanding the therapeutic landscape, the discussion underscored that clinical trial diversity remains insufficient. Increasing representation of patients with skin of color in research was identified as essential for generating data that are both generalizable and clinically meaningful.

In addition to therapeutic advancements, Nambudiri highlighted the role of community engagement and advocacy in driving change. Efforts to improve outreach, patient education, and trust in the healthcare system were noted as key components in addressing longstanding disparities. The integration of patient voices into both research and clinical practice was also emphasized as a means of ensuring more equitable and effective care delivery.

Overall, the discussion reflected a growing momentum within dermatology to prioritize inclusivity and equity. While meaningful strides have been made, the speakers acknowledged that sustained efforts are needed across education, research, and clinical practice to fully address disparities and improve outcomes for patients with skin of color.

Editor’s note: This summary was developed with the help of AI tools.

Nambudiri discusses the AAD Clinical Image Collection, launched in January 2025 to address the lack of diverse representation in dermatology education.


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Abigail Brooks is an assistant managing editor for 

She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

Although Wilson disease is considered a rare condition, clinicians at a recent HCPLive clinical forum convened by Lance Stein, MD, transplant hepatologist and the medical director of Piedmont’s Hepatology and Liver Transplant Program, emphasized that its true burden may be underestimated due to frequent delays and missed diagnoses. The discussion brought together hepatologists to examine real-world challenges in recognizing and managing the disease, with a focus on diagnostic uncertainty, treatment strategies, and long-term care.

Participants noted that many clinicians encounter only a handful of cases throughout their careers, contributing to limited familiarity and variability in practice. Even among specialists, experience is often based on a small number of patients, underscoring the importance of shared clinical insights and case-based learning.

A central theme of the discussion was the highly variable presentation of Wilson disease. Caused by mutations in the ATP7B gene leading to impaired copper metabolism, the disease can manifest across a wide clinical spectrum, including hepatic, neurologic, and psychiatric symptoms.

Panelists emphasized that this heterogeneity frequently complicates diagnosis. Patients may present with nonspecific liver abnormalities that resemble more common conditions such as fatty liver disease or autoimmune hepatitis, particularly in younger individuals. Others may present primarily with neurologic or psychiatric symptoms, sometimes without any overt liver disease, making recognition even more difficult.

In some cases, diagnosis is made only after significant disease progression, including cirrhosis or acute liver failure. Clinicians shared experiences of patients who were diagnosed late in the disease course and, in some cases, even after liver transplantation, highlighting the consequences of delayed recognition.

Despite established diagnostic tools, identifying Wilson disease remains challenging in practice. Forum participants discussed the limitations of commonly used tests, including ceruloplasmin levels, which may be normal in certain clinical contexts or misleading in acute illness.

As a result, clinicians often rely on a combination of tests, including 24-hour urinary copper excretion and, increasingly, genetic testing. However, even these approaches can yield ambiguous results, particularly in patients with atypical presentations or discordant findings.

Panelists emphasized the importance of maintaining a high index of suspicion, especially in younger patients with unexplained liver disease or atypical clinical features. Several noted that misdiagnosis or delayed diagnosis is common, particularly when symptoms overlap with more prevalent conditions or when extrahepatic manifestations predominate.

Once diagnosed, management of Wilson disease centers on reducing copper accumulation through chelation therapy or blocking copper absorption. Chelating agents such as D-penicillamine and trientine are commonly used to promote copper excretion, while zinc therapy may be used to reduce intestinal absorption, particularly in maintenance settings.

Treatment selection often depends on disease severity and clinical presentation. In acute or severe cases, particularly those involving liver failure, more aggressive therapy is required. Liver transplantation remains a definitive treatment option in patients with acute liver failure or decompensated cirrhosis and is unique in that it effectively corrects the underlying metabolic defect.

However, panelists noted that treatment comes with its own set of challenges. Rapid copper removal during chelation can sometimes worsen neurologic symptoms, requiring careful titration and monitoring. Additionally, psychiatric manifestations may persist even after treatment, further complicating management decisions.

Beyond initial treatment, long-term management of Wilson disease presents additional hurdles. Lifelong therapy is required to maintain copper balance, and adherence can be difficult, particularly in younger patients or those with psychiatric comorbidities.

Clinicians highlighted real-world challenges such as medication tolerability, access, and lifestyle factors that may affect adherence. Treatment regimens may need to be adjusted over time, including transitions between chelators and maintenance therapies such as zinc.

Family screening was also emphasized as a critical component of care, given the genetic nature of the disease. Early identification of affected individuals can allow for timely intervention before the onset of significant organ damage.

Looking Ahead: Opportunities for Improvement

The forum discussion underscored that while effective treatments for Wilson disease exist, improving outcomes will depend on earlier recognition and more consistent application of diagnostic strategies.

Participants highlighted the need for increased awareness across specialties, particularly among clinicians who may encounter atypical presentations, including neurologists and psychiatrists. Greater use of genetic testing and improved diagnostic algorithms may also help reduce delays.

Ultimately, the discussion reflected both the progress and the ongoing challenges in managing this rare but potentially life-threatening disease. For clinicians, maintaining vigilance and leveraging a multidisciplinary approach may be key to improving detection and long-term outcomes in Wilson disease.

Wilson Disease Association. Wilson Disease. Published August 13, 2021. Accessed April 16, 2026. 

https://wilsondisease.org/do-i-have-wilson-disease/?gad_source=1&gad_campaignid=16684019432&gbraid=0AAAAADN9hfNH0Qklo1N7KKX3qO0womQLJ&gclid=CjwKCAiAw9vIBhBBEiwAraSATuJdNxoP57_7zjL0DUUF0B9EceR3whBrdSIFmutmQSsj2E3BL4nQkhoC-xwQAvD_BwE

NIDDK. Diagnosis of Wilson Disease. October 2018. Accessed April 16, 2026. 

https://www.niddk.nih.gov/health-information/liver-disease/wilson-disease/diagnosis

Articles

Wilson disease remains underrecognized despite effective therapies, largely due to protean hepatic, neurologic, and psychiatric presentations and limited clinician exposure. Diagnostic delay is common when nonspecific liver abnormalities mimic MASLD or autoimmune hepatitis, or when extrahepatic symptoms predominate. Standard tests such as ceruloplasmin can mislead, necessitating multimodal evaluation with urinary copper and genetic testing. Management requires individualized chelation or zinc strategies, careful monitoring for neurologic worsening, and attention to adherence barriers. Family screening and multidisciplinary care are pivotal.

Experts discuss diagnostic challenges, variable presentations, and strategies to improve outcomes in Wilson disease.

Hepatology

From Diagnosis to Management: Addressing Gaps in Wilson Disease Care

Ryan Livingston joined the MJH Life Sciences team in March of 2025, shortly after graduating from TCNJ with a bachelor’s degree in English. He enjoys creative writing, reading, and scuba diving. He can be reached at rlivingston@mjhlifesciences.com.

Thomas Seck, MD | Image Credit: Fierce Healthcare

Eli Lilly’s orforglipron (Foundayo) has proven its noninferiority to insulin glargine in adults with 

 or overweight at increased cardiovascular risk, according to topline results from the ACHIEVE-4 trial.

Orforglipron, a once-daily small molecule non-peptide oral GLP-1 receptor agonist, is able to be taken at any time of day without any restriction on food or water intake. It was 

on April 1, 2026, receiving an indication for adults with overweight or obesity and related conditions.

“Across 7 phase 3 studies enrolling more than 11,000 patients, Foundayo has demonstrated a consistent safety and efficacy profile,” Thomas Seck, MD, senior vice president of product development at Lilly Cardiometabolic Health, said in a statement. “ACHIEVE-4 adds a new dimension to that evidence – cardiovascular safety and a lower observed risk of all-cause death in patients who carry elevated cardiovascular risk.”

ACHIEVE-4 was the largest and longest study of orforglipron in T2D to date, including >2700 patients across 15 countries. Patients were eligible for inclusion if they presented with a diagnosis of T2D and an increased risk of cardiovascular disease events due to coronary heart disease, cerebrovascular disease, or congestive heart failure, among other criteria. Patients were excluded from the trial if they had 

, chronic or acute pancreatitis prior to screening, a known clinically significant gastric emptying abnormality, acute or chronic hepatitis, or any other liver disease, among other criteria.

Eligible patients were randomly assigned to receive either orforglipron or insulin glargine. Orforglipron was administered in escalated oral doses, while insulin glargine was administered subcutaneously in individualized doses which were titrated according to a treat-to-target algorithm. The study’s primary outcome was time to first occurrence of any major adverse cardiovascular event (MACE), including myocardial infarction, stroke, hospitalization for unstable angina, and cardiovascular death. Secondary outcomes included change from baseline in HbA1c, fasting serum glucose, and body weight, among others.

Ultimately, orforglipron met its primary endpoint, demonstrating a 16% lower risk of the primary MACE endpoint compared to insulin glargine (HR, 0.84; 95% CI, 0.59-1.2), meeting the prespecified criteria for non-inferiority (upper limit of 95% CI of the HR <1.8). Additionally, all-cause death risk was 57% lower with orforglipron (HR, 0.43; 95% CI, 0.25-0.75; nominal 

 = .002). Orforglipron also demonstrated clinically meaningful improvements from baseline in non-HDL-C, systolic blood pressure, triglycerides, and hsCRP.

Investigators also noted a safety and tolerability profile consistent with that of previous trials and with the GLP-1 class as a whole. The most common adverse events were nausea, vomiting, diarrhea, constipation, and decreased appetite. 10.6% of patients in the orforglipron arm discontinued treatment during the 52-week minimum treatment period.

“Together with the simplicity of a once-daily pill that requires no food or water restrictions, we believe Foundayo could be an important new treatment option for people with type 2 diabetes,” Seck said.

In the release, Lilly announced its plan to submit orforglipron for the treatment of T2D to the FDA by the end of Q2 2026, using the Commissioner’s National Priority Review Voucher.

Eli Lilly. ACHIEVE-4, the longest Phase 3 study of Lilly’s Foundayo (orforglipron) to date, reaffirmed its cardiovascular and overall safety profile as well as consistent improvements across key measures of cardiometabolic health. April 16, 2026. Accessed April 16, 2026. 

https://investor.lilly.com/news-releases/news-release-details/achieve-4-longest-phase-3-study-lillys-foundayo-orforglipron

Eli Lilly. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions. April 1, 2026. Accessed April 16, 2026. 

https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-foundayotm-orforglipron-only-glp-1-pill

Eli Lilly and Company. A Study of Daily Oral Orforglipron (LY3502970) Compared With Insulin Glargine in Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk (ACHIEVE-4). ClinicalTrials.gov Identifier: NCT05803421. Updated January 21, 2026. Accessed April 16, 2026. 

https://clinicaltrials.gov/study/NCT05803421

Lilly’s oral small-molecule GLP-1 receptor agonist orforglipron (Foundayo) achieved cardiovascular noninferiority versus insulin glargine in high–cardiovascular-risk adults with type 2 diabetes and overweight/obesity in ACHIEVE-4, the largest and longest T2D study for the agent. The primary MACE endpoint favored orforglipron (HR 0.84; 95% CI 0.59–1.20) and all-cause mortality was lower (HR 0.43; nominal P=.002). Metabolic risk markers improved, and tolerability aligned with class GI effects, with 10.6% discontinuation.

Results from the largest and longest trial of orforglipron to date have displayed the drug’s efficacy in reducing all-cause cardiovascular death and MACE incidence.

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Type 2 Diabetes

ACHIEVE-4: Orforglipron Non-Inferior to Insulin Glargine for Cardiovascular Protection in T2D

Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease

This episode, titled 'Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease,' features panelists discussing the standard and evolving protocols for identifying Wilson disease in various patient populations. Dr. Rima Fawaz explains that while elevated alanine aminotransferase (ALT) remains the most common signal for a pediatric workup, the medical community is entering a new era shaped by preconception genetic testing and advanced screening. The discussion highlights a pilot neonatal screening program in Washington state that measures ATP7B protein peptides. Although this testing offers the potential to catch patients before they become symptomatic, the experts note current limitations, including false positives and the need for more robust data.

The conversation also addresses how age influences the clinical profile of the disease. While younger children primarily present with hepatic symptoms, neurological manifestations such as tremors and hyperkinetic movements typically emerge in pre-teen years or young adulthood. Dr. Peter Hedera notes that as patients age, they may trend toward hypokinetic movements, though the disease remains highly heterogeneous.

To differentiate Wilson disease from other movement disorders like Parkinson’s, the panel emphasizes a multi-modal diagnostic approach. Because clinical signs alone are often nonspecific, experts rely on a suite of confirmatory tests, including ceruloplasmin levels, 24-hour urine copper, and non-ceruloplasmin copper (NCC) assays. They also discuss the utility of neuroimaging for detecting T2 signal changes in the basal ganglia and the importance of ophthalmological exams to identify Kayser-Fleischer rings. The episode concludes by reinforcing that because Wilson disease is such a persistent masquerader, clinicians must maintain a low threshold for laboratory evaluation to avoid missing a diagnosis.

In the next episode, 'Multidisciplinary Collaboration and Diagnostic Frameworks in Wilson Disease,' panelists will continue their discussion on Wilson disease and highlight the importance of a team-based approach involving hepatologists, neurologists, and psychiatrists. The conversation covers the practical application of the Leipzig score and the growing role of next-generation sequencing in identifying preclinical cases.

Learn how subtle liver enzyme changes and age-specific movement symptoms signal Wilson disease, plus the latest on newborn screening and tests.

Video Series

Psoriasis care shifts beyond skin: treat-to-target goals, heart risk reduction, and new oral TYK2 pills with strong safety data.

Zasocitinib in Plaque Psoriasis from the LATITUDE Trials

Clinicians across specialties spot red flags, refer early to GI, and follow guidelines to improve diagnosis and management.

Who Diagnoses EPI? Defining Roles Across the Care Team

Wilson disease mimics tremor, dystonia, Parkinsonism or psychosis; watch for subtle liver signs and screen early to avoid delay.

Understanding Pathophysiology and Copper Transport in Wilson Disease

Discover how oral TYK2 inhibitors deliver targeted psoriasis control with strong safety data and biologic-like clearance, including insights on deucravacitinib and zasocitinib.

The Role of TYK2 Inhibitors in Modern Psoriasis Care

Why EPI stays missed: barriers to enzyme therapy, targeted fecal elastase testing, and preventing malnutrition, bone loss, and QoL decline.

EPI Unmet Needs: Barriers to Diagnosis and Long-Term Consequences

Martina J. Porter, MD, is a dermatologist at Beth Israel Deaconess Medical Center.

Extension data through week 54 reveal deepening responses with povorcitinib in moderate-to-severe HS.


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Povorcitinib Efficacy Holds in Biologic-Experienced HS, With Martina Porter, MD

Thierry Passeron, MD, PhD, is a professor and chair of the Department of Dermatology at the Université Côte d'Azur in Nice, France.

This Q&A interview highlights several takeaways from the data on upadacitinib in patients with non-segmental vitiligo (NSV).

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Key Insights on Upadacitinib’s Efficacy for Non-Segmental Vitiligo, With Thierry Passeron, MD, PhD

Chelsie Derman is an associate editor for 

who covers allergy and  psychiatry. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

Evidence from 3 recent studies explores microbiome modulation, early allergen exposure, and immune tolerance as pathways for food allergy prevention.

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Can Food Allergy Be Prevented Before It Begins? A Look At 3 Recent Studies

Clinicians discuss diagnostic gaps, treatment strategies, and multidisciplinary care in Wilson disease.

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HS is associated with up to a nearly 2-fold increased risk of heart failure, coronary artery disease, myocardial infarction, venous thromboembolism, and all-cause mortality.

Latest News

Can Gene Editing Be A 'Functional Cure' For Sickle Cell Disease?

How the AAD Clinical Image Collection Can Help Dermatologists, With Vinod Nambudiri, MD, MBA, MPH

From Diagnosis to Management: Addressing Gaps in Wilson Disease Care

ACHIEVE-4: Orforglipron Non-Inferior to Insulin Glargine for Cardiovascular Protection in T2D

Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease