Tag: Medication

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Acute Myeloid Leukemia Therapy Improved by CRISPR Stem Cell Transplant

For highly aggressive types of blood cancer, stem cell transplantation is often the only potentially curative therapy. Yet, these cancers can often return even after a transplant. Notably, CAR T cell therapy has not been effective against all blood cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

A recent Phase I/II multicenter clinical trial, led by researchers at Washington University School of Medicine in St. Louis, shows that a stem cell transplant, that removes CD33 from donor cells using CRISPR, can help prevent cancer recurrence.

The work was published in Nature Medicine and titled, “CRISPR−Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a Phase I/II trial.” The study was conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, and 14 other sites in the U.S. and Canada. 30 adult patients with AML or MDS at high risk of relapse received the stem cell transplant.

Myeloid cancers, such as AML and MDS, are difficult to treat with CAR T cells because the same proteins targets are present on both cancer cells and healthy myeloid cells, leading to toxicity risks.

“We are encouraged by the results of this study showing that a CD33-deleted stem cell transplant looks very similar to the outcomes of standard stem cell transplantation,” said John DiPersio, MD, PhD, professor of medicine at WashU Medicine and corresponding author of the study. “In the future, we are hopeful we will be able to combine this with CD33-targeted immunotherapies, such as CAR T cells, and improve treatment options for patients with these very aggressive blood cancers.”

As proof of concept, patients also received a maintenance therapy that targets CD33, after completion of the stem cell transplant. While not a CD33-targeted CAR T cell, the maintenance therapy, called gemtuzumab ozogamicin, is an engineered antibody that targets CD33 and carries an anti-cancer drug. Gemtuzumab ozogamicin is approved by the Food and Drug Administration (FDA) to treat CD33-positive AML and is in clinical trials for CD33-positive MDS. While it helps prevent relapse, the drug’s use is limited because it can cause liver toxicity and damage to blood cells, including dangerously low counts of white blood cells, red blood cells, and platelets.

All patients from the trial achieved engraftment of their transplanted stem cells by day 28. Some patients met this goal sooner with platelet production returning by day 16 on average. These timeframes are comparable to those of standard transplanted stem cells.

Average survival was just over 14 months. Nineteen patients received at least one cycle of the antibody maintenance therapy as part of a dose-escalation protocol. The authors found that patients maintained blood cell counts across all doses, suggesting that the gene-edited stem cell transplant protected patients from low blood cell counts typically seen following a standard stem cell transplant.

DiPersio and colleagues published a single case study detailing a patient with high-risk AML who received a CD33-deleted stem cell transplant. Upon relapse after the transplant, the patient received a CD33-targeted CAR T cell therapy, which used T cells from the same donor who provided the stem cell transplant.

The treatment resulted in complete remission and the patient remains cancer free over one year after receiving the CAR T cell therapy. Normal blood cell production returned with all blood cells lacking CD33, providing evidence that the genetically engineered donor cells had established themselves in the bone marrow.

DiPersio said the results of the study lay the groundwork for developing paired CD33-deleted stem cell transplant and CD33-targeted immunotherapy interventions that avoid destruction of healthy donor cells in the course of cancer treatment.

The post Acute Myeloid Leukemia Therapy Improved by CRISPR Stem Cell Transplant appeared first on GEN – Genetic Engineering and Biotechnology News.

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Antibody Promotes Nerve Regeneration in Spinal Cord Injury Patients

Swiss research shows treatment with an antibody known as NG101 promotes regeneration of damaged spinal cord tissue in some people with spinal cord injury by blocking a protein called Nogo-A that normally suppresses nerve regrowth in the central nervous system.

Compared to placebo, participants treated with the antibody showed faster lesion volume shrinkage and a significantly slower loss of spinal cord tissue, both in terms of size and myelin content, above the injury site.

This study, published in Nature Communications, is an additional analysis of a subset of 106 patients of a Phase IIb study published last year in The Lancet Neurology and carried out by Swiss and German academic researchers as well as the Swiss biotech NovaGo Therapeutics, which is developing the antibody. The original trial population included 126 people.  It did not robustly meet its primary endpoint across the full patient population but showed promising signals in some motor-incomplete patients.

The current study specifically looked at people for whom magnetic resonance imaging (MRI) data were available. It investigated whether NG101 produced measurable structural changes in the spinal cord over time, whether MRI could detect those changes even in patients without obvious clinical improvement, also whether combining imaging with electrophysiology could better identify likely responders to inform more efficient future trial designs.

In the Phase IIb study the antibody was delivered directly into the spinal canal to 106 participants with acute cervical spinal cord injury within weeks of injury. Over a six month follow up period, the team measured lesion volume, spinal cord cross-sectional area, and myelin integrity.

The patients treated with NG101 showed a slowing of damage and faster injury improvement than those in the placebo group. The researchers believe this suggests the drug either slows post-injury neurodegeneration or actively promotes nerve fiber sprouting.

“Our data suggest that NG101 antibody treatment demonstrates both focal and remote structural preservation following cervical spinal cord injury, consistent with regenerative mechanisms seen in preclinical models,” write lead author Patrick Freund, MD, PhD, a professor and researcher at the University of Zurich and Balgrist University Hospital, and colleagues.

“These changes are detectable even in participants without overt functional improvement, underscoring the value of quantitative MRI in revealing treatment effects that may be missed by clinical scores alone.”

The post Antibody Promotes Nerve Regeneration in Spinal Cord Injury Patients appeared first on Inside Precision Medicine.

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Single Procedure Reduces Colorectal Cancer Risk Decades Later

A single screening procedure could reduce the risk of colorectal cancer for decades, Norwegian trial findings indicate.

Once-only flexible sigmoidoscopy to screen for CRC and remove precancerous lesions provided sustained benefits, according to 23-year follow up of the Norwegian Colorectal Cancer Prevention (NORCCAP) trial.

Men experienced a far greater reduction in CRC incidence than women with the procedure, which involves using a thin, flexible tube to view the lower part of the large bowel.

Their risk of death relating to the cancer also decreased by a third, with no significant survival benefits for women.

“Our findings suggest that a single flexible sigmoidoscopy can have a long-lasting effect on CRC incidence and death,” reported Edoardo Botteri, PhD, from the Norwegian Institute of Public Health in Oslo in the Annals of Internal Medicine.

CRC is the third most common cancer worldwide and, while several screening tests are available, there is not enough evidence to recommend one over another.

As a result, many countries use fecal immunochemical testing (FIT) for CRC screening, whereas others use endoscopic screening with colonoscopy or sigmoidoscopy.

To investigate the potential benefits of sigmoidoscopy further, the team randomly assigned Norwegians aged between 50 and 64 year and living in the city of Oslo or Telemark county to either a once-only sigmoidoscopy examination or usual care without screening in a 1:3 ratio.

Participants invited for flexible sigmoidoscopy were further randomly assigned to either bring or not to bring three successive stool samples for fecal blood testing on attending their sigmoidoscopy procedure.

Those with positive screening results—involving any polyp at least 10 cm, any adenoma, CRC, or positive FIT result—were referred for colonoscopy within six weeks. Adherence to colonoscopy after a positive sigmoidoscopy result was 96%.

Overall, 100,210 persons were randomly assigned to a group, and 98,654 were included in intention-to-screen analyses.

This included 20,552 individuals in the screening group and 78,102 in the no-screening group. Participation with screening was 61.4% in men and 64.7% in women.

In men, the 23-year cumulative risk for CRC was 4.3% with screening and 6.0% without, while in women the corresponding risks were 4.2% and 4.7%.

In men, the 23-year cumulative risk for CRC death was 1.4% in the screening group and 2.2% in the no-screening group, while for women this was 1.3% and 1.4%, respectively.

The effect was strongest for rectosigmoid cancer. Adding fecal blood testing to sigmoidoscopy did not change the benefits of screening.

“Our findings indicate that among men screening was associated with an approximately 28% reduction in CRC incidence and a 37% reduction in CRC death over long-term follow-up, corresponding to absolute risk reductions of 1.7 and 0.8 percentage points, respectively,” the researchers reported.

“In women, screening was associated with a more modest relative risk reduction in CRC incidence (11%; absolute reduction, 0.5 percentage points), with no corresponding reduction in CRC death.”

The post Single Procedure Reduces Colorectal Cancer Risk Decades Later appeared first on Inside Precision Medicine.

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First Clinical Trial for a GLP-1 Gene Therapy Greenlit in Europe

Fractyl Health has received regulatory approval in the Netherlands to start the first-ever clinical trial for a gene therapy to treat type 2 diabetes. The upcoming Phase I/II clinical trial will test the safety and preliminary efficacy of RJVA-001, a gene therapy designed to locally deliver GLP-1 receptor agonist drugs with the goal of reducing the side effects associated with oral administration. 

“GLP-1 medicines have changed what is possible in obesity and type 2 diabetes, but they require chronic, high-dose systemic exposure that many patients cannot or do not sustain,” said Harith Rajagopalan, MD, PhD, co-founder and CEO of Fractyl Health. “RJVA-001 takes a different path: a potential one-time, pancreas-targeted gene therapy designed to enable the body to produce GLP-1 in response to meals: physiology, not pharmacology.” 

Based in Burlington, Massachusetts, Fractyl Health develops novel approaches to treating obesity and type 2 diabetes. The company’s lead program, an endoscopic procedure to maintain weight loss after discontinuing GLP-1 treatment for obesity, is currently being evaluated in a pivotal clinical trial. 

RJVA-001 leverages an engineered version of the human insulin promoter to trigger the production of GLP-1 in pancreatic beta cells when glucose levels rise after eating. The gene therapy is delivered using a minimally invasive endoscopic infusion directly into the pancreas, which is guided by ultrasound. 

The Phase I/II study will evaluate the safety, tolerability, and preliminary efficacy of three escalating doses of the gene therapy. Participants will include adults with type 2 diabetes who have previously responded well to oral GLP-1 treatment yet continue to experience difficulties controlling their blood sugar levels. 

“With this authorization, RJVA-001 becomes the first AAV gene therapy candidate to enter clinical development for type 2 diabetes,” said Rajagopalan. “We expect to dose the first patient and report initial data in the second half of 2026.”

Later this year, Fractyl expects to expand the study to additional sites in Australia, where the company has already submitted a clinical trial application and is currently awaiting a response from regulators. 

RJVA-001 will be the first candidate from Fractyl’s Rejuva platform to enter clinical development. This smart GLP-1 gene therapy platform focuses on the development of next-generation adeno-associated virus (AAV)-based gene therapies that are locally delivered to the pancreas. Another candidate developed through this platform includes a dual GIP/GLP-1 gene therapy to treat obesity, currently in preclinical development.  

“For decades, we have managed [type 2 diabetes] as a chronic, progressive disease that inevitably worsens over time. With this authorization, we are preparing to test, for the first time in humans, whether a one-time, pancreas-targeted gene therapy delivered via a routine endoscopic procedure could provide durable metabolic control by enabling physiologic, nutrient-responsive GLP-1 expression at the source of disease,” said Jacques Bergman, MD, PhD, professor of gastrointestinal endoscopy and deputy chair of the department of gastroenterology and hepatology at Amsterdam UMC, and a principal investigator of the upcoming clinical trial. 

“Patients who remain inadequately controlled despite maximally tolerated GLP-1 receptor agonists and multiple oral agents represent a population with significant unmet need. If successful, RJVA-001 could transform how we think about [type 2 diabetes], from a chronic disease you manage every day to one that could potentially be treated once.”

The post First Clinical Trial for a GLP-1 Gene Therapy Greenlit in Europe appeared first on Inside Precision Medicine.

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Supreme Court extends mifepristone deadline

Get your daily dose of health and medicine every weekday with STAT’s free newsletter Morning Rounds. Sign up here.

Good morning. My co-workers and pals Isabella Cueto and Lev Facher have been talking about alcohol for years. As STAT’s reporters on chronic disease and addiction, respectively, it’s right at the intersection of their beats, yet rarely covered as a public health issue. I’m happy to share that all their talking turned to reporting, and now an incredible series. The first parts are up now. Scroll down or skip ahead to start reading. 

Read the rest…

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Substance P–expressing neurons in the hypothalamic paraventricular nucleus mediate chronic cough hypersensitivity via the hypothalamus–airway neural pathway

Background and purposeIncreased cough sensitivity is the key pathophysiological mechanism of chronic cough. Although previous studies have focused on peripheral airway receptor sensitization, the role of the central nervous system—particularly the hypothalamic paraventricular nucleus (PVN)—remains unclear. Whether substance P (SP)–expressing PVN neurons contribute to cough hypersensitivity remains unknown.MethodsThree-week-old Hartley guinea pigs were divided into three groups: citric acid (CA), saline control (SA), and blank control (CON). A cough hypersensitivity model was induced by inhalation of 0.4 mol/L citric acid. Cough sensitivity was assessed using a capsaicin challenge, with the C5 threshold defined as the lowest capsaicin concentration inducing ≥5 coughs. Locomotor activity was evaluated using the open-field test. Airway inflammation and goblet cell hyperplasia were examined by HE and PAS staining. SP and c-Fos expression in the PVN were detected by immunofluorescence and Western blot. HSV retrograde tracing was used to analyze the PVN-airway neural pathway associated with cough hypersensitivity.ResultsCompared with the control groups, guinea pigs in the CA group exhibited a time-dependent increase in cough frequency and enhanced cough sensitivity, as indicated by a reduction in the C5 threshold. Histological analysis revealed increased inflammatory cell infiltration and goblet cell hyperplasia in the airways of the CA group. SP and c-Fos expression, along with the proportion of SP/Fos double-labeled neurons in the PVN, were significantly increased in the CA group (all P < 0.05). Viral tracing confirmed the presence of HSV-positive neurons in the PVN, supporting a neural connection between the PVN and the airways.ConclusionActivation of SP-expressing neurons in the PVN is associated with cough hypersensitivity and suggests the presence of a potential PVN–airway neural pathway. These findings provide a theoretical basis for the development of central-targeted therapies for chronic cough.
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CRISPR−Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial

Nature Medicine, Published online: 12 May 2026; doi:10.1038/s41591-026-04362-1

In a first-in-human trial combining the transplantation of CD33-negative CRISPR-edited hematopoietic cells with the CD33-targeted antibody–drug conjugate gemtuzumab ozogamicin, all transplanted patients achieved primary engraftment, and the treatment was well tolerated.