galectin-1

FROM ACF EQUITY RESEARCH HEALTHCARE TEAM NASDAQ: BCLI READ ACF EQUITY RESEARCH'S INITIATION NOTE HERE READ ACF EQUITY RESEARCH'S RELATED THEMATIC RESEARCH NOTE ON REGENERATIVE MEDICINE – NEURODEGENERATIVE DISEASE STEM CELLS & ALS/MND/LOU GEHRIG'S HERE LONDON, June 14, 2024 /PRNewswire/ -- INITIATION NOTE: BrainStorm Cell Therapeutics Inc. (Nasdaq: BCLI) is focused on developing autologous mesenchymal stem cell (MSC) therapies for the treatment of neurodegenerative diseases (NDDs) – BCLI's primary target is the fatal amyotrophic lateral sclerosis (ALS/MND/Lou Gehrig's). Post hoc analysis of BCLI's PIII trial data shows BCLI's NurOwn® (debamestrocel, MSC-NTF), has statistically significant clinical effects on early-stage ALS sufferers and that placebo trialists deteriorate faster. Peer reviewed research (Mar 2024) indicated that BCLI's NurOwn® has a positive impact on NfL biomarkers for ALS. These and other factors have persuaded the FDA to sign up to the SPA binding commitment for a NurOwn® PIIIb ALS trial. BCLI has regained regulatory minimum value NASDAQ compliance. Our valuation captures only the smaller by patients US market and excludes the larger EU/UK market. Post hoc analysis of BCLI's PIII early stage (mild-moderate) ALS sufferers (baseline ALSFRS-R scores >=35) treated with BCLI's NurOwn® (debamestrocel, MSC-NTF) revealed positive clinical responses with respect to slowing of ALS disease progression (primary endpoint). However the PIII trial cohort consisted (unexpectedly) of 23% advanced ALS sufferers, clouding the primary and secondary end point statistical analysis (possible floor effects). The new PIIIb trial is designed to recruit a cohort of participants with ALSFRS-R scores >=35. Additionally, more recent peer reviewed research found that certain biomarkers involved in ALS pathology, specifically NfL, LAP and Galectin-1 were found to be predictive of positive clinical outcomes in NurOwn® (debamestrocel, MSC-NTF),-treated participants. If the new trial design is successfully executed, as we forecast, we expect a strongly positive valuation inflection point for BCLI. ALS: High Unmet Medical Need Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder (NDD) that affects motor nerve cells in the brain and the spinal cord. There are an estimated ~450k ALS patients worldwide (30k US and 51k European). Median survival post diagnosis is 2 to 5 years. Current treatment options have very limited efficacy. Tofersen addresses just 2% of ALS sufferers. There is a high unmet need to slow/reverse ALS progression. SUBSCRIBE TO ACF EQUITY RESEARCH to receive notifications of new research products and services for investors. Visit our website to find out more. DISCLOSURES: ACF Equity Research has received cleared funds in advance for a minimum one year service directly from the issuer, from an exchange, from a portfolio manager; from an investor group or and from an investor relations firm. ACF Equity Research has received for any of investment/equity/credit/ESG/sustainability research a fixed paid in full in advance annual fee in the range US$35,000 to US$75,000 service package dependent. SOURCE ACF Equity Research

The protein galectin-1 (Gal-1) has been identified as a new PET imaging biomarker for immune checkpoint blockade (ICB) therapy, allowing physicians to predict the tumor responses before beginning treatment. Information garnered from Gal-1 PET imaging could also be used to facilitate patient stratification and optimize immunotherapy, enabling targeted interventions and improving patient outcomes. The protein galectin-1 (Gal-1) has been identified as a new PET imaging biomarker for immune checkpoint blockade (ICB) therapy, allowing physicians to predict the tumor responses before beginning treatment. Information garnered from Gal-1 PET imaging could also be used to facilitate patient stratification and optimize immunotherapy, enabling targeted interventions and improving patient outcomes. This research was published in the May issue of The Journal of Nuclear Medicine. Immunotherapies, such as ICB, have produced promising clinical outcomes in melanoma, non-small cell lung cancer, and several other types of tumors. However, only a subgroup of patients experiences positive outcomes with objective response rates spanning between five and 60 percent. "Developing reliable approaches for assessing responses and selecting eligible patients for immunotherapy remains challenging," said Zhaofei Liu, PhD, Boya Distinguished Professor at Peking University in Beijing, China. "Current clinical criteria for monitoring solid tumor responses to immunotherapy are based on CT and MRI scans, but these methods result in a considerable delay between treatment commencement and response evaluation. Molecular imaging techniques, especially PET, have emerged as robust tools for predicting immunotherapy effectiveness through the real-time, quantitative, and noninvasive assessment of biomarkers in vivo." In the study, a mouse model was utilized to identify new imaging biomarkers for tumor responses to ICB therapy. Through a proteomic analysis (separation, identification, and quantification of proteins in a tumor), researchers found that tumors exhibiting low Gal-1 expression responded positively to ICB therapy. Next, Gal-1 was labeled with 124I and the radiotracer (124I-α-Gal-1) and small animal PET imaging and biodistribution studies were conducted to assess the specificity of the radiotracer. PET imaging with 124I-αGal-1 showed the immunosuppressive status of the tumor microenvironment, thus enabling the prediction of ICB resistance in advance of treatment. For tumors that were not predicted to respond well to ICB therapy, researchers developed a rescue strategy that utilized a Gal-1 inhibitor that significantly improved the chance for success. "Gal-1 PET opens avenues for the early prediction of ICB efficacy before treatment initiation and facilitates the precision design of combinational regimes," noted Liu. "This sensitive approach has the potential to achieve individualized precision treatment for patients in the future." This research was published online in March 2024.

Scientists have created a new zebrafish xenograft platform to screen for novel treatments for an aggressive brain tumor called glioblastoma, according to a new study. Glioblastoma is an aggressive and difficult-to-treat brain tumor in adults. On average, patients survive for only 1.5 years. The standard of care treatment for this disease, which includes surgery followed by radiation and chemotherapy, has not changed in 18 years. That's partly because the cancer is highly variable with many differences across the patient population. Secondly, these cancer cells also deceive the body in insidious ways: they even recruit immune cells called macrophages to help them. And thirdly, they are out of reach for most anti-cancer drugs, which have only a limited capacity to penetrate brain tissues. Besides the standard of care treatment, oncologists try out drugs on glioblastoma patients without any guarantee they'll work, often involving adverse side effects. "These patients really are in need of new therapies," says Professor Holger Gerhardt, the senior author of the study and vice-Scientific Director of the Max Delbrück Center in Berlin. "It is very important to identify the patients who do respond to a specific treatment, and the ones who do not." Lise Finotto, the lead author and a cancer researcher at the VIB-KU Leuven Center for Cancer Biology in Belgium and formerly at the Max Delbrück Center, and her senior collaborators Gerhardt and Professor Frederik De Smet at KU Leuven, have created a screening platform that could be refined to find novel targets for drugs against glioblastoma. It could also be used to check if a particular patient will respond to a therapy. The study was published in "EMBO Molecular Medicine." To understand how macrophages can interact with glioblastoma cells of different patients, the researchers created zebrafish "avatars." Gerhardt's lab works extensively with zebrafish. These three-centimeter-long fish are considered good model organisms as their embryos are translucent, making it possible to monitor what's happening inside. An unexpected survival Finotto investigated glioblastoma stem cells from seven patients collected by scientists at the De Smet lab, which is establishing a living tissue bank of glioblastoma samples. She injected them into zebrafish embryos, creating xenograft models -- an avatar for each specific patient. When she live-imaged the embryos, it appeared that the glioblastoma cells had adapted well to their new environment. She saw the zebrafish's immune system sending macrophages as part of an immune response to control the tumor. But as is typical in glioblastoma, the macrophages were suppressed. The tumors have several mechanisms to reprogram the macrophages so they help them grow. "We wanted to learn how to revert the macrophages to a tumor-attacking state," Finotto says. And a clue surfaced when they noticed that the tumor of one patient did not suppress the normal macrophage response. "Upon closer investigation of the medical details, we discovered that this patient was what we call a 'long-term survivor'," says De Smet at KU Leuven. "It's a term used for glioblastoma patients with a survival of more than five years, which is exceptionally rare in this brain cancer." Testing platform Their curiosity about the patient became the driving force behind the project, Finotto says. When they cultured the tumor cells and macrophages together and did single-cell RNA sequencing, they learned that one gene, LGALS1, was downregulated in the tumor of the long-term survivor compared to the others. Earlier studies have also shown that silencing of LGALS1 in glioblastoma cells can result in longer survival. The scientists confirmed their results by knocking out the gene in another patient's sample and observed in the zebrafish models that the tumor became less invasive. This platform could be used to identify promising targets other than LGALS1 for the treatment of glioblastoma, Finotto says. And with some refinement, zebrafish avatars could be used to identify which treatments will work. Researchers could investigate whether the tumor cells from particular patients grafted into zebrafish respond when treated with various drugs to find the ones that lead to tumor regression, Gerhardt says. "Armed with this information, we could inform oncologist and help them to make more supported treatment decisions for the patient," De Smet says.