Optic Neuropathy, Ischemic

Data replicate and expand upon the potential of ER-100 to improve retinal ganglion cell function and restore visual function in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (NAION)BOSTON, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Life Biosciences (“Life Bio”), a biotechnology company advancing innovative cellular rejuvenation technologies to reverse diseases of aging and injury and ultimately restore health for patients, today announced new data presented at the 2024 American Association of Ophthalmology (AAO) Annual Meeting that took place in Chicago, Illinois from October 18-21, 2024. Results replicate previously reported nonhuman primate (NHP) data and further expand our knowledge on dosing and timing of treatment. ER-100, a novel partial epigenetic reprogramming gene therapy containing Oct-4, Sox-2 and Klf-4 (OSK), was administered via a single intravitreal injection along with daily systemic doxycycline to NHPs with a NAION-like injury. Immunohistochemistry confirmed expression of each transcription factor (Oct-4, Sox-2 and Klf-4) in discrete cells in the perifoveal regions in ER-100 treated NHPs relative to vehicle. Furthermore, ER-100 significantly reduced deficits in pattern electroretinogram and axon density measures when administered in both prevention and rescue paradigms. Collectively, these results demonstrate that ER-100 successfully targets retinal ganglion cells and reduces the loss of visual function in an NHP model of NAION. Life Bio remains on track to initiate the first human clinical study evaluating ER-100 for optic neuropathies in the second half of 2025. “Partial epigenetic reprogramming has the potential to restore visual function for those with optic neuropathies such as NAION and glaucoma,” said Sharon Rosenzweig-Lipson, Ph.D., Chief Scientific Officer of Life Bio. “The data shared today replicate and build upon our understanding of the dosing of ER-100 and the timing of the treatment window relative to the onset of NAION-related damage. We look forward to advancing this program toward human clinical trials next year for patients affected by these age-related optic neuropathies.” About Life Biosciences Life Biosciences is a biotechnology company advancing innovative cellular rejuvenation platforms to reverse diseases of aging and injury and ultimately restore health for patients. The company is focusing on two platforms targeting key mechanisms underlying aging biology, epigenetic reprogramming and chaperone-mediated autophagy, to restore cells to a more youthful state. Therapies developed within these platforms have the potential to prevent, treat, and/or reverse multiple aging-related diseases. For more information, please visit www.lifebiosciences.com or follow us on Twitter and LinkedIn. Media Contact Kristin Politi, Ph.D.LifeSci Communicationskpoliti@lifescicomms.com(646) 876-4783

As a globally acclaimed medication, semaglutide has been making waves with its exceptional therapeutic effects. Not only has it demonstrated remarkable performance in diabetes treatment, but it has also successfully expanded its reach to areas like weight management, cardiovascular diseases, and kidney disorders.   Recently, JAMA Oncology, a subsidiary journal of the American Medical Association, published a compelling study that unveiled the potential of GLP-1 drugs like Ozempic and Wegovy to lower the risk of up to 10 types of cancer. This finding undoubtedly brings a new glimmer of hope to the field of cancer prevention.   The logic behind GLP-1 drugs' ability to reduce the risk of malignant cancers is not overly complex. It is well-known that overweight or obese individuals have a higher risk of developing cancer, and this risk further increases with the rise in body weight and the prolonged duration of being overweight. Semaglutide, through its unique mechanism of delaying gastric emptying, suppressing appetite, and enhancing feelings of satiety and fullness, helps patients achieve weight loss.   According to data from the Centers for Disease Control and Prevention (CDC), being overweight is closely linked to a series of physiological changes, such as chronic inflammation and abnormal elevations in insulin, insulin-like growth factors, and sex hormones, all of which are potential cancer-promoting factors. The CDC also points out that around 40% of new cancer diagnoses are associated with being overweight, with 13 types of human malignant tumors already established as obesity-related.   Recent analysis of a large electronic health record (EHR) dataset by researchers at Case Western Reserve University in the United States has yielded an exciting conclusion. They found that among patients with type 2 diabetes receiving GLP-1 drug treatment, the risk of developing 10 out of the 13 mentioned malignant cancers was significantly lower compared to those solely receiving insulin therapy. This discovery encompasses a wide range of common cancer types, including esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.   Interestingly, while the risks of breast cancer, thyroid cancer, and gastric cancer did not show statistically significant differences, the study revealed that GLP-1 therapy may help reduce the risk of postmenopausal breast cancer. This finding is particularly noteworthy, as postmenopausal breast cancer is one of the cancer types most closely linked to obesity.   However, semaglutide is not without its flaws. Although it can lower the risk of various malignant cancers, it may also increase the risk of certain cancers. For instance, compared to diabetic patients taking metformin, those using GLP-1 drugs may face a higher risk of kidney cancer. Furthermore, based on research findings and previous reports about insulin promoting cancer growth, GLP-1 injections may be associated with an increased risk of thyroid cancer.   Recent studies on the side effects of GLP-1 drugs have also sparked controversies around semaglutide. One study suggests that the use of Novo Nordisk's semaglutide injection may increase the risk of a rare eye disease called non-arteritic anterior ischemic optic neuropathy (NAION), a serious eye condition that can lead to blindness. The data shows that the probability of developing NAION is four times higher in patients with type 2 diabetes using semaglutide compared to those not using the drug.   Additionally, injecting semaglutide can trigger a series of gastrointestinal symptoms, such as nausea, diarrhea, vomiting, constipation, abdominal pain, bloating, and indigestion. These issues not only impact the patient's quality of life but may also have negative effects on the treatment's efficacy.   On social media, the "Ozempic Face" phenomenon has also garnered widespread attention. This refers to the physical changes, such as sunken cheeks, loose skin, and sunken eyes, that occur due to rapid weight loss after semaglutide injection. These changes have raised doubts about semaglutide's "beauty-enhancing" effects. In fact, semaglutide may potentially lead to muscle loss and functional decline, which is a limitation in its weight-loss applications.   In conclusion, while semaglutide holds potential value in cancer prevention for high-risk populations, for those seeking weight loss, a combination of dietary modification and exercise may be a more stable and effective approach. As we enjoy the benefits of semaglutide, we must also remain vigilant about its potential side effects and risks.

Harvard University researchers launched a single-center study after noticing incidents of nonarteritic anterior ischemic optic neuropathy among semaglutide users in clinical practice. Novo Nordisk’s massively successful GLP-1 analog semaglutide, the active ingredient in the popular diabetes and obesity meds Ozempic and Wegovy, may be linked to a vision loss disorder, a new study suggests. But one team of analysts cautioned against reading too much into the analysis. The study found that people taking semaglutide were four to nearly eight times more likely to develop nonarteritic anterior ischemic optic neuropathy (NAION) than their peers on other non-GLP-1 meds for diabetes and weight loss. The study was conducted by researchers at Harvard University and published last week in JAMA Ophthalmology. NAION is an eye condition that’s marked by decreased blood supply to the optic nerve, causing vision loss. It’s the second most common form of optic nerve damage, with an annual incidence rate estimated at around 2.3 to 10.2 per 100,000 among people over 50 years of age in the U.S., according to the American Academy of Ophthalmology. The study raises questions, but a Leerink Partners team led by David Risinger said in a Thursday note that they “do not expect this single analysis to impact prescribing trends” of Ozempic and Wegovy. That’s because, as the study authors themselves noted, the analysis was designed to report an “association” but not to establish a causal relationship. “Larger retrospective studies, post-marketing analyses of GLP-1s, and/or prospective clinical trials would be required to confirm the findings,” the analysts wrote. The Harvard researchers launched the study after noticing cases of NAION among semaglutide takers in clinical practice. So they evaluated nearly 17,000 patients seen by neuro-ophthalmologists at Massachusetts Eye and Ear between December 2017 and November 2023. Patients who were taking either Ozempic or Wegovy were matched with non-takers by various baseline characteristics, including comorbidities related to NAION. Among 710 patients with Type 2 diabetes, the cumulative NAION incidence over a 36-month period was 8.9% for users of semaglutide compared with 1.8% in the non-GLP-1 cohort. Among 979 individuals who were overweight or obese, the 36-month rates were 6.7% and 0.8% for the users of Novo’s med and other non-GLP-1 treatments, respectively. As the authors noted, Massachusetts Eye and Ear clinic includes a specialized neuro-ophthalmology service that evaluates a large proportion of the Boston area’s NAION cases. “[T]herefore, our findings may not be fully generalizable to other settings,” they wrote in the study. The best approaches to confirm the findings, the researchers noted, would be to conduct a much larger retrospective, multicenter population-based study, a prospectively designed randomized clinical trial or a postmarket analysis of all GLP-1 receptor agonists. But large studies may be difficult to run, because there isn’t a specific diagnostic code for NAION, the authors said. For this study, the researchers manually reviewed records and found that 40% of cases marked as ischemic optic neuropathy, the closest code relevant to NAION, were actually not NAION. NAION is currently not listed as a side effect in the labels of Ozempic or Wegovy. The increasing use of GLP-1 meds has spurred multiple population-based studies exploring their potential risks and benefits. Previous anecdotal reports of suicidal thoughts related to the use of semaglutide were recently refuted by a large Nature Medicine study involving 1.8 million patients. The FDA and the European Medicines Agency later found no association between the Novo drug and suicidal thoughts or actions. Other studies appeared to link the GLP-1 med to some unexpected benefits. A new JAMA Network Open study published on Friday involving 1.6 million patients with Type 2 diabetes found that compared with insulin, GLP-1 meds were associated with a significant risk reduction in 10 obesity-related cancers, including gallbladder cancer, liver cancer, ovarian cancer and colorectal cancer. In that same study, GLP-1 drugs were not associated with a decreased risk of any of the 13 cancers examined when compared with metformin but, instead, an increased risk of kidney cancer. Meanwhile, Novo Nordisk and its GLP-1 rival Eli Lilly have been busy confirming their offerings’ efficacy in various conditions beyond diabetes and weight loss. Lilly’s GIP/GLP-1 dual agonist Zepbound recently aced a phase 3 study in obese patients with obstructive sleep apnea. Novo’s semaglutide has also shown a benefit in slowing kidney disease progression in diabetic patients with chronic kidney disease. And Wegovy earlier this year secured an FDA approval to reduce the risk of cardiovascular-related events in patients who are overweight or obese with cardiovascular disease.