Latest news with #ALSP
Medscape
13 hours ago
- Health
- Medscape
Brain Cell Transplant Slows Rare Neurodegenerative Disease
Replacing mutant microglia with healthy donor-derived microglia has emerged as a promising treatment for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). In a small study of eight patients with ALSP, replacing dysfunctional microglia with normal microglia using traditional bone marrow transplantation (BMT) halted the progression of ALSP and improved neurologic function. 'The critical next step is to validate these results in a larger clinical trial, which is already underway,' principal investigator Bo Peng, PhD, professor, Institute for Translational Brain Research, Fudan University in Shanghai, told Medscape Medical News . The study was published online on July 10 in Science . From Mice to Men ALSP is a rare, progressive neurological disease with an average age of onset of 43 years and an average life expectancy of only 3-5 years after symptoms begin. There is no cure and there are few treatments. ALSP is caused by mutations in the colony-stimulating factor 1 receptor gene (CSF1R), which is critical to development and survival of microglia. Mutations in this gene lead to microglial dysfunction and reduced numbers of these key brain immune cells. In earlier work, Peng and his team developed mouse models of ALSP which exhibit hallmark features of the disease including reduced numbers of microglia, myelin abnormalities, axonal swelling and motor impairments, and cognitive decline. To test whether microglial replacement could alter disease progression in mice with ALSP, the investigators tested two approaches: traditional BMT and microglia replacement by BMT (Mr BMT), a protocol that combines pharmacological depletion of microglia with traditional BMT. Both approaches effectively replaced mutant microglia with wild-type counterparts and successfully reversed myelin defects, axonal swellings, and motor and cognitive impairments in the animals. To translate this to the clinic, they performed traditional BMT in eight patients with ALSP. Although traditional BMT alone typically does not achieve efficient Mr in healthy brains, the inherent CSF1R deficiency in patients with ALSP creates a 'competitive disadvantage' for the recipient's resident microglia, allowing traditional BMT to achieve effective replacement, the researchers explained in their paper. In the 2 years following Mr, MRI and clinical evaluations indicated 'halted disease progression, preserved motor function, and stabilized cognitive abilities,' the team reported. By contrast, untreated patients with ALSP exhibited rapid worsening of brain pathology over a shorter time frame. The findings in these eight patients also provide a 'mechanistic explanation' for a prior clinical case in which an individual with ALSP, initially misdiagnosed with adult-onset metachromatic leukodystrophy, exhibited long-term stabilization after traditional BMT. 'While the path forward is active with the ongoing trial, traditional BMT becoming a widely accessible 'clinic-ready' standard treatment for ALSP is still estimated to be several years away, contingent upon successful trial outcomes, long-term safety data, and subsequent regulatory approvals,' Peng told Medscape Medical News . Beyond ALSP Peng also said Mr 'holds significant theoretical promise' for treating other neurological diseases involving microglial dysfunction, including Alzheimer's disease (AD). 'Genome-wide association studies have identified TREM2 as one of the major risk genes in sporadic AD. TREM2 mutation may cause or accelerate the progression of AD. In a 2020 paper in Cell Reports , we proposed that we can replace the TREM2 -mutated microglia with TREM2 -normal cells to treat this disease,' Peng added. In a Science perspective , Siling Du, PhD, and Jonathan Kipnis, PhD, with the Brain Immunology and Glia Center, Washington University in St Louis congratulated Peng and colleagues for demonstrating in humans that 'correcting a microglial gene defect through cell replacement can arrest disease progression.' Du and Kipnis agreed that the potential implications of this research extend beyond ALSP. For example, a recent study demonstrated that microglial replacement can also rescue pathology in a mouse model of Krabbe disease, a monogenic neurodegenerative disorder caused by mutations in the gene encoding galactosylceramidase. In addition, traditional BMT has also been shown to arrest disease progression in a mouse model of Rett syndrome — a severe neurodevelopmental condition caused by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2. 'Together, these findings highlight the therapeutic potential of microglial replacement in modifying the course of monogenic neurological diseases,' Du and Kipnis said. Looking ahead, they said it will be important to establish the optimal donor cell source to achieve 'scalable, safe, and durable microglial replacement.' 'It is also not yet clear whether the systemic toxicity caused by pretransplant conditioning can be minimized without compromising engraftment. Future strategies must strike a balance between replacement efficiency, systemic toxicity, and the functional competence of engrafted cells,' they wrote. 'Moving forward, it may ultimately become possible to reprogram the brain's immune landscape from within and find the best microglial replacement approach not only for microgliopathies but for a spectrum of neurological diseases,' Du and Kipnis concluded.
Yahoo
06-06-2025
- Business
- Yahoo
Otsuka tops Vera with kidney drug data; Regenxbio sinks on Duchenne update
This story was originally published on BioPharma Dive. To receive daily news and insights, subscribe to our free daily BioPharma Dive newsletter. Today, a brief rundown of news involving Otsuka Pharmaceutical and Arvinas, as well as updates from Regenxbio, Vigil Neuroscience and Sagimet Biosciences that you may have missed. Vera Therapeutics lost nearly a third of its market value Friday after Otsuka Pharmaceutical presented late-stage study data on a rival drug it's developing for the kidney disease IgA nephropathy. At a medical meeting, Otsuka said its therapy, sibeprenlimab, led to a 51% reduction in proteinuria, a key marker of kidney health, after nine months of treatment. Though cross-trial comparisons can be misleading, Vera's therapy led to a 42% reduction in proteinuria compared to placebo at a similar timepoint in its own Phase 3 study, causing investors to sell off company shares. Still, some analysts defended Vera. Jefferies' Farzin Haque cautioned not to 'overinterpret the data' and argued the two datasets 'are not clinically or statistically different for commercial uptake.' The Food and Drug Administration could approve Otsuka's drug by Nov. 28. On Monday, Vera said it intends to file an accelerated approval application in the fourth quarter. — Ben Fidler Arvinas and partner Pfizer have filed for a U.S. approval of their experimental protein-degrading drug for breast cancer, Arvinas said Friday. The two submitted the therapy, vepdegestrant, for use in people with estrogen-receptor positive, HER2 negative breast cancer and a mutation in the ESR1 gene. The application is based on Phase 3 data presented at the American Society of Clinical Oncology meeting this week showing the drug held tumors in check longer than a standard treatment. That benefit was modest, however, and wasn't observed in the overall study population. — Delilah Alvarado Regenxbio released new data Thursday showing a potential impact on muscle function among Duchenne muscular dystrophy patients who received its experimental gene therapy in an early-stage clinical trial. Regenxbio said those given the dose it's using in pivotal testing outperformed how historical data suggests they might on multiple widely used assessments of functional benefits. Still, shares fell by double digits, as some key information was missing from the update, the treatment's effects appear to be 'plateauing' and there is concern the data may not be strong enough to support an accelerated approval, wrote Jefferies analyst Maury Raycroft. Regenxbio expects to report pivotal data next year and has said it intends to seek a speedy approval afterwards, based on the therapy's ability to produce a tiny version of a muscle-protecting protein. — Ben Fidler Vigil Neuroscience reported Wednesday the failure of a mid-stage trial meant to prove its most advanced drug works as intended. The study enrolled 20 people with 'ALSP,' a rare disorder hallmarked by the erosion of white matter in the brain. All participants received Vigil's drug, VGL101, which is designed to boost the TREM2 proteins that help control inflammation in the brain. The company said that while showing favorable safety and tolerability, its treatment had no beneficial effects on important markers of effectiveness or biological activity. As such, a separate, so-called long-term extension study is being discontinued. Sanofi is in the process of acquiring Vigil for access to a different TREM2-targeting medicine. Per terms of that deal, rights to VGL101 will be returned to its original licensor, Amgen. — Jacob Bell Shares of Sagimet Biosciences have climbed nearly 40% since partner Ascletis Bioscience on Wednesday reported the company's drug denifanstat succeeded in a Phase 3 trial in China in people with moderate-to-severe acne. The drug produced 'compelling efficacy' in the trial with only mild-to-moderate side effects, which could have positive implications for its ability to treat metabolic dysfunction-associated steatohepatitis, Leerink Partners analyst Thomas Smith wrote in a research note. A 2019 partnership handed Ascletis rights in greater China to denifanstat. Sagimet could receive up to $122 million in future payments, as well as sales royalties, if the drug is approved. — Ben Fidler
Arabian Business
06-05-2025
- Business
- Arabian Business
Arcapita expands US private equity portfolio with the acquisition of Trustpoint
Arcapita Group Holdings Limited (' Arcapita '), the global alternative investment firm, announced today that it has successfully completed the acquisition of a majority stake in Trustpoint. One ('Trustpoint' or the 'Company'), a leading provider of tech-enabled legal services to law firms and corporate clients in the United States, is headquartered in Atlanta, Georgia. Valued at over $400 billion, the US legal services market is highly fragmented and experiencing growing demand for alternative legal service providers (ALSPs) due to rising litigation volumes and the need for technology-driven solutions. Historically, litigation has not been linked to GDP growth and is generally insulated from macroeconomic trends. ALSPs are an integral part of the modern litigation landscape due to their ability to generate meaningful cost and time savings, and allow law firms to focus on higher value-added activities such as building case strategy. The market is projected to grow at a stable rate, driven by increasing regulatory complexity and data volumes. Trustpoint offers a comprehensive suite of legal services, including eDiscovery, managed review, legal staffing, and cybersecurity solutions. The company serves a diverse set of clients, including top 100 law firms and a variety of Fortune 500 companies. Trustpoint benefits from a scalable business model, robust technology platform, and high client retention, positioning it for continued growth in a rapidly evolving legal services market. Hisham A. Al Raee, CEO of Arcapita, said: 'This acquisition underscores Arcapita 's commitment to investing in recession-resilient sectors with strong fundamentals. The investment in Trustpoint is part of our broader global essential business services strategy and builds on Arcapita's strong track record.' Neil Carter, Managing Director of US Private Equity at Arcapita, added: 'Trustpoint's position as a leading alternative legal services provider, combined with its strong client relationships and scalable platform, aligns well with our investment philosophy. The legal services industry is rapidly transforming, and Trustpoint is at the forefront of this shift with its technology-driven solutions. We are excited to support the company as it expands its market presence and continues to deliver best-in-class services to its clients. We look forward to working alongside Trustpoint's leadership team to drive the company's next phase of growth.' Mark Hawn, Founder and Chairman of Trustpoint, said: 'This partnership with Arcapita marks a significant milestone in Trustpoint's journey. Over the years, we have built a leading platform that delivers critical legal services through innovation and expertise. With Arcapita's global network and strategic insights, we are well-positioned to accelerate our growth, invest in cutting-edge technologies, and expand our service offerings to meet the evolving needs of our clients. We look forward to the opportunities this collaboration will unlock as we continue to lead the transformation of the legal services industry.' Chris Gallagher, CEO of Trustpoint, added: 'We are thrilled to partner with Arcapita as we embark on this next chapter of growth. Arcapita's deep expertise in scaling business services companies and its commitment to value creation make it the ideal partner for Trustpoint and our seasoned leadership team. With their support, we will continue to enhance our service offerings, invest in technology and employees, and expand our footprint across the legal services market.'
Yahoo
01-03-2025
- Business
- Yahoo
Why Vigil Neuroscience, Inc. (VIGL) is Skyrocketing So Far in 2025
We recently published an article titled . In this article, we are going to take a look at where Vigil Neuroscience, Inc. (NASDAQ:VIGL) stands against the other biotech stocks. No matter the market environment, you'll always find entertainment in the biotech space. There will always be biotech stocks making huge swings in both directions and these stocks can make or break your portfolio in a very small amount of time due to the nature of how important clinical trial results are for these companies. The United Nations forecasts that the over-65 age group will grow by 150% from 800 million in 2024 to 2 billion by 2067. This "older, richer & sicker" population is expected to push global healthcare spending on medicines up 12% to $2.3 trillion by 2028. If you combine that with AI making breakthroughs in healthcare more frequent, you'll see many more biotech stocks starting to pop to the upside over the coming years. For this article, I screened the top-performing biotech stocks year-to-date. I will also mention the number of hedge fund investors in these stocks. Why are we interested in the stocks that hedge funds pile into? The reason is simple: our research has shown that we can outperform the market by imitating the top stock picks of the best hedge funds. Our quarterly newsletter's strategy selects 14 small-cap and large-cap stocks every quarter and has returned 373.4% since May 2014, beating its benchmark by 218 percentage points (). A medical technician observing a petri dish containing a monoclonal antibody sample. Number of Hedge Fund Holders In Q4 2024: 18 Vigil Neuroscience, Inc. (NASDAQ:VIGL) is a biotech company that makes treatments for rare and common neurodegenerative diseases by restoring the vigilance of microglia, the sentinel immune cells of the brain. The stock is up significantly so far in 2025 in anticipation of upcoming clinical trial data readouts in the first half of 2025. It already reported positive Phase 1 clinical trial data for VG-3927 (small molecule TREM2 agonist) for Alzheimer's disease. Plus, a final analysis from the IGNITE Phase 2 clinical trial evaluating iluzanebart in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is planned for Q2 2025. In addition, it surged following announcements about promising progress in clinical trials for Alzheimer's and ALSP in January. The consensus price target of $19.75 implies 699.6% upside. Vigil Neuroscience, Inc. (NASDAQ:VIGL) is up 45% year-to-date. Overall VIGL ranks 15th on our list of the biotech stocks that are skyrocketing so far in 2025. While we acknowledge the potential of VIGL as an investment, our conviction lies in the belief that some AI stocks hold greater promise for delivering higher returns and doing so within a shorter time frame. If you are looking for an AI stock that is more promising than VIGL but that trades at less than 5 times its earnings, check out our report about the . READ NEXT: Why These 15 E-Commerce Stocks Are Skyrocketing So Far In 2025 and Disclosure: None. This article is originally published at Insider Monkey.
