Biomed Research Institute

BackgroundOver the past two decades, anti‐amyloid beta (Aβ) monoclonal antibodies have dominated Alzheimer’s disease (AD) drug development. While three agents—aducanumab, lecanemab, and donanemab—have received FDA approval, the broader clinical trial record for this drug class raises concerns about efficacy and safety. This study reviews and statistically analyzes trial outcomes across major anti‐Aβ antibodies to determine whether recent approvals mark true clinical progress—or signal the need for a paradigm shift in AD research.MethodWe systematically reviewed published Phase 2 and Phase 3 clinical trials of anti‐Aβ monoclonal antibodies, including aducanumab, bapineuzumab, crenezumab, donanemab, gantenerumab, lecanemab, ponezumab, semorinemab, and solanezumab. We focused on two outcome measures that were most frequently reported ‐ Clinical Dementia Rating Scale–Sum of Boxes (CDR‐SB) and Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog). The primary endpoints analyzed were the (CDR‐SB) and (ADAS‐Cog). We use bootstrapping methodology, a machine‐learning statistical procedure that resamples from a single dataset (with replacement) to create multiple samples. A bootstrapping method with 10,000 resamples was used to estimate mean differences and 95% confidence intervals (CI).ResultAll studies were randomized, placebo‐controlled trials with durations of 76 to 105 weeks (median: 78 weeks). Sample sizes ranged from 253 to 1,072 participants per arm. Pooled results showed:• CDR‐SB: mean difference = –0.08 (95% CI: –0.31 to +0.22). The score range for CDR‐SB is 0 to 18• ADAS‐Cog: mean difference = –0.53 (95% CI: –1.03 to +0.22). The score range for ADAS‐Cog is 0 to 70/90.• In both cases, the confidence intervals included zero, indicating no statistically or clinically significant benefit.ConclusionThe minimal differences between treatment and placebo—relative to the wide scoring scales—suggest that targeting amyloid plaques may be insufficient as a disease‐modifying approach. These findings underscore the urgent need for alternative strategies. One such approach is NA‐831, Biomed’s novel small‐molecule therapy based on neurogenesis and neuroprotection. Unlike amyloid‐targeted antibodies, NA‐831 aims to restore neuronal function and cognition by stimulating endogenous brain repair mechanisms. These emerging strategies may better align with the complex pathophysiology of AD and represent a promising new frontier in treatment.

Although chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction often coexist with overlapping clinical features, they are usually studied separately. The SPIROMICS HF (Subpopulations and Intermediate Outcome Measures in COPD and Heart Failure Study) is testing hypotheses that new computed tomography emphysema subtypes are associated with specific cardiovascular phenotypes (eg, cor pulmonale, cor pulmonale parvus), common airway branch variants are associated with right heart dysfunction, and symptomatic tobacco-exposed persons with preserved spirometry have signs of increased left ventricular afterload. SPIROMICS is a multicenter observational study of COPD with extensive pulmonary phenotyping of participants with ≥20 pack-years smoking and nonsmoking controls. COPD and COPD severity were defined by standard spirometric criteria and symptomatic tobacco-exposed persons with preserved spirometry by ≥20 pack-years, normal spirometry, and COPD Assessment Test score >10. SPIROMICS HF selected all participants in SPIROMICS visit 5 at major sites. Its comprehensive speckle-tracking echocardiography, which included physiological perturbations of leg raise and low-intensity exercise, was harmonized prospectively with the Multi-Ethnic Study of Atherosclerosis Early Heart Failure and HeartSHARE (Combining Omics, Deep Phenotyping, and Electronic Health Records for Heart Failure Subtypes and Treatment Targets) studies. The cardiopulmonary magnetic resonance imaging protocol with gadolinium administration included myocardial fibrosis sequences, pulmonary angiography, time-resolved 3-dimensional cine magnetic resonance imaging (4-dimensional flow) of venous return, and metronome-paced tachypnea to induce dynamic hyperinflation. Coronary artery calcium was assessed on computed tomography scans. The Kansas City Cardiomyopathy Questionnaire was administered. Of the final sample of 753 participants, 57% had COPD (15% mild, 27% moderate, and 15% severe), 18% had symptomatic tobacco-exposed persons with preserved spirometry, 16% were smoking controls, and 8% were nonsmoking controls. Reproducibility of the main measures from speckle-tracking echocardiography (intraclass correlation coefficient, 0.83-0.99), exercise echocardiography (intraclass correlation coefficient, 0.71-0.99) and magnetic resonance imaging (intraclass correlation coefficient, 0.57-0.99) were good-to-excellent, including in severe COPD. SPIROMICS HF aims to characterize and understand cardiopulmonary interactions in COPD and COPD-related phenotypes to inform targeted treatments for combined cardiopulmonary failure.

Epigenetic clocks are widely used to estimate biological aging, yet most are built from array-based data from peripheral tissues of predominantly European-ancestry individuals, limiting generalizability. Here, we present aging clocks trained using GenoML, an automated machine learning platform for clinical and multi-omics data, on DNA methylation from Oxford Nanopore long-read sequencing. These models leverage over 28 million CpG sites across individuals of African and European ancestry. Our findings highlight the power of long-read methylation data for constructing accurate, ancestry-aware aging clocks and emphasize the importance of inclusive training datasets.

Abstract BackgroundNA‐831 is a candidate for the treatment of Alzheimer’s Disease (AD). NA‐911 is an analog of NA‐831, serving as an IGF‐1 and GLP‐1 agonists. Animal studies of NA‐911 are evaluated for the treatment of by hypoxic‐ischemic injury, hemorrhagic stroke, and chronic neurodegenerative disordersMethodFor NA‐831: A randomized clinical trial of NA‐831 was performed in 112 participants with mild and moderate AD, half received the drugs and half received placebo. The patients with MCI received 10 mg of NA‐831 or placebo orally per day. The patients with mild and moderate AD received 30 mg of NA‐831 or placebo orally per day. Subjects with MCI to meet the NIA‐AA core clinical criteria, CDR score of 0.5 and a Memory Box score of 0.5 or greater at Screening and Baseline. MMSE score ≥22. Subjects with mild & moderate AD to meet the NIA‐AA core clinical criteria. MMSE: 17‐21.For NA‐911: We conducted animal studies of NA‐911 on adult male Sprague‐Dawley rats using the middle coronary artery occlusion (MCAO) method. This method is designed to mimic neurological and behavioral signs and symptoms of stroke in humans. Details of the animal study method will be described.ResultsNA‐831 showed a significant improvement for patients with mild and moderate AD with the ADAS‐Cog‐13 score change of an average of 4.1 as compared to the placebo after 24 weeks of treatment (p = 0.001; ITT). CIBIC‐Plus showed 78% patients improved (p = 0.01; ITT). mNA‐831 was well‐tolerated at 30 mg/day.In the animal study of NA‐911, the area of infarct in animals treated with vehicle was 43.4±7.4 mm2 (n = 13, Treatment with NA‐911 (3 mg/kg/h) significantly reduced the area of the infarct to 17.3 ±5.4 mm2 when compared to its vehicle treated group (n = 15, * P<0.05). It has been shown that progenitor cells residing in the SVZ are potentially able to replace the loss of nervous tissue after stroke.ConclusionAn association of Alzheimer’s disease and stroke has been suggested with clinical studies of NA‐831 and NA‐911. However, whether this association is causal requires further evaluation.

Objective: Hair loss is a common scalp concern for both men and women. Broccoli (Brassica oleracea var. Italica) is a vegetable plant in the cabbage family or brassicaceae that has antioxidant activity and levels of flavonoids that can encourage hair growth. Hair tonic is one of cosmetic products that contain ingredients to nourish hair. The purpose of this study was to investigate the physical stability and activity of hair development in hair tonic preparations using broccoli stalks extracted at different concentrations of 30%, 35%, and 40%, followed by an examination of the hair growth activity test in an animal model. Methods: This study hair tonic was prepared with Broccoli (Brassica oleracea var. Italica), the sample used the broccoli stalks, which was taken by purposive sampling. Evaluation of the preparation includes physical characteristic observation, pH examination, homogeneity of the preparation, irritation test, and stability test of the preparation using a cycling test, and check the activity test of hair growth in rats’ skin. Results: The results showed that the hair tonic preparation containing broccoli stalks extracts was stable at a temperature (4 °C±40 °C) where the odor, color, shape, homogeneity, and pH remained constant. In statistical testing using ANOVA analysis, each group of the hair tonic formula of broccoli stalks extract showed hair growth activity in male white rats. The hair tonic formulation containing 40% broccoli stalks extract had better hair growth activity compared to the 30% and 35% formula groups. The hair tonic prepared from broccoli extract is confirmed safe for use after successfully passing the skin irritation test. Conclusion: The hair tonic of broccoli extracts had met the standard of physical characteristics during storage time and it has a good activity test on hair growth in male white rats. This study provides a novel formulation in hair growth.

Introdução: Houve milhares de casos de contágio por Toxoplasma gondii em gestantes desde sua descoberta, sendo que, as consequências da doença variam de acordo com o trimestre da gravidez, tendo como complicações mais graves o aborto ou até mesmo a hidrocefalia. É importante o conhecimento detalhada de cada etapa das consequências causadas por toxoplasmose congênita, de acordo com os trimestres, pois, são as primeiras etapas que decidirão o futuro do feto. Objetivos: Descrever as possíveis consequências da toxoplasmose congênita, explicando sobre o que é o parasito Toxoplasma gondii e quais são as principais medidas profiláticas. Metodologia: Utilizou-se a forma bibliográfica tendo como classificação revisão de literatura. Critérios de inclusão foram artigos com data de publicação menores ou iguais que quatro anos, artigos relacionados à toxoplasmose no período gestacional e toxoplasmose congênita. Critérios de exclusão adotados foram artigos com publicações maiores ou iguais do que cinco anos, artigos com fuga ao tema, blogs, sites sem certificados de segurança. Conclusão: Na população é possível encontrar sorologia positiva para o Toxoplasma gondii. Em gestantes, observou-se que no primeiro trimestre, é possível o diagnóstico precoce, evitando assim a contaminação transplacentária. Consequências mais fatais para o feto se dá no primeiro trimestre, podendo chegar ao aborto. Já no último trimestre, as taxas de contaminação são baixas, podendo a criança nascer saudável. Fazem-se necessários a consulta de pré-natal e o acompanhamento nos períodos trimestrais, pois estes fatores poderão prevenir a possível contaminação tanto para a gestante, quanto para o feto.

Hibernation or torpor are energy-saving strategy in some thermostatic animals to survive harsh environments such as extreme cold and starvation. The ability to induce such hypometabolic states has garnered considerable interest due to its potential medical benefits. However, the mechanisms regulate these hypometabolic state remain largely unknown. Here we found that chemogenetic activation of astrocytes, a type of glial cell, could induce a torpor-like hypometabolic state in mice. In this state, body temperature and levels of oxygen consumption are kept low as in torpor. Glial activation induced hypothermia inhibited by intracerebroventricular administration of receptor X antagonist. Our findings could enable the induction of hypometabolism at any given time, and thus provide a new method for studying the mechanisms of hypometabolism. Furthermore, our results suggest the importance of glia-neural interaction in the study of hibernation and torpor.