RPEP-07216 · 2023Nusinersen (Spinraza), the first FDA-approved antisense therapy for spinal muscular atrophy, faces significant delivery challenges because it must be injected directly into the spinal canal. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) — antisense drugs linked to cell-penetrating peptides like Pip and DG9 — offer a potential solution by improving both intracellular uptake and systemic distribution.
The review traces how SMA is caused by mutations in the SMN1 gene, leaving patients dependent on the backup SMN2 gene that produces mostly non-functional protein (~90% defective). Antisense therapy corrects SMN2 splicing to produce functional SMN protein, but getting the drug into motor neurons throughout the body remains the central challenge that peptide conjugation aims to solve.
Nakevska, Zorica; Yokota, Toshifumi · Review
RPEP-07222 · 2023GLP-1 receptor agonists have shown promise in treating MASH (formerly NASH) in phase II trials and are now in phase III testing. Newer dual and triple agonists combining GLP-1 with glucagon and/or GIP activity have demonstrated improvements in weight, insulin resistance, and non-invasive liver markers. However, it remains unclear whether these drugs act directly on liver disease or primarily work through upstream weight loss and metabolic improvements. The authors suggest that combining gut hormone agonists with agents that directly target fibrosis (like FGF21 or pan-PPAR agonists) may be the most effective strategy.
Newsome, Philip N; Ambery, Phil ·
RPEP-07225 · 2023Cell-penetrating peptides can be conjugated with FDA-approved drugs to deliver them to the posterior segment of the eye via topical application, as demonstrated in animal models. This approach could reduce or eliminate the need for frequent intravitreal injections currently required for retinal diseases. The review catalogues various CPP types, their mechanisms of membrane translocation, and emerging peptide-based therapeutics for ocular conditions.
Nhàn, Nguyễn Thị Thanh; Maidana, Daniel E; Yamada, Kaori H ·
RPEP-07233 · 2023The ES2 peptide, which is CR3-based, showed 3–7 times greater senolytic effectiveness than the FOXO4-based DRI peptide. ES2 had higher affinity for the CR3-BDB interaction, which the study identified as crucial for the aging process. The computational analysis confirmed that CR3-based peptides are more potent senolytics overall, consistent with previous experimental findings.
Nwankwo, Norbert; Okafor, Ignatius ·
RPEP-07234 · 2023A state of partial natriuretic peptide deficiency — characterized by lower plasma NP concentrations — appears to be integral to conditions that precede overt cardiometabolic disease, particularly obesity and type 2 diabetes. Multiple factors affect NP levels: age, sex, race, genetics, and diurnal rhythms. The review highlights that O-glycosylation of NP precursor peptides is highly variable and affects both biomarker measurement accuracy and actual cardiovascular effects. An important proportion of people may have reduced effective NP bioactivity (receptor activation and physiological effects) even when measured peptide levels appear adequate.
Nyberg, Michael; Terzic, Dijana; Ludvigsen, Trine P; Mark, Peter D; Michaelsen, Natasha B; Abildstrøm, Steen Z; Engelmann, Mads; Richards, A Mark; Goetze, Jens P ·
RPEP-07235 · 2023Chemical glycosylation of somatostatin analogs with human complex-type N-glycans (oligosaccharides) achieved two goals simultaneously:
1. Metabolic stability — the glycosylated analogs resisted the rapid plasma degradation that limits native somatostatin's clinical use
2. Broad receptor affinity — the analogs maintained high binding affinity to all five somatostatin receptor subtypes (sst1-5)
This is notable because existing somatostatin drugs (like octreotide and lanreotide) sacrifice broad receptor coverage for stability — they are metabolically stable but only bind strongly to sst2 and sst5. The glycosylated analogs achieve both properties. The authors conclude that chemical glycosylation is a powerful general strategy for improving peptide and protein drug candidates.
Ochiai, Hirofumi; Shimoda, Taiji; Fukae, Kazuhiro; Maeda, Masatoshi; Ishii, Kazuyuki; Yoshida, Kenta; Tezuka, Katsunari; Tazuru, Keisuke; Saijo, Hayato; Asai, Hiroaki; Kanatani, Akio; Nishiuchi, Yuji ·
RPEP-07240 · 2023Co-culturing L. rhamnosus GG and S. thermophilus SY-102 in whey produced higher protein hydrolysis (453 μg/mL free amino groups), more low molecular weight peptides, and the highest ACE inhibition activity (53.42%) compared to either bacterium alone. The co-culture fermentation extended the logarithmic growth phase to 24 hours, enabling more extensive protein breakdown into bioactive peptides.
Olvera-Rosales, Laura Berenice; Pérez-Escalante, Emmanuel; Castañeda-Ovando, Araceli; Contreras-López, Elizabeth; Cruz-Guerrero, Alma Elizabeth; Regal-López, Patricia; Cardelle-Cobas, Alejandra; González-Olivares, Luis Guillermo ·
RPEP-07246 · 2023Among 20 migraine patients who failed CGRP ligand antibodies (galcanezumab or fremanezumab), switching to the CGRP receptor antibody erenumab produced meaningful results: 35% responded at 3 months and 45% responded at 6 months (≥30% reduction in monthly headache days). Monthly headache days decreased from a baseline of 18.6 by 4.1 days at 3 months and 7.0 days at 6 months (both p<0.001). The improving response over time suggests that some patients may need longer than 3 months to benefit from the switch. No demographic or headache characteristics predicted who would respond.
Overeem, Lucas Hendrik; Lange, Kristin Sophie; Fitzek, Mira Pauline; Siebert, Anke; Steinicke, Maureen; Triller, Paul; Hong, Ja Bin; Reuter, Uwe; Raffaelli, Bianca · Retrospective Cohort
RPEP-07248 · 2023Among 76 atopic children aged 0-5, sensitization rates to plant storage proteins were: 25% to 2S albumins, 19.7% to 7S globulins, 13.2% to 11S globulins, and 1.3% to cereal prolamins. The most common allergens were peanut proteins: Ara h 1 (18.4%), Ara h 2 (17.1%), Ara h 6 (15.8%), and Ara h 3 (11.8%), with mean sIgE concentrations of 10.93, 15.353, 15.359, and 9.038 kUA/L respectively.
MALDI-TOF mass spectrometry revealed that four proteins were altered in children allergic to storage proteins: cell cycle control protein 50A, testis-expressed sequence 13B, DENN domain-containing protein 5A, and SKI family transcriptional corepressor 2.
Packi, Kacper; Matysiak, Joanna; Matuszewska, Eliza; Bręborowicz, Anna; Matysiak, Jan ·
RPEP-07250 · 2023Mesoporous silica nanoparticles (MSNs) offer multiple advantages for oral peptide delivery: their pore size and surface can be precisely tailored to load and protect peptides, they have high surface area for drug loading, excellent thermal stability, and good biocompatibility. MSNs can be engineered to respond to specific stimuli (such as pH changes in the gut) to control when and where peptides are released, potentially overcoming the major barriers of enzymatic degradation, poor membrane permeability, and low bioavailability that currently limit oral peptide therapeutics.
Pamshong, Sharon Rose; Bhatane, Dhananjay; Sarnaik, Santosh; Alexander, Amit ·
RPEP-07252 · 2023Human beta defensin-1 (hBD-1) was shown to target the tumor-specific biomarker thioredoxin (Trx) and activate two cell death pathways — CD95 (Fas) and ASK1 (apoptosis stimulating kinase 1) — that are dysregulated in TNBC. Injection of hBD-1 into TNBC mouse models restored the peptide to basal levels and sensitized previously resistant cancer cells to doxorubicin chemotherapy.
The combination of hBD-1 restoration plus doxorubicin produced significant tumor volume reduction in vivo compared to chemotherapy alone. This represents the first demonstration that injecting hBD-1 can restore its tumor-suppressor function and sensitize TNBC to chemotherapy in a living animal model.
Pandurangi, Raghu S; Sekar, Thillai V; Paulmurugan, Ramasamy ·
RPEP-07256 · 2023This review traces the evolution of somatostatin analogue-based radiopharmaceuticals from the first in vivo tumor imaging in 1989 to modern peptide receptor radionuclide therapy (PRRT). Key milestones include: 111In-OctreoScan for SPECT imaging, the shift to PET tracers like 68Ga-DOTATOC and 68Ga-DOTATATE with improved sensitivity, and therapeutic applications using 90Y-DOTATOC and 177Lu-DOTATATE for treating inoperable or metastatic neuroendocrine tumors.
The newest frontier is targeted alpha-particle therapy (TAT) using actinium-225 (225Ac)-DOTATATE and bismuth-213 (213Bi)-DOTATOC, which showed partial tumor responses without significant toxicity. PRRT side effects are few and mild when kidney protection measures and dose limits are followed. For all approaches, the somatostatin analogue peptide serves as the targeting vehicle that delivers the radioactive payload specifically to tumor cells expressing somatostatin receptors.
Papachristou, Maria · Review
RPEP-07257 · 2023The review catalogues all known DNA-binding stapled peptides in the literature, noting that despite the strong parallel to protein-protein interaction (PPI) disrupting stapled peptides, very few DNA-binding examples exist. Key observations include:
Stapled peptides have proven highly successful at mimicking α-helical protein surfaces to disrupt PPIs, with at least one example in clinical trials. Since DNA-protein interactions are also frequently mediated by α-helices — particularly in transcription factors — the same stapling approach should theoretically apply to DNA binding. Unlike DNA-binding small molecules, which typically lack sequence selectivity, stapled peptides modeled on transcription factor helices could achieve both high affinity and high DNA sequence selectivity.
Paquette, André R; Boddy, Christopher N ·
RPEP-07260 · 202368Ga-DOTATATE PET/CT effectively diagnoses lung carcinoids with high somatostatin receptor (SSTR) expression. Combining this with 18F-FDG PET/CT reveals tumor heterogeneity, which is critical for identifying which patients are most likely to benefit from PRRT.
PRRT may serve as an effective and safe treatment for advanced lung carcinoids that progress during first-line somatostatin analog therapy. The theragnostic approach — using the same peptide target for both imaging and treatment — represents a paradigm shift in neuroendocrine tumor management.
Park, Hyesun; Subramaniam, Rathan M ·
RPEP-07261 · 2023This meta-analysis of 24 randomized controlled trials (3,377 patients) found that GLP-1 analogs — particularly liraglutide — provide meaningful benefits when added to insulin therapy in type 1 diabetes. Liraglutide produced dose-dependent reductions in A1c (-0.09% per mg), body weight (-2.2 kg per mg), and total daily insulin (-4.32 IU per mg).
However, higher liraglutide doses came with significantly increased nausea (OR 6.5) and modestly elevated ketosis risk (OR 1.8). Importantly, GLP-1 therapy did not significantly increase severe or symptomatic hypoglycemia. Patients who were newly diagnosed or still producing some insulin (C-peptide positive) showed greater A1c reductions (-0.51% vs -0.28%) but similar weight loss.
Park, Jeayoung; Ntelis, Spyridon; Yunasan, Elvina; Downton, Katherine D; Yip, Terry Cheuk-Fung; Munir, Kashif M; Haq, Nowreen · Systematic Review Meta Analysis
RPEP-07262 · 2023Older adults (≥50 years) who took 15 grams of low-molecular collagen peptides daily for 12 weeks experienced a significant reduction in body fat mass compared to placebo, confirmed by two independent measurement methods (BIA and DEXA).
The collagen group saw a -0.49% change in total fat mass while the placebo group gained 2.23% (p=0.041). Within the collagen group, significant reductions were observed in whole body fat mass (p=0.002), whole body fat percentage (p=0.002), trunk fat mass (p=0.001), and trunk fat percentage (p<0.001). Importantly, physical activity levels, dietary intake, and blood biochemistry did not differ between groups, suggesting the effect was from the collagen supplementation itself.
Park, Jeongbin; Kim, Minji; Shin, Hyeri; Ahn, Hyejin; Park, Yoo Kyoung · Randomized Controlled Trial
RPEP-07270 · 2023An expert consensus survey established standardized nomenclature for the ghrelin system: 'ghrelin' (the octanoylated active peptide), 'desacyl-ghrelin' (the non-acylated form that does not bind GHSR at physiological levels), 'GHSR' (growth hormone secretagogue receptor), and 'LEAP2' (liver-expressed antimicrobial peptide 2, a recently recognized endogenous GHSR antagonist/inverse agonist).
The paper also contextualizes that ghrelin controls not only growth hormone secretion but also food intake, reward-related behaviors, glucose homeostasis, and gastrointestinal motility. Desacyl-ghrelin's physiological role remains less well-characterized despite being detectable in biological samples.
Perelló, Mario; Dickson, Suzanne L; Zigman, Jeffrey M; Leggio, Lorenzo ·
RPEP-07272 · 202334 novel synthetic analogs of DNA bis-intercalating peptides were synthesized and characterized. Initial ADC constructs were hydrophobic and aggregation-prone. Two strategies improved properties: solubilizing linker groups and enzymatically cleavable hydrophilic masks. All ADCs showed potent in vitro cytotoxicity in high-antigen-expressing cells. Masked ADCs were less potent in low-antigen cell lines. In vivo, stochastically conjugated DAR4 anti-FRα ADCs were toxic at low doses, while site-specific THIOMAB DAR2 anti-cMet ADCs were well-tolerated and highly efficacious — demonstrating that conjugation strategy critically affects the therapeutic window.
Petersen, Mark E; Brant, Michael G; Lasalle, Manuel; Fung, Vincent K C; Rojas, Andrea Hernandez; Wong, Jodi; Das, Samir; Barnscher, Stuart D; Rich, Jamie R; Winters, Geoffrey C ·
RPEP-07276 · 2023Under normal growth conditions, intracellular free calcium and Thymosin β4 concentrations are strictly regulated and unaffected by extracellular supplementation. However, cell starvation decreases intracellular Thymosin β4 levels and increases uptake of extracellular peptide above the normal range. Most significantly, cell starvation dramatically increases internalization of extracellular Ca2+/Thymosin β4 complexes, suggesting a starvation-triggered mechanism that could be relevant to the early stages of cancer metastasis.
Piludu, Marco; Pichiri, Giuseppina; Coni, Pierpaolo; Piras, Monica; Congiu, Terenzio; Faa, Gavino; Lachowicz, Joanna Izabela ·
RPEP-07279 · 2023The review identifies several major developments in GPCR-targeted obesity therapeutics:
1. Semaglutide established the benchmark as the first peptide GLP-1 receptor agonist achieving ≥10% weight loss with cardiovascular benefits (MACE reduction)
2. Dual GLP-1/GIP agonists (like tirzepatide) demonstrate enhanced weight loss over single-target GLP-1 drugs
3. Triple agonists targeting GLP-1, GIP, and glucagon receptors simultaneously are in development for even greater efficacy
4. Oral formulations are advancing, including oral semaglutide tablets and small molecule non-peptide GLP-1 receptor agonists
5. Fixed-dose combinations and add-on therapies are being developed for patients who need weight loss beyond what single-agent GLP-1 therapy provides
Pocai, Alessandro ·
RPEP-07284 · 2023In Part A (single dose, n=32), orforglipron showed dose-proportional pharmacokinetics with a half-life of 24.6–35.3 hours across doses of 0.3–6 mg. In Part B (multiple dose, n=60), 4 weeks of daily dosing with escalation to final target doses of 2–24 mg resulted in extended half-lives of 48.1–67.5 hours.
Participants receiving orforglipron lost up to 5.4 kg of body weight after 4 weeks compared to 2.4 kg with placebo (P < 0.05). Fasting glucose levels decreased across the treatment period, and gastric emptying was delayed on Day 28 — all consistent with GLP-1 receptor activation. The most common adverse events were gastrointestinal, similar to injectable GLP-1 receptor agonists.
Pratt, Edward; Ma, Xiaosu; Liu, Rong; Robins, Deborah; Haupt, Axel; Coskun, Tamer; Sloop, Kyle W; Benson, Charles ·
RPEP-07285 · 2023Across multiple dosing regimens over 12 weeks, orforglipron produced mean HbA1c reductions of 1.5% to 1.8%, compared to 0.4% with placebo. Body weight changes ranged from -0.24 kg to -5.8 kg with orforglipron, versus +0.5 kg with placebo.
The drug had a half-life of 29-49 hours at Week 12, supporting once-daily dosing. Weekly dose escalation was shown to be generally well tolerated, providing guidance for future dosing protocols.
The most common adverse events were gastrointestinal-related and occurred early in treatment, consistent with the known class effects of GLP-1 receptor agonists. No new safety signals were identified beyond what is expected for this drug class.
Pratt, Edward; Ma, Xiaosu; Liu, Rong; Robins, Deborah; Coskun, Tamer; Sloop, Kyle W; Haupt, Axel; Benson, Charles ·
RPEP-07294 · 2023The researchers identified a previously unknown population of AgRP-negative NPY neurons in the arcuate nucleus of the hypothalamus. Under positive energy balance (high-fat diet or genetic obesity), NPY2 receptor expression increases specifically on POMC neurons — the cells that normally signal fullness.
This upregulation allows NPY released from the newly discovered AgRP-negative neurons to override POMC satiety signaling and alter leptin responsiveness. When the researchers artificially activated this circuit using chemogenetics, mice ate significantly more. When they inhibited it with optogenetics, feeding decreased. Mice lacking NPY2 receptors on their POMC neurons ate less and had lower body fat.
Qi, Yue; Lee, Nicola J; Ip, Chi Kin; Enriquez, Ronaldo; Tasan, Ramon; Zhang, Lei; Herzog, Herbert · Animal
RPEP-07303 · 2023Across 13 open-label trials (ranging 12-264 weeks) of all five CGRP-targeting drugs for migraine prevention, no new safety concerns emerged beyond those seen in double-blind phases. More than 75% of patients remained on treatment after one year, with sustained reductions in migraine frequency and lasting quality of life improvements. Discontinuation rates were generally low, and the adverse event profile was consistent with the controlled trial data.
Raffaelli, Bianca; De Icco, Roberto; Corrado, Michele; Terhart, Maria; Ailani, Jessica ·
RPEP-07311 · 2023Insulin-GET nanocomplexes (140 nm, +27.10 mV charge) enhanced insulin transport across differentiated Caco-2 intestinal epithelium by more than 22-fold compared to free insulin. The nanocomplexes accumulated inside cells and were progressively released from both the apical and basal surfaces, effectively turning gut cells into sustained-release depots.
The complexes showed enhanced proteolytic stability (resisting enzymatic destruction) and retained significant biological activity. In streptozotocin-induced diabetic mice, serial oral dosing of Insulin-GET nanocomplexes controlled elevated blood glucose levels over several days without compromising intestinal barrier integrity or cell viability.
Rehmani, Sahrish; McLaughlin, Christopher M; Eltaher, Hoda M; Moffett, R Charlotte; Flatt, Peter R; Dixon, James E · Preclinical Drug Delivery
RPEP-07313 · 2023Neurotrophic factors (NTFs) — including NGF, IGF-1, BDNF, VEGF, and TNF-α — are deeply involved in the pathophysiology of dementia, stroke, and traumatic brain injury, and represent high-value therapeutic targets. The neuropeptide preparation Cerebrolysin has been shown to mimic the activities of these NTFs and modulate the expression levels of endogenous neurotrophic factors.
Cerebrolysin demonstrated beneficial effects in both in vitro studies and clinical trials across all three conditions, acting through neuroplasticity, neurogenesis, angiogenesis, and anti-inflammatory pathways. The review emphasizes that these NTFs don't work in isolation — their signaling networks interact, and Cerebrolysin appears to engage multiple pathways simultaneously.
Rejdak, Konrad; Sienkiewicz-Jarosz, Halina; Bienkowski, Przemyslaw; Alvarez, Anton · Review
RPEP-07314 · 2023A growth hormone-releasing hormone agonist (MR409) reversed vascular calcification in diabetic mice over 8 weeks of daily treatment. The peptide eliminated calcium plaques from heart valves (confirmed by echocardiography), improved blood vessel function, and reduced vascular structural damage — all without significantly affecting growth hormone levels.
The mechanism involved upregulation of the anti-calcifying protein Klotho, reduction of vascular reactive oxygen species (ROS), and suppression of bone-forming genes (Runx2, ALP) that drive calcium deposition in blood vessels. The peptide also improved the lipid profile of diabetic mice.
Ren, Hao-Lin; Cai, Ruiping; Xue, Ruize; Zhang, Yaoxia; Xu, Qian; Zhang, Xianyang; Cai, RenZhi; Sha, Wei; Schally, Andrew V; Zhou, Ming-Sheng · Animal Study
RPEP-07315 · 2023Heating goat milk at temperatures ≥80°C caused more extensive gastric clot formation with higher protein digestion rates, but also resulted in more undigested whey proteins due to severe aggregation.
β-Casein was the major source of bioactive peptides during digestion. Milk heated at 65°C produced the highest abundance of bioactive peptides, while temperatures above 75°C reduced bioactive peptide levels because the peptides were further cleaved into smaller, less bioactive fragments. The study demonstrated that different heating temperatures induce different degrees of whey protein denaturation, which directly affects digestion outcomes.
Ren, Qing; Boiani, Mattia; He, Tao; Wichers, Harry J; Hettinga, Kasper A ·
RPEP-07320 · 2023All 6 patients (100%) with positive Alcohol Use Disorder Identification Test (AUDIT) screenings showed significant reduction in AUD symptoms after starting semaglutide therapy for weight loss. The mean AUDIT score decreased by 9.5 points, a statistically significant improvement (P value reported as significant via paired t-test).
This clinical observation is consistent with preclinical animal data showing that GLP-1 receptor agonists can reduce alcohol consumption. Currently, only 3 FDA-approved medications exist for AUD treatment, making the potential of semaglutide as an additional option clinically meaningful.
Richards, Jesse R; Dorand, Madisen Fae; Royal, Kyleigh; Mnajjed, Lana; Paszkowiak, Maria; Simmons, W Kyle ·
RPEP-07323 · 2023At 24 weeks, retatrutide produced dose-dependent HbA1c reductions:
• 0.5 mg: −0.43%
• 4 mg (escalation): −1.39%
• 4 mg (no escalation): −1.30%
• 8 mg (slow escalation): −1.99%
• 8 mg (fast escalation): −1.88%
• 12 mg (escalation): −2.02%
• Placebo: −0.01%
• Dulaglutide 1.5 mg: −1.41%
At 36 weeks, body weight decreased dose-dependently:
• 0.5 mg: −3.19%
• 4 mg (escalation): −7.92%
• 4 mg (no escalation): −10.37%
• 8 mg (slow): −16.81%
• 8 mg (fast): −16.34%
• 12 mg: −16.94%
• Placebo: −3.00%
• Dulaglutide: −2.02%
The 8 mg and 12 mg doses significantly outperformed both placebo (p<0.0001) and dulaglutide (p<0.0001 for weight; p≤0.0019 for HbA1c).
Rosenstock, Julio; Frias, Juan; Jastreboff, Ania M; Du, Yu; Lou, Jitong; Gurbuz, Sirel; Thomas, Melissa K; Hartman, Mark L; Haupt, Axel; Milicevic, Zvonko; Coskun, Tamer ·
RPEP-07325 · 2023Tachykinin precursor 1 (Tac1) neurons in the preBötzinger Complex (preBötC) — the brain's breathing rhythm generator — promote rhythmic breathing when stimulated. Using optogenetics, researchers showed that activating these substance P-expressing neurons stimulated breathing in both anesthetized and freely moving mice, triggered locomotion, and critically, overcame opioid-induced respiratory depression. These findings establish Tac1 neurons as a key excitatory population with dual roles in breathing and motor behavior.
Rousseau, Jean-Philippe; Furdui, Andreea; Silveira Scarpellini, Carolina da; Horner, Richard L; Montandon, Gaspard ·
RPEP-07327 · 2023HbA1c decreased significantly at both time points: -1.3% at 6 months (p<0.001) and -2.0% at 12 months (p<0.001). Body weight decreased by -2.0 kg at 6 months (p=0.002) and -3.5 kg at 12 months (p=0.001). A reduction in insulin dose was also observed in patients taking concurrent insulin.
The improvements were progressive — results at 12 months were better than at 6 months for both HbA1c and weight, suggesting continued benefit with ongoing treatment.
Ruda, Alexandru Ioan; Ciobanu, Dana Mihaela; Inceu, Georgeta; Rusu, Adriana; Roman, Gabriela ·
RPEP-07331 · 2023Fifty vestibular migraine patients treated with anti-CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) over 18 months:
- **Vertigo**: 45/50 patients (90%) achieved ≥50% reduction in vertigo frequency
- **Headache**: 43/50 patients (86%) achieved ≥50% reduction in headache frequency
- **Disability**: 40/50 patients (80%) had ≥50% reduction in MIDAS disability score
- **All three metrics**: 39/50 patients (78%) improved on vertigo, headache, AND disability simultaneously
- **Dizziness days**: Dropped from 10.3 ± 1.9 days/month at baseline to 0.8 ± 0.3 days/month at 12 months (difference 9.5 days, 95% CI 3.6-15.4, p<0.001)
Russo, Cinzia Valeria; Saccà, Francesco; Braca, Simone; Sansone, Mattia; Miele, Angelo; Stornaiuolo, Antonio; De Simone, Roberto ·
RPEP-07332 · 2023In a double-blind, placebo-controlled Phase III trial of 3,000 volunteers aged 18 and older, the two-dose EpiVacCorona vaccine administered intramuscularly demonstrated a prophylactic efficacy of 82.5% (95% CI: 75.3–87.6%) against COVID-19.
The safety profile was favorable: mild local reactions occurred in no more than 27% of vaccinated individuals, and mild systemic reactions in no more than 14%. The researchers concluded the vaccine was safe enough and effective enough for regular seasonal COVID-19 prevention.
Ryzhikov, Alexander B; Ryzhikov, Evgeny A; Bogryantseva, Marina P; Usova, Svetlana V; Nechaeva, Elena A; Danilenko, Elena D; Pyankov, Stepan A; Gudymo, Andrey S; Moiseeva, Anastasiya A; Onkhonova, Galina S; Pyankov, Oleg V; Sleptsova, Ekaterina S; Lomakin, Nikita V; Vasilyeva, Veronika S; Tulikov, Mikhail V; Gusarov, Vitaly G; Pulin, Andrey A; Balalaeva, Maria A; Erofeeva, Svetlana B; Terpigorev, Stanislav A; Rychkova, Olga A; Petrov, Ivan M; Delian, Viktoriia Y; Rafalskiy, Vladimir V; Tyranovets, Sergey V; Gavrilova, Elena V; Maksyutov, Rinat A · Human Rct
RPEP-07334 · 2023Three antimicrobial peptides — Melittin, Cecropin A, and a Cecropin A-Melittin hybrid — were tested against 3D colorectal cancer spheroids. All three peptides reduced cell viability and compromised spheroid structure. Melittin and the hybrid peptide were the most effective, showing greater anticancer activity than Cecropin A alone. The peptides increased ATP and LDH release (indicators of membrane damage and cell death), arrested cancer cells in the G2/M phase of the cell cycle, and increased the number of senescent (non-dividing) cells.
Răileanu, Mina; Bacalum, Mihaela ·
RPEP-07340 · 2023PEG-loxenatide (PEX168), a long-acting pegylated GLP-1 receptor agonist derived from exenatide, significantly improved blood sugar control when added to metformin. The meta-analysis of 6 RCTs with 1,248 patients found that PEX168 plus metformin significantly reduced fasting blood glucose (MD = -1.20 mmol/L) and HbA1c compared to metformin alone.
Weight loss was striking in obese patients — a 5.46 kg reduction versus controls — but no weight change occurred in non-obese patients. PEX168 monotherapy at 100, 200, and 300 μg showed comparable diabetes control to metformin. The 100 μg dose combined with metformin offered the best balance of efficacy and safety, while the 200 μg combination had more nausea and vomiting.
Salamah, Hazem Mohamed; Marey, Ahmed; Elsayed, Esraa; Hasan, Mohammed Tarek; Mahmoud, Abdelrahman; Abualkhair, Khaled Alsayed; Abo-Elnour, Dina Essam; Abdelhaleem, Ibrahim Abdelmonaem; Abd-Elgawad, Mohamed · Meta Analysis
RPEP-07346 · 2023Using multimer staining and a functional screening platform with single HLA-engineered antigen presenting cells, researchers detected 20 CD8+ T cell responses to 11 different endogenously processed HLA-peptide combinations across 12 HPV16-induced tumors. Specific HLA-peptide combinations dominated responses in patients expressing those HLA alleles.
T cell receptors (TCRs) reactive to seven different HLA class I-restricted peptides were isolated. Five of six analyzed TCRs showed tumor reactivity, confirming they recognize naturally processed and presented peptides on actual tumor cells. These TCRs could potentially be used for adoptive cell transfer immunotherapy.
Santegoets, Saskia J; Welters, Marij J P; Schrikkema, Deborah S; Freriks, Manon R; Kok, Hanna; Weissbrich, Bianca; van den Branden, Anouk; Linnemann, Carsten; Schumacher, Ton N; Adhikary, Sabina; Bendle, Gavin; van der Burg, Sjoerd H ·
RPEP-07357 · 2023In this double-blind, placebo-controlled trial, the MUC1 peptide vaccine successfully generated immune responses in 25% of recipients (13/52) — significantly more than placebo (0/50, p < 0.0001). However, the overall adenoma recurrence rate was not significantly different between vaccine (56.3%) and placebo (66.0%) groups (adjusted RR 0.83, p = 0.25). The most intriguing finding was among the subset who mounted a robust immune response at both 12 and 55 weeks: only 27.3% (3/11) developed recurrent adenomas versus 66% in the placebo group — a 38% absolute reduction (adjusted RR 0.41, p = 0.08). The vaccine showed no difference in serious adverse events compared to placebo.
Schoen, Robert E; Boardman, Lisa A; Cruz-Correa, Marcia; Bansal, Ajay; Kastenberg, David; Hur, Chin; Dzubinski, Lynda; Kaufman, Sharon F; Rodriguez, Luz M; Richmond, Ellen; Umar, Asad; Szabo, Eva; Salazar, Andres; McKolanis, John; Beatty, Pamela; Pai, Reetesh K; Singhi, Aatur D; Jacqueline, Camille M; Bao, Riyue; Diergaarde, Brenda; McMurray, Ryan P; Strand, Carrie; Foster, Nathan R; Zahrieh, David M; Limburg, Paul J; Finn, Olivera J · Randomized Controlled Trial
RPEP-07358 · 2023Diagnostic 68Ga-DOTATATE PET/CT has demonstrated improved sensitivity in detecting both primary and metastatic neuroendocrine lesions compared to conventional imaging and prior-generation somatostatin receptor imaging methods.
For treatment, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE has been validated by prospective randomized controlled studies showing beneficial impact on survival and quality of life. PRRT is now frequently included in the management of neuroendocrine neoplasms. However, the therapy is still considered palliative rather than curative and may be accompanied by adverse effects.
Schwarz, Jason L; Williams, Jelani K; Keutgen, Xavier M; Liao, Chih-Yi ·
RPEP-07360 · 2023Self-assembled peptide hydrogels represent a versatile class of biomaterials with applications spanning drug delivery, tissue engineering, cancer therapy, stem cell therapy, bioimaging, and regenerative medicine. Their biocompatibility, biodegradability, and ability to mimic natural tissue microenvironments make them particularly promising for targeted and stimulus-responsive drug release systems.
The review highlights that peptide hydrogels can be designed to respond to both internal stimuli (pH, enzymes, redox conditions) and external stimuli (temperature, light, ultrasound) for controlled therapeutic release. Key structural forms include micelles, hydrogels, and vesicles, each offering distinct advantages for specific biomedical applications.
Sedighi, Mahsa; Shrestha, Neha; Mahmoudi, Zahra; Khademi, Zahra; Ghasempour, Alireza; Dehghan, Hamideh; Talebi, Seyedeh Fahimeh; Toolabi, Maryam; Préat, Véronique; Chen, Bozhi; Guo, Xindong; Shahbazi, Mohammad-Ali · Review
RPEP-07362 · 2023This review covers oral semaglutide (Rybelsus), the first GLP-1 receptor agonist available as a pill rather than an injection. The drug combines semaglutide with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate), an absorption enhancer that helps the peptide cross the stomach lining intact.
Beyond blood sugar control, the review highlights that GLP-1 receptor agonists deliver significant weight loss with low hypoglycemia risk, reduce major adverse cardiovascular events, and may protect the kidneys in patients with type 2 diabetes and chronic kidney disease. Clinical trials have shown GLP-1 RA treatment is safe and tolerated in patients with impaired renal function.
Selvarajan, Raja; Subramanian, Rashmi · Review
RPEP-07370 · 2023Sardina pilchardus protein hydrolysate (SPH) produced using dispase and alkaline protease yielded peptide fractions with ACE inhibitory activity, with the low molecular mass fractions showing the strongest effects. The peptides also exhibited antioxidant properties.
Using LC-MS/MS combined with online database searching and molecular docking, the researchers identified novel peptide sequences with strong predicted binding to the ACE enzyme. The dual functionality — both ACE inhibition and antioxidant activity — makes these peptides particularly interesting for functional food development targeting cardiovascular health.
Shao, Mingyang; Wu, Haixing; Wang, Bohui; Zhang, Xuan; Gao, Xia; Jiang, Mengqi; Su, Ruiheng; Shen, Xuanri ·
RPEP-07374 · 2023Two-step enzymatic hydrolysis of corn distillers solubles (CDS) protein using alcalase followed by flavourzyme (AF) produced peptides with 97.68% ACE inhibition and 51.51% DPP4 inhibition — the highest dual bioactivity among all hydrolysis combinations tested. Nine novel peptides were identified by mass spectrometry from the most active fraction (<3 kDa), including APLA, PLFP, LFLP, LPPYL, PLYPLP, NDWHTGPL, LPPYLPS, GSPFLGQ, and SWQQPIVGG. Bioinformatic analysis confirmed these peptides can bind to the active sites of both ACE and DPP4 enzymes.
Sharma, Sonu; Pradhan, Ranjan; Manickavasagan, Annamalai; Tsopmo, Apollinaire; Thimmanagari, Mahendra; Dutta, Animesh ·
RPEP-07379 · 2023CTX-induced hypogonadism decreased LH, total and free testosterone, androgen receptor, androgen binding protein, and GSH-Px while increasing oxidative stress markers and impairing sexual behavior. Aerobic exercise combined with oyster peptide supplementation significantly reversed all these changes except serum LH. The combination was superior to exercise alone for serum total testosterone, FSH, testicular testosterone, mating latency, capture times, and mating times. Steroidogenic gene expression (StAR, P450scc, StARD7) was rescued by the combination treatment.
Shi, Wenting; Liu, Yu; Jin, Qiguan; Wu, Meitong; Sun, Qizheng; Li, Zheng; Liu, Wenying ·
RPEP-07382 · 2023Sacubitril/valsartan treatment significantly increased atrial natriuretic peptide (ANP) levels in patients with compensated heart failure — from a median of 102 pg/mL at baseline to 283 pg/mL at 3 months and 409 pg/mL at 6 months. Simultaneously, the daily furosemide (loop diuretic) dose was cut in half, from 40 mg to 20 mg. No such changes occurred in the ACE inhibitor comparison group.
Patients with preserved ejection fraction (HFpEF) and persistent atrial fibrillation showed the largest ANP increases, with odds ratios of 7.558 and 4.649 respectively for high ANP elevation.
Shirakabe, Akihiro; Matsushita, Masato; Sawatani, Tomofumi; Noma, Satsuki; Takayasu, Tsutomu; Kanai, Hideki; Asano, Miwako; Nomura, Akiko; Asai, Kuniya ·
RPEP-07386 · 2023Researchers built a physiologically based pharmacokinetic (PBPK) model that accurately predicts how two gallium-68-labeled somatostatin peptides — DOTATATE and HA-DOTATATE — distribute through the body and into tumors of neuroendocrine cancer patients. Key findings: the uptake differences between the two peptides in organs were driven by their different receptor binding affinities, while tumor uptake was primarily determined by tumor blood flow and blood volume. The 'tumor sink effect' — where large tumors absorb so much peptide that normal organs get less — was only clinically relevant when total tumor volume exceeded about 550 mL, which affects a minority of patients.
Siebinga, Hinke; de Wit-van der Veen, Berlinda J; Beijnen, Jos H; Dorlo, Thomas P C; Huitema, Alwin D R; Hendrikx, Jeroen J M A · Modeling Study
RPEP-07388 · 2023The review presents BPC 157 as a peptide with interconnected effects across the brain-gut and gut-brain axes in animal models. Reported findings include:
- Behavioral effects: anxiolytic, anticonvulsive, antidepressant activity, and counteraction of catalepsy and schizophrenia-like symptoms in animal models
- Muscle effects: healing and function recovery across various muscle injuries, both peripheral and central
- Cardiovascular effects: counteracted heart failure, arrhythmias, and thrombosis in animal models
- Organ protection: counteracted encephalopathies, liver and stomach lesions from NSAIDs and insulin, and multiorgan failure from major vessel occlusion
- Vascular effects: attenuated severe intracranial, portal, and caval hypertensions, and aortal hypotension
The authors frame these diverse effects as part of a unified network operating through the brain-gut axis.
Sikiric, Predrag; Gojkovic, Slaven; Krezic, Ivan; Smoday, Ivan Maria; Kalogjera, Luka; Zizek, Helena; Oroz, Katarina; Vranes, Hrvoje; Vukovic, Vlasta; Labidi, May; Strbe, Sanja; Baketic Oreskovic, Lidija; Sever, Marko; Tepes, Marijan; Knezevic, Mario; Barisic, Ivan; Blagaic, Vladimir; Vlainic, Josipa; Dobric, Ivan; Staresinic, Mario; Skrtic, Anita; Jurjevic, Ivana; Boban Blagaic, Alenka; Seiwerth, Sven ·
RPEP-07390 · 2023After initial PRRT, all 20 patients eventually progressed, with a median progression-free survival (PFS) of 32 months. Upon retreatment (PRRTR), median PFS was 17.5 months (IQR: 7–39 months). At analysis, 15 of 18 evaluable patients had progressed after retreatment, while 3 had stable disease.
The median overall survival from the first cycle of initial treatment was 66 months (IQR: 65–90). Safety was favorable: no significant kidney or liver toxicity was reported, and hemoglobin levels remained stable. The only notable adverse effect was a statistically significant decrease in platelet count after retreatment (p=0.03). Patients who received two retreatment cycles had significantly longer PFS than those receiving one (p=0.014), and the presence of metastases before retreatment predicted shorter time to progression (p=0.04).
Silva, Maria Manuel; Canha, Marta; Salazar, Daniela; Neves, João Sergio; Ferreira, Gonçalo; Carvalho, Davide; Duarte, Hugo ·
RPEP-07394 · 2023This review synthesizes the entire SURPASS and SURMOUNT-1 clinical trial programs for tirzepatide. In type 2 diabetes (SURPASS), weekly tirzepatide 5-15 mg reduced HbA1c by 1.87-3.02% and body weight by 5.4-12.9 kg over up to 104 weeks, outperforming semaglutide 1 mg, dulaglutide, insulin degludec, and insulin glargine. It also improved liver fat, blood pressure, lipids, and reduced new-onset macroalbuminuria.
In obesity without diabetes (SURMOUNT-1), tirzepatide 5-15 mg produced 16.5-22.4% body weight reduction over 72 weeks — weight loss figures that were unprecedented at the time of publication.
Sinha, Rachel; Papamargaritis, Dimitris; Sargeant, Jack A; Davies, Melanie J · Review
RPEP-07395 · 2023The review identifies two categories of DNA effects from venom-derived compounds:
**Genotoxic effects (DNA damage):**
- Venom peptides like mastoparan, melectin, and melittin (from bee and wasp venoms) can bind DNA and produce DNA breaks
- Crude venoms from jellyfish, scorpions, spiders, and snakes cause DNA damage primarily through cell membrane disruption and subsequent oxidative stress
- Sponge-derived compounds (avarol, variolin B) and sea squirt-derived trabectedin also bind and damage DNA
**Genoprotective effects:**
- Certain animal venoms or their components produce protective effects against DNA damage
- The dual nature (damage vs protection) depends on concentration, target cell type, and specific compound
Both properties have therapeutic relevance — DNA-damaging ability could be harnessed for anti-cancer drugs, while protective effects could aid in preventing mutations.
Sjakste, Nikolajs; Gajski, Goran ·