This is a randomised double-blind placebo-controlled trial of L-serine in Hereditary Sensory Neuropathy type 1 (HSN1) due to variants in SPTLC1/2 gene.
This is a single-centre study being conducted at the National Hospital for Neurology and Neurosurgery, London UK.
The SENSE trial will test whether L-serine is an effective drug treatment to slow or stop disease progression in HSN1 due to variants in the SPLTLC1 or SPTLC2 gene. The other aim is to assess if Magnetic Resonance Imaging (MRI) can accurately detect the changes which occur in the muscles of people who have HSN1.

开始日期2023-08-21

申办/合作机构

University College London

ISRCTN17106427

/ Recruiting临床2期IIT

Randomised double blind placebo controlled trial of L-serine in Hereditary Sensory Neuropathy type 1

开始日期2023-08-01

申办/合作机构

University College London

100 项与 L-丝氨酸相关的临床结果

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100 项与 L-丝氨酸相关的转化医学

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100 项与 L-丝氨酸相关的专利（医药）

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100,037

项与 L-丝氨酸相关的文献（医药）

2025-12-31·Virulence

Staphylococcus aureus nt5 gene mutation through CRISPR RNA-guided base editing weakens bacterial virulence and immune evasion

Article

作者: Ye, Yang ; Xia, Zijing ; Wang, Haiyi ; Deng, Shi ; He, Fuqiang ; Dai, Ruiwu ; Liang, Shufang ; Liu, Xinpeng ; Huang, Lan ; Tang, Min ; Zhang, Peng

The resistance of commonly used clinical antibiotics, such as daptomycin (DAP), has become increasingly serious in the fight against Staphylococcus aureus (S. aureus) infection. It is essential to explore key pathogenicity-driven genes/proteins in bacterial infection and antibiotics resistance, which contributes to develop novel therapeutic strategies against S. aureus infections. The nt5 gene of S. aureus, encoding 5'-nucleotidase (NT5), is nearly unknown for its function in drug resistance and bacterial infection. Herein, to reveal nt5 gene role in drug resistance and infection ability of S. aureus, we performed nt5^C166T gene mutation using a clustered regulatory interspaced short palindromic repeat ribonucleic acid (RNA)-guided base editing system to investigate the lose-of-function of NT5 protein. Subsequent transcriptome sequencing of the mutant strain revealed that nt5 inactivation caused changes in cell membrane integrity and inhibited nucleotide metabolism, suggesting the nt5 gene may be involved in bacterial drug resistance and virulence. The mutant strain exhibited enhanced tolerance to DAP treatment by attenuating cell membrane potential dissipation and slowing deoxyribonucleic acid release. Moreover, the nt5 mutation alleviated abscess degree of mouse kidneys caused by S. aureus infection byreducing the expression of IL-1β, IL-6, and IL-18. The nt5 mutant strain was easily swallowed by host immune cells, resulting in weak bacterial toxicity of the S. aureus mutant in the bacterial infection process. In summary, nt5 gene mutation confers tolerance to DAP and a lower bacterial capacity to form kidney abscesses through phagocytosis of host immune cells, which indicates the targeted inhibition of NT5 protein would offer a potential new therapeutic strategy against S. aureus infection.

2025-09-01·Neural Regeneration Research

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

Article

作者: Kirov, Sergei A. ; Carretero, Victoria Jiménez ; Hernández-Campano, Jorge ; Álvarez-Merz, Iris ; Hernández-Guijo, Jesús M.

The involvement of the excitatory amino acids glutamate and aspartate in cerebral ischemia and excitotoxicity is well-documented. Nevertheless, the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied. The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra. Our findings indicated that the reversible loss of field excitatory postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids (L-alanine, glycine, L-glutamine, and L-serine) at their plasma concentrations. These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia, along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors. Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia. It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels, leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation. Thus, previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury. Understanding these pathways could highlight new therapeutic targets to mitigate brain injury.

2025-08-01·TALANTA

Glycopeptide-mimetic carbon dots/graphene oxide mediated fluorescent-recovery sensor for detecting Salmonella typhimurium

Article

作者: Wang, Xiaoying ; Lin, Zhenhao ; Wang, Xuan ; Cai, Jihai

Food safety issues associated with Salmonella present serious health risks, making detection crucial for public health protection. This study develops an efficient strategy for the capture of Salmonella typhimurium (S. typhimurium) based on the affinity between glycopeptide-mimetic carbon dots (g-CDs) and the type I fimbriae of S. typhimurium. The g-CDs were obtained by carbonizing mannose and histidine, which can be stored without light protection for over 90 days. Specially, the incorporation of histidine reduced the dissociation constant of g-CDs with lectin ConA from 135 μM to 25.4 μM. Further, g-CDs were anchored to phenylboronic acid-functionalized graphene oxide (GO-PBA) via dynamic borate bonds to create a fluorescent turn-on probe (CDs/GO-PBA). This probe exhibited a liner range of 10⁴-10⁷ CFU mL^-1, achieving 2370 CFU mL^-1 detection limit with a recovery rate ranging from 93 % to 103 % in chicken. The fluorescent sensor provides a promising strategy for the detection of S. typhimurium in food.

项与 L-丝氨酸相关的新闻（医药）

2022-08-23

·Science Daily

Surprising culprit worsens stroke, TBI damage

A new study provides for the first time the surprising evidence that four common nonexcitatory amino acids that usually make proteins which are essential to brain function, instead cause irreversible, destructive swelling of both the astrocytes that support neurons and the neurons themselves in the aftermath of stroke, TBI. In the aftermath of a stroke or TBI, a group of amino acids that typically support brain function contribute significantly to the brain destruction that can follow both these injuries, scientists report. The new study provides for the first time the surprising evidence that four common nonexcitatory amino acids that usually make proteins which are essential to brain function, instead cause irreversible, destructive swelling of both the astrocytes that support neurons and the neurons themselves, says Dr. Sergei Kirov, neuroscientist in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia. "There are many ways to kill neurons. This is one that people have not thought about," says Kirov, corresponding author of the study published in the journal GLIA. A stroke resulting from a ruptured or blocked blood vessel in the brain as well as traumatic brain injury, or TBI, both disrupt the uniquely, super-tightly woven endothelial cells that line blood vessels in the brain, which help ensure that nothing escapes from our blood that might hurt our brain. It's called the blood brain barrier and following these types of significant brain events, the protective barrier can become leaky and its components can escape. Plasma, the fluid part of the blood, is an early escapee into the already stressed nearby brain areas, and with it comes these amino acids, which make proteins, a fundamental component of our cells and muscle. Normally small molecules like oxygen are the ones that can pass through the blood brain barrier, and larger molecules like these amino acids, have a tightly regulated system that ensures that the right amount of the right factor gets delivered directly to the cells that need them. Transporters inside the membranes of the endothelial cells enable select items, including amino acids as well as glucose, to be delivered and may carry some other molecule out on the return trip. The most common excitatory amino acid glutamate, which as its descriptor implies excites neurons to action, is also delivered by transporters. Glutamate is a chemical messenger or neurotransmitter that binds to the NMDA receptor, which plays an important role in a myriad of key functions like learning and memory and breathing. One way it works is by activating channels that let things like calcium, sodium and potassium in but, as with most things in the body, too much activation of the receptor means too much calcium and sodium, followed by too much fluid, which is known to be lethal to neurons. The scientific team led by Kirov decided to look at the less-studied nonexcitatory amino acids. They used sophisticated technology including two photon laser microscopy that enables them to look real time into living tissue, in this case brain slices, and high-resolution images enabled by electron microscopy to directly examine the tissue for evidence of injury to astrocytes and neurons from four of these nonexcitatory amino acids: L-alanine, glycine, L-glutamine and L-serine, which are some of the most abundant in the plasma. Once the blood-brain barrier became leaky, the astrocytes and neurons became inundated with these amino acids. The brain cells literally overfilled with them, which, in turn, increased sodium inside cells. The sodium attracted water, so the expanded brain cells took up more space, which alone is dangerous in the closed confines of the skull. Astrocytes, accustomed to taking care of neurons, now tried to protect themselves by opening channels that allow excess water and molecules to escape. Glutamate also escaped at that point, which overstimulated the NMDA receptors, which overstimulated the neurons that can become injured, dramatically enlarged, burst and die, in a vicious, deadly circle. "We used electron microscopy to look at synapses where transmission happens and everything was messed up," says Kirov, who was very surprised by the amount of damage induced by the nonexcitatory amino acids. To confirm the surprising findings, they removed the nonexcitatory amino acids, and the ability of neurons to communicate was restored after 30 minutes of adequate oxygen, rather than the worsening damage that occurred when they were present. When they inhibited the NMDA receptors during hypoxia, the nonexcitatory amino acids again did not have the same deleterious impact. "No one was expecting these nonexcitatory amino acids would cause that much damage," Kirov reiterates. He anticipated that at the worst, the scientific team would find that the usual function of these amino acids would be wasted because the usual dynamic in the brain had been altered by a stroke or TBI. But their overt role in the destruction that resulted makes intervention in the vicious circle a clearly novel target in the destruction that follows a stroke or TBI, Kirov says. The transporters that move the amino acids may be a good first target, he says, with some sort of localized pharmacologic intervention to prevent or reduce their action in the immediate aftermath of a stroke or TBI. He notes that this new approach would likely be in conjunction with existing approaches that include, for example, surgical measures to reduce pressure inside the skull when it gets too high. Dr. Iris Álvarez-Merz, neuroscientist and the paper's first author, was a graduate student at the Universidad Aut?noma de Madrid, who worked with Kirov at MCG for several months and conducted the sophisticated testing that identified the resulting damage. She had some preliminary findings based on less sophisticated electrophysiology studies which look only at extracellular electrical activity, but more advanced techniques, like those available in Kirov's lab, were needed to make clear associations between the nonexcitatory amino acids and the brain damage that can follow stroke and TBI. Up to 90% of patients with these brain injuries experience collateral damage to brain tissue adjacent to the site of the injury, called the penumbra, hours and sometimes even days later, worsening damage and potential recovery prospects. Glutamate, the most abundant excitatory neurotransmitter, is normally recycled continuously by the body. Astrocytes convert it into glutamine, an amino acid, which is taken up by neurons which convert it back to glutamate. Too much glutamate is associated with neurodegenerative diseases like Alzheimer's and Parkinson's. The research was supported by the National Institutes of Health and the Spanish Ministerio de Ciencia, Innovacion y Universidades.

小分子药物

2021-07-06

·BioSpace

Clinical Catch-Up: June 28-July 2

It was another busy week for clinical trial news ahead of the July 4 holiday in the U.S. Here’s a look. COVID-19-Related Five pharmaceutical companies in India, Cipla, Dr Reddy, Emcure, Sun Pharma and Torrent Pharma, announced plans to collaborate on a clinical trial of the oral anti-viral drug molnupiravir for mild COVID-19 in an outpatient setting in India. Between March and April, the five companies entered into a non-exclusive voluntary licensing deal with Merck Sharp Dohme (MSD) [Merck, in the U.S.], to manufacture and distribute molnupiravir to India and more than 100 Low and Middle-Income Countries (LMICs). They have since entered into a deal to jointly sponsor, supervise and monitor the trial in India. It is expected to run between June and September with about 1,200 patients. The drug is being developed by Merck (MSD) via a collaboration with Ridgeback Biotherapeutics in a Phase III trial for non-hospitalized patients with confirmed COVID-19. Rigel Pharmaceuticals reported that its novel oral spleen tyrosine kinase (SYK) inhibitor, fostamatinib, had been chosen for a National Institutes of Health (NIH) ACTIV-4 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) trial in hospitalized COVID-19 patients. Funded by the National Heart, Lung, and Blood Institute (NHLBI) of the NIH and coordinated by Vanderbilt University Medical Center (VUMC), the trial is evaluating various treatments in hospitalized COVID-19 patients. ScandiBio Therapeutics published Phase III data showing that metabolic activators can decrease recovery time in patients with mild-to-moderate COVID-19. The study involved a collaboration between King’s College London and KTCH-Royal Institute of Technology. The trial included nicotinamide riboside (NR), L-serine, N-acetyl-L-cysteine (NAC), and L-carnitine tartrate. Altimmune provided an update on its AdCOVID investigational vaccine against COVID-19. The Phase I AdCOVID trial suggests the vaccine is well tolerated with an overall adverse event profile similar to intranasal saline placebo. The immunogenicity data was lower than expected, however. As a result, it is discontinuing further development beyond completing the Phase I trial. Angion Biomedica Corp. announced its Phase II ALI-201 trial of ANG-3777 in severe COVID-19-related pneumonia at high risk for ARDs failed to hit the primary or secondary efficacy endpoints. ANG-3777 is a small molecule mimic of the biological activity of hepatocyte growth factor (HGF), which activates the c-Met cascade of pathways involved in tissue and organ repair. CureVac reported final data for its COVID-19 vaccine, demonstrating 48% efficacy. It was a bit better at preventing symptomatic disease, at 53%, when the trial excluded people 60 years of age and older. In a June 16 readout, the figure was 47% overall. The company notes that the rise of more infectious variants has proven to be a headwind. The study involved approximately 40,000 adults in Europe and Latin America. A University of Oxford study found that a third shot of the AstraZeneca-Oxford COVID-19 vaccine created a strong immune response. The vaccine is typically dosed twice, usually four to 12 weeks apart. The study, which has yet to be peer reviewed, was in 90 trial participants in Britain who were the earliest to receive doses in 2020. In March 2021, they received a third dose, about 30 weeks after their second. The third dose increased levels of antibodies against SARS-CoV-2 higher than seen a month after the second dose. HDT Bio received the greenlight from the U.S. Food and Drug Administration (FDA) to proceed with a U.S.-based Phase I trial of its HDT-301 COVID-19 RNA vaccine. The vaccine is also designed to protect against variants. It will start enrolling 60 healthy volunteers this month and study the safety of two injections 28 days apart at three different dose levels. It will be open to unvaccinated and previously vaccinated people 18 to 65 years of age. Non-COVID-19-Related AstraZeneca reported positive results from the Phase III pivotal trial of exenatide extended-release 2mg once weekly for type 2 diabetes. The drug demonstrated significantly reduced blood sugar as measured by HbA1c compared to placebo in adolescents aged 10-17. Exenatide is a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA). Intellia Therapeutics and Regeneron Pharmaceuticals announced positive interim data from an ongoing Phase I trial of NTLA-2001 for transthyretin (ATTR) amyloidosis. NTLA-2001 is the first CRISPR/Cas9-based therapy candidate to be administered systemically, via IV infusion, for precision editing of a gene in a target tissue in humans. In this case, to inactive the TTR gene in liver cells to prevent the production of misfolded transthyretin (TTR) protein. Kite, a Gilead Company, announced top-line results from the primary analysis of its ZUMA-7 Phase III trial demonstrating superiority of Yescarta (axicabtagene ciloleucel) compared to standard of care (SOC) in second-line relapsed or refractory large B-cell lymphoma (LBCL). There was a median follow-up of two years, and it hit the primary endpoint of event-free survival (EFS). Eli Lilly published results from the SURPASS-1 trial showing that tirzepatide led to superior A1C and body weight reductions from baseline in all three doses in adults with type 2 diabetes. Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. Novo Nordisk presented data from its Phase IIIb SUSSAIN FORTE trial showing that 2 mg of Ozempic (semaglutide) injection provided statistically significant and superior reductions in blood sugar A1C compared to Ozempic 1 mg. Ozempic is a GLP-1 receptor agonist. Sanofi presented findings from the SoliMix study of Soliqua 100/33 (insulin glargine and lixisenatide injection) 100 Units/mL and 33 mcg/mL, iGlarLixi. The study hit its two primary endpoints and all key secondary endpoints in a head-to-head comparison against premixed insulin in adults with type 2 diabetes, uncontrolled on insulin and one or two oral anti-diabetic medicines. The primary endpoints were noninferiority of blood sugar reduction and superiority on body weight change from baseline compared to premixed insulin. Sanofi also presented positive topline results from the Phase II/III MEDLEY trial of nirsevimab compared to palivizumab when administered to preterm infants or those with chronic lung disease or congenital heart disease entering their first respiratory syncytial virus (RSV) season. Nirsevimab is an extended half-life RSV mAb. Sanofi also presented long-term safety data from a study of adults with moderate-to-severe atopic dermatitis in a Phase III trial that were treated with Dupixent. The data from the single-arm open label extension (OLE) trial demonstrated the long-term safety of the drug for up to three years, which was generally consistent to what was seen in the controlled pivotal Phase III trials. The data will be added to the Dupixent Summary of Product Characteristics (SmPC) after a positive opinion by the European Medicines Agency’s Committee for Medicinal Products for Human Use. ViaCyte presented preliminary data from its stem cell-derived islet cell replacement therapy for type 1 diabetes. The company’s PEC-Direct (VC-02) demonstrated effective engraftment and production of C-peptide, a biomarker for production of insulin by functional pancreatic beta cells. PEC-Direct is an islet cell replacement therapy made up of stem cell-derived pancreatic islet progenitor cells in a pouch that allows for direct vascularization of the implanted cells. Arrowhead Pharmaceuticals presented additional positive interim 48-week liver biopsy results from the ongoing AROAAT2002 study of ARO-AAT being co-developed with Takeda Pharmaceutical for alpha-1 antitrypsin deficiency (AATD). The drug is a second-generation RNA interference therapeutic. Denali Therapeutics began dosing in its Phase II trial of DNL758 for cutaneous lupus erythematosus (CLE). DNL858 is a peripherally-restricted small molecule inhibitor of RIPK1. Anavex Life Sciences reported that the predictive biomarker of response established with SIGMAR1 mRNA expression correlated significantly to responses in primary and secondary clinical efficacy endpoints from their Phase II trial in Parkinson’s disease dementia equally to target doses of 30mg, 50mg Anavex 2-73 or placebo, respectively. Amavex 2- 73 activates the sigma-1 receptor (SIGMAR1). Galera Therapeutics completed enrollment in its pivotal Phase III ROMAN trial of avasopasem manganese for severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (NHC) undergoing standard-of-care radiotherapy. Avasopasem is a selective small molecule dismutase mimetic. Transgene enrolled the first U.K. patient in the Phase I trial of TG4050. The company’s individualized cancer therapy is being evaluated in HPV-negative head and neck cancer. TG4050 is a vaccine based on the company’s myvac technology platform. Polyphor provided an updated on its Phase III FORTRESS trial of balixafortide in combination with eribulin for patients with HER2- locally recurrent or metastatic breast cancer. The trial did not meet its co-primary endpoint. Balixafortide is a specific and highly selective CXCR4 antagonist. AbbVie announced that its Phase III maintenance study of upadacitinib hit the primary endpoint of clinical remission and all secondary endpoints at one-year in ulcerative colitis. Upadacitinib is marketed under the name Rinvoq. It is a selective and reversible JAK inhibitor. Adocia launched a Phase I trial with McGill University (Canada) to assess BioChaperone Lispro Pramlintide (BC LisPram) prandial formulation in 16 people with type 1 diabetes compared to rapid insulin lispro. BioChaperone Lispo Pramlintide uses a single pump to deliver both hormones. Celularity announced expansion of its ongoing Phase I trial of CYNK-001 in acute myeloid leukemia to include patients with r/r/ AML along with its ongoing trial in patients with minimal residual disease (MRD). CYNK-001 is a placental-derived unmodified NK cell type. Cullinan Oncology received the greenlight from the FDA for a clinical trial of CLN-619 for both solid and liquid tumors. CLN-619 is a first-in-class monoclonal antibody that engages both NK and T-cell through the MICA/B-NKG2D axis. Elicio Therapeutics initiated a Phase I/II dose-escalation study of ELI-002 in KRAS-driven cancers. ELI-002 is the company’s therapeutic vaccine. Propella Therapeutics dosed the first patient in the Phase I/IIa trial of PRL-02 (abiraterone decanoate) for metastatic prostate cancer. PRL-02 is a next-generation androgen biosynthesis inhibitor, a patented prodrug of abiraterone designed for lymphatic targeting of tissues and tumors that express the CYP17 enzyme. BRIM Biotechnology has been given the go-ahead by the FDA to initiate a Phase III trial of BRM421 for Dry Eye Syndrome. The trial is expected to launch in 2022. BRIM421 is a first-in-class peptide derived from the company’s stem cell regenerative, Short Peptide (PDSP) technology platform. Precision BioSciences and SpringWorks Therapeutics dosed the first patient in its expanded Phase I/IIa trial of PBCAR269A with nirogacestat in r/r multiple myeloma. Nirogacestat is SpringWorks’ investigational gamma secretase inhibitor. Cerevel Therapeutics announced positive data from its Phase Ib trial of CVL-231 in adults with schizophrenia. The drug is a novel muscarinic M4-selective Positive Allosteric Modulator (PAM). The drug was generally well-tolerated and demonstrated clinically meaningful antipsychotic activity in both the 30 mg once-daily and 20 mg twice-daily doses. Iovance Biotherapeutics announced clinical results for its tumor infiltrating lymphocyte (TIL) therapy LN-145 in patients with metastatic non-small cell lung cancer (mNSCLC). The data was on patients enrolled in Cohort 3B of the ongoing basket study IOV-COM-202. These patients had progressed on previous checkpoint inhibitor therapy, including patients with oncogene-driven cancers who had received previous tyrosine kinase inhibitor (TKI) therapy. The overall response rate (ORR) was 21.4%, with one complete response and five partial responses. The disease control rate (DCR) was 64.3% after a single treatment. Median duration of response (MDR) was not reached at the median follow-up of 8.2 months. Alnylam Pharmaceuticals initiated its Phase II KARDIA-1 trial of zilebesiran for hypertension. The drug is a subcutaneous RNAi therapeutic targeting liver-expressed angiotensinogen (AGT). Axcella activated initial clinical sites and patient screenings for its Phase II trial of AXA1665 for recurrent overt hepatic encephalopathy (OHE). The drug is a multi-targeted oral candidate. It is a composition of eight amino acids and derivatives designed to target multiple metabolic pathways intersecting key organ systems, including the liver, muscle and gut. Histogen initiated its Phase I/II trial of HST 003 to regenerate hyaline cartilage in combination with a microfracture procedure. HST 003 is a human extracellular matrix implanted within microfracture interstices and the cartilage defect in the knee. Rafael Pharmaceuticals presented data on its Phase Ib/II trial of devimistat in pancreatic and biliary tract cancer. Devimistat is a first-in-class compound that targets enzymes involved in cancer cell energy metabolism located in the mitochondria of cancer cells. The company also announced positive preplanned interim futility analysis of the ARMADA 2000 Phase III trial of devimistat for r/r acute myeloid leukemia. It was found to be non-futile and the committee recommended continuing the trial as is. Saniona dosed the first patient in its Phase I trial of SAN711 for rare neuropathic disorders. The drug is a first-in-class positive allosteric modulator of GABA-A alpha3 receptors. Initially it has been tested in models of neuropathic pain. Ocuphire Pharma announced the VEGA-1 Phase II trial of Nyxol in combination with low-dose pilocarpine (LDP) in presbyopic subjects hit its primary and many secondary endpoints. Presbyopia is far-sightedness. Sanaria published data from its Phase I trial of PfSPZ-CVac (CQ) vaccine against malaria. In six subjects, it protected 100% against a variant malaria parasite three months after their last dose of the vaccine. The variant parasite used is a Brazilian malaria parasite genetically more variant from the African parasites. Brickell Biotech indicated the final patient had completed the Phase III Cardigan I study of sofpironium bromide gel, 15% for primary axillary hyperhidrosis. Also, all planned patients have been enrolled in the Phase III Cardigan II study. Axillary hyperhidrosis is extreme sweating of the underarm. GenSight Biologics reported topline results from the REFLECT Phase III trial of Lumevoq (lenadogene nolparvovec) in vision loss due to Leber Hereditary Optic Neuropathy (LHON) caused by a mutated ND4 mitochondrial gene. The study showed data at 1.5 years post-treatment, demonstrating better visual acuity improvements from bilateral intravitreal injections of the gene therapy compared to a unilateral injection. Aileron Therapeutics initiated a Phase Ib trial of ALRN-6924 in advanced non-small cell lung cancer (NSCLC). The trial will enroll 60 patients with advanced p53-mutated NSCLC undergoing chemotherapy with first-line carboplatin plus pemetrexed. ALRN-6924 is designed to selectively protect healthy cells in patients with cancers that harbor p53 mutations to decrease or eliminate chemotherapy-induced side effects. Sequana Medical announced positive results from the second interim analysis of the POSEIDON Phase III study of the alfapump for recurrent or refractory ascites due to liver cirrhosis. The data in the Roll-In Cohort are consistent with the previous interim data, including positive outcomes against all primary endpoints and a rapid and persistent clinically important improvement in quality-of-life measures. They expect to add another 10 patients in the Pivotal Cohort based on the analysis of attrition between study enrollment and alfapump implantation. Alfapump is a fully implanted wireless device that automatically pumps fluid from the abdominal cavity into the bladder, where it is naturally eliminated through urination.

疫苗基因疗法抗体First in Class小分子药物

2021-07-02

·BioSpace

Clinical Catch-Up: June 28-July 2

It was another busy week for clinical trial news ahead of the July 4 holiday in the U.S. Here’s a look. It was another busy week for clinical trial news ahead of the July 4 holiday in the U.S. Here’s a look. COVID-19-Related Five pharmaceutical companies in India, Cipla, Dr Reddy, Emcure, Sun Pharma and Torrent Pharma, announced plans to collaborate on a clinical trial of the oral anti-viral drug molnupiravir for mild COVID-19 in an outpatient setting in India. Between March and April, the five companies entered into a non-exclusive voluntary licensing deal with Merck Sharp Dohme (MSD) [Merck, in the U.S.], to manufacture and distribute molnupiravir to India and more than 100 Low and Middle-Income Countries (LMICs). They have since entered into a deal to jointly sponsor, supervise and monitor the trial in India. It is expected to run between June and September with about 1,200 patients. The drug is being developed by Merck (MSD) via a collaboration with Ridgeback Biotherapeutics in a Phase III trial for non-hospitalized patients with confirmed COVID-19. Rigel Pharmaceuticals reported that its novel oral spleen tyrosine kinase (SYK) inhibitor, fostamatinib, had been chosen for a National Institutes of Health (NIH) ACTIV-4 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) trial in hospitalized COVID-19 patients. Funded by the National Heart, Lung, and Blood Institute (NHLBI) of the NIH and coordinated by Vanderbilt University Medical Center (VUMC), the trial is evaluating various treatments in hospitalized COVID-19 patients. ScandiBio Therapeutics published Phase III data showing that metabolic activators can decrease recovery time in patients with mild-to-moderate COVID-19. The study involved a collaboration between King’s College London and KTCH-Royal Institute of Technology. The trial included nicotinamide riboside (NR), L-serine, N-acetyl-L-cysteine (NAC), and L-carnitine tartrate. Altimmune provided an update on its AdCOVID investigational vaccine against COVID-19. The Phase I AdCOVID trial suggests the vaccine is well tolerated with an overall adverse event pro to intranasal saline placebo. The immunogenicity data was lower than expected, however. As a result, it is discontinuing further development beyond completing the Phase I trial. Angion Biomedica Corp. announced its Phase II ALI-201 trial of ANG-3777 in severe COVID-19-related pneumonia at high risk for ARDs failed to hit the primary or secondary efficacy endpoints. ANG-3777 is a small molecule mimic of the biological activity of hepatocyte growth factor (HGF), which activates the c-Met cascade of pathways involved in tissue and organ repair. CureVac reported final data for its COVID-19 vaccine, demonstrating 48% efficacy. It was a bit better at preventing symptomatic disease, at 53%, when the trial excluded people 60 years of age and older. In a June 16 readout, the figure was 47% overall. The company notes that the rise of more infectious variants has proven to be a headwind. The study involved approximately 40,000 adults in Europe and Latin America. A University of Oxford study found that a third shot of the AstraZeneca-Oxford COVID-19 vaccine created a strong immune response. The vaccine is typically dosed twice, usually four to 12 weeks apart. The study, which has yet to be peer reviewed, was in 90 trial participants in Britain who were the earliest to receive doses in 2020. In March 2021, they received a third dose, about 30 weeks after their second. The third dose increased levels of antibodies against SARS-CoV-2 higher than seen a month after the second dose. HDT Bio received the greenlight from the U.S. Food and Drug Administration (FDA) to proceed with a U.S.-based Phase I trial of its HDT-301 COVID-19 RNA vaccine. The vaccine is also designed to protect against variants. It will start enrolling 60 healthy volunteers this month and study the safety of two injections 28 days apart at three different dose levels. It will be open to unvaccinated and previously vaccinated people 18 to 65 years of age. Non-COVID-19-Related AstraZeneca reported positive results from the Phase III pivotal trial of exenatide extended-release 2mg once weekly for type 2 diabetes. The drug demonstrated significantly reduced blood sugar as measured by HbA1c compared to placebo in adolescents aged 10-17. Exenatide is a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA). Intellia Therapeutics and Regeneron Pharmaceuticals announced positive interim data from an ongoing Phase I trial of NTLA-2001 for transthyretin (ATTR) amyloidosis. NTLA-2001 is the first CRISPR/Cas9-based therapy candidate to be administered systemically, via IV infusion, for precision editing of a gene in a target tissue in humans. In this case, to inactive the TTR gene in liver cells to prevent the production of misfolded transthyretin (TTR) protein. Kite , a Gilead Company, announced top-line results from the primary analysis of its ZUMA-7 Phase III trial demonstrating superiority of Yescarta (axicabtagene ciloleucel) compared to standard of care (SOC) in second-line relapsed or refractory large B-cell lymphoma (LBCL). There was a median follow-up of two years, and it hit the primary endpoint of event-free survival (EFS). Eli Lilly published results from the SURPASS-1 trial showing that tirzepatide led to superior A1C and body weight reductions from baseline in all three doses in adults with type 2 diabetes. Tirzepatide is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. Novo Nordisk presented data from its Phase IIIb SUSSAIN FORTE trial showing that 2 mg of Ozempic (semaglutide) injection provided statistically significant and superior reductions in blood sugar A1C compared to Ozempic 1 mg. Ozempic is a GLP-1 receptor agonist. Sanofi presented findings from the SoliMix study of Soliqua 100/33 (insulin glargine and lixisenatide injection) 100 Units/mL and 33 mcg/mL, iGlarLixi. The study hit its two primary endpoints and all key secondary endpoints in a head-to-head comparison against premixed insulin in adults with type 2 diabetes, uncontrolled on insulin and one or two oral anti-diabetic medicines. The primary endpoints were noninferiority of blood sugar reduction and superiority on body weight change from baseline compared to premixed insulin. Sanofi also presented positive topline results from the Phase II/III MEDLEY trial of nirsevimab compared to palivizumab when administered to preterm infants or those with chronic lung disease or congenital heart disease entering their first respiratory syncytial virus (RSV) season. Nirsevimab is an extended half-life RSV mAb. Sanofi also presented long-term safety data from a study of adults with moderate-to-severe atopic dermatitis in a Phase III trial that were treated with Dupixent. The data from the single-arm open label extension (OLE) trial demonstrated the long-term safety of the drug for up to three years, which was generally consistent to what was seen in the controlled pivotal Phase III trials. The data will be added to the Dupixent Summary of Product Characteristics (SmPC) after a positive opinion by the European Medicines Agency’s Committee for Medicinal Products for Human Use. ViaCyte presented preliminary data from its stem cell-derived islet cell replacement therapy for type 1 diabetes. The company’s PEC-Direct (VC-02) demonstrated effective engraftment and production of C-peptide, a biomarker for production of insulin by functional pancreatic beta cells. PEC-Direct is an islet cell replacement therapy made up of stem cell-derived pancreatic islet progenitor cells in a pouch that allows for direct vascularization of the implanted cells. Arrowhead Pharmaceuticals presented additional positive interim 48-week liver biopsy results from the ongoing AROAAT2002 study of ARO-AAT being co-developed with Takeda Pharmaceutical for alpha-1 antitrypsin deficiency (AATD). The drug is a second-generation RNA interference therapeutic. Denali Therapeutics began dosing in its Phase II trial of DNL758 for cutaneous lupus erythematosus (CLE). DNL858 is a peripherally-restricted small molecule inhibitor of RIPK1. Anavex Life Sciences reported that the predictive biomarker of response established with SIGMAR1 mRNA expression correlated significantly to responses in primary and secondary clinical efficacy endpoints from their Phase II trial in Parkinson’s disease dementia equally to target doses of 30mg, 50mg Anavex 2-73 or placebo, respectively. Amavex 2- 73 activates the sigma-1 receptor (SIGMAR1). Galera Therapeutics completed enrollment in its pivotal Phase III ROMAN trial of avasopasem manganese for severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (NHC) undergoing standard-of-care radiotherapy. Avasopasem is a selective small molecule dismutase mimetic. Transgene enrolled the first U.K. patient in the Phase I trial of TG4050. The company’s individualized cancer therapy is being evaluated in HPV-negative head and neck cancer. TG4050 is a vaccine based on the company’s myvac technology platform. Polyphor provided an updated on its Phase III FORTRESS trial of balixafortide in combination with eribulin for patients with HER2- locally recurrent or metastatic breast cancer. The trial did not meet its co-primary endpoint. Balixafortide is a specific and highly selective CXCR4 antagonist. AbbVie announced that its Phase III maintenance study of upadacitinib hit the primary endpoint of clinical remission and all secondary endpoints at one-year in ulcerative colitis. Upadacitinib is marketed under the name Rinvoq. It is a selective and reversible JAK inhibitor. Adocia launched a Phase I trial with McGill University (Canada) to assess BioChaperone Lispro Pramlintide (BC LisPram) prandial formulation in 16 people with type 1 diabetes compared to rapid insulin lispro. BioChaperone Lispo Pramlintide uses a single pump to deliver both hormones. Celularity announced expansion of its ongoing Phase I trial of CYNK-001 in acute myeloid leukemia to include patients with r/r/ AML along with its ongoing trial in patients with minimal residual disease (MRD). CYNK-001 is a placental-derived unmodified NK cell type. Cullinan Oncology received the greenlight from the FDA for a clinical trial of CLN-619 for both solid and liquid tumors. CLN-619 is a first-in-class monoclonal antibody that engages both NK and T-cell through the MICA/B-NKG2D axis. Elicio Therapeutics initiated a Phase I/II dose-escalation study of ELI-002 in KRAS-driven cancers. ELI-002 is the company’s therapeutic vaccine. Propella Therapeutics dosed the first patient in the Phase I/IIa trial of PRL-02 (abiraterone decanoate) for metastatic prostate cancer. PRL-02 is a next-generation androgen biosynthesis inhibitor, a patented prodrug of abiraterone designed for lymphatic targeting of tissues and tumors that express the CYP17 enzyme. BRIM Biotechnology has been given the go-ahead by the FDA to initiate a Phase III trial of BRM421 for Dry Eye Syndrome. The trial is expected to launch in 2022. BRIM421 is a first-in-class peptide derived from the company’s stem cell regenerative, Short Peptide (PDSP) technology platform. Precision BioSciences and SpringWorks Therapeutics dosed the first patient in its expanded Phase I/IIa trial of PBCAR269A with nirogacestat in r/r multiple myeloma. Nirogacestat is SpringWorks’ investigational gamma secretase inhibitor. Cerevel Therapeutics announced positive data from its Phase Ib trial of CVL-231 in adults with schizophrenia. The drug is a novel muscarinic M4-selective Positive Allosteric Modulator (PAM). The drug was generally well-tolerated and demonstrated clinically meaningful antipsychotic activity in both the 30 mg once-daily and 20 mg twice-daily doses. Iovance Biotherapeutics announced clinical results for its tumor infiltrating lymphocyte (TIL) therapy LN-145 in patients with metastatic non-small cell lung cancer (mNSCLC). The data was on patients enrolled in Cohort 3B of the ongoing basket study IOV-COM-202. These patients had progressed on previous checkpoint inhibitor therapy, including patients with oncogene-driven cancers who had received previous tyrosine kinase inhibitor (TKI) therapy. The overall response rate (ORR) was 21.4%, with one complete response and five partial responses. The disease control rate (DCR) was 64.3% after a single treatment. Median duration of response (MDR) was not reached at the median follow-up of 8.2 months. Alnylam Pharmaceuticals initiated its Phase II KARDIA-1 trial of zilebesiran for hypertension. The drug is a subcutaneous RNAi therapeutic targeting liver-expressed angiotensinogen (AGT). Axcella activated initial clinical sites and patient screenings for its Phase II trial of AXA1665 for recurrent overt hepatic encephalopathy (OHE). The drug is a multi-targeted oral candidate. It is a composition of eight amino acids and derivatives designed to target multiple metabolic pathways intersecting key organ systems, including the liver, muscle and gut. Histogen initiated its Phase I/II trial of HST 003 to regenerate hyaline cartilage in combination with a microfracture procedure. HST 003 is a human extracellular matrix implanted within microfracture interstices and the cartilage defect in the knee. Rafael Pharmaceuticals presented data on its Phase Ib/II trial of devimistat in pancreatic and biliary tract cancer. Devimistat is a first-in-class compound that targets enzymes involved in cancer cell energy metabolism located in the mitochondria of cancer cells. The company also announced positive preplanned interim futility analysis of the ARMADA 2000 Phase III trial of devimistat for r/r acute myeloid leukemia. It was found to be non-futile and the committee recommended continuing the trial as is. Saniona dosed the first patient in its Phase I trial of SAN711 for rare neuropathic disorders. The drug is a first-in-class positive allosteric modulator of GABA-A alpha3 receptors. Initially it has been tested in models of neuropathic pain. Ocuphire Pharma announced the VEGA-1 Phase II trial of Nyxol in combination with low-dose pilocarpine (LDP) in presbyopic subjects hit its primary and many secondary endpoints. Presbyopia is far-sightedness. Sanaria published data from its Phase I trial of PfSPZ-CVac (CQ) vaccine against malaria. In six subjects, it protected 100% against a variant malaria parasite three months after their last dose of the vaccine. The variant parasite used is a Brazilian malaria parasite genetically more variant from the African parasites. Brickell Biotech indicated the final patient had completed the Phase III Cardigan I study of sofpironium bromide gel, 15% for primary axillary hyperhidrosis. Also, all planned patients have been enrolled in the Phase III Cardigan II study. Axillary hyperhidrosis is extreme sweating of the underarm. GenSight Biologics reported topline results from the REFLECT Phase III trial of Lumevoq (lenadogene nolparvovec) in vision loss due to Leber Hereditary Optic Neuropathy (LHON) caused by a mutated ND4 mitochondrial gene. The study showed data at 1.5 years post-treatment, demonstrating better visual acuity improvements from bilateral intravitreal injections of the gene therapy compared to a unilateral injection. Aileron Therapeutics initiated a Phase Ib trial of ALRN-6924 in advanced non-small cell lung cancer (NSCLC). The trial will enroll 60 patients with advanced p53-mutated NSCLC undergoing chemotherapy with first-line carboplatin plus pemetrexed. ALRN-6924 is designed to selectively protect healthy cells in patients with cancers that harbor p53 mutations to decrease or eliminate chemotherapy-induced side effects. Sequana Medical announced positive results from the second interim analysis of the POSEIDON Phase III study of the alfapump for recurrent or refractory ascites due to liver cirrhosis. The data in the Roll-In Cohort are consistent with the previous interim data, including positive outcomes against all primary endpoints and a rapid and persistent clinically important improvement in quality-of-life measures. They expect to add another 10 patients in the Pivotal Cohort based on the analysis of attrition between study enrollment and alfapump implantation. Alfapump is a fully implanted wireless device that automatically pumps fluid from the abdominal cavity into the bladder, where it is naturally eliminated through urination.

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KEGG	Wiki	ATC	Drug Bank
-	L-丝氨酸	-	DB00133

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适应症	最高研发状态	国家/地区	公司	日期
终板乙酰胆碱酯酶缺乏症	临床2期	美国	Dartmouth-Hitchcock Medical Center	2017-03-01
心血管疾病	临床2期	瑞典	Sahlgrenska Universitetssjukhuset	2015-10-31
2型糖尿病	临床2期	瑞典	Sahlgrenska Universitetssjukhuset	2015-10-31
酒精性脂肪肝病	临床2期	瑞典	Sahlgrenska Universitetssjukhuset	2015-10-31
纤维化	临床2期	瑞典	Sahlgrenska Universitetssjukhuset	2015-10-31
非酒精性脂肪性肝炎	临床2期	瑞典	Sahlgrenska Universitetssjukhuset	2015-10-31
肥胖	临床2期	瑞典	Sahlgrenska Universitetssjukhuset	2015-10-31
遗传性感觉和自主神经性神经病	临床2期	美国	The General Hospital Corp.	2013-09-01
阿尔茨海默症	临床2期	美国	Phoenix Neurological Associates Ltd.	2013-01-31
帕金森病	临床2期	美国	Phoenix Neurological Associates Ltd.	2013-01-31

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03062449 (LSPI-2, CTgov)	临床2期	终板乙酰胆碱酯酶缺乏症 \| 阿尔茨海默症	29	L-serine (L-Serine Gummy Arm)	鑰餘築網製顧願襯衊獵(觸選憲鏇憲顧築餘齋鑰) = 夢窪鑰齋膚壓齋築齋鑰餘膚簾壓選範齋鹹簾築 (構鹽鏇範觸願築衊鹹壓, 觸壓製窪衊鹽鏇蓋淵簾 ~ 選鬱淵選鏇鹽夢繭願構) 更多	-	2024-07-03
				Placebo Gummy (Placebo Gummy Arm)	鑰餘築網製顧願襯衊獵(觸選憲鏇憲顧築餘齋鑰) = 蓋襯膚餘膚鹽襯鹹積觸餘膚簾壓選範齋鹹簾築 (構鹽鏇範觸願築衊鹹壓, 夢襯糧糧顧繭艱繭選選 ~ 範範製構齋選廠膚襯壓) 更多
NCT01733407 (Pubmed \| Neurology)	临床1/2期	遗传性感觉和自主神经性神经病	18	l-serine	夢築鹽選獵衊獵夢憲艱(選網顧顧鹽網簾蓋鏇夢) = 構獵齋鬱鏇鏇齋遞鏇網觸獵範遞鏇鑰網範製艱 (鹽夢襯蓋夢網膚鑰艱蓋, -2.8 ~ -0.1)	积极	2019-01-22
NCT01733407 (CTgov)	临床1/2期	遗传性感觉和自主神经性神经病	18	placebo (Sugar Pill)	遞壓襯鏇製壓鹽鹹鬱網(醖選構積築觸網鏇鹽網) = 鏇觸壓鏇壓積顧齋廠鬱鬱醖構築餘糧範衊醖構 (淵製積獵憲遞願獵鏇窪, 6.69) 更多	-	2018-09-12
				L-serine (L-serine)	遞壓襯鏇製壓鹽鹹鬱網(醖選構積築觸網鏇鹽網) = 淵繭鑰糧鏇簾襯餘淵鹽鬱醖構築餘糧範衊醖構 (淵製積獵憲遞願獵鏇窪, 10.10) 更多
AAN2017	N/A	遗传性感觉和自主神经性神经病 1-deoxysphingolipids (1-deoxySL)	-	L-serine	醖鏇鏇遞壓夢襯顧構糧(鹹憲網願艱膚選範構構) = 簾襯壓觸鹽淵糧築選鑰鏇蓋衊鏇鹹積齋廠鑰衊 (壓窪願鏇鏇膚製範築淵 ) 更多	积极	2017-04-18
				Placebo	醖鏇鏇遞壓夢襯顧構糧(鹹憲網願艱膚選範構構) = 廠願膚壓憲願遞顧襯製鏇蓋衊鏇鹹積齋廠鑰衊 (壓窪願鏇鏇膚製範築淵 )
NIH R15DC005962 (SFN2004)	N/A	-	-	L-Serine	鬱選艱鹽觸顧繭衊顧鬱(繭願鑰膚壓襯餘襯鹽構) = 獵願膚構襯觸襯鹹鏇襯鏇製餘鹽獵構鏇網餘窪 (遞餘獵遞餘壓獵夢廠繭 )	-	2004-10-25
				L-serine (MSG)	鬱選艱鹽觸顧繭衊顧鬱(繭願鑰膚壓襯餘襯鹽構) = 膚築醖鬱憲築齋艱淵製鏇製餘鹽獵構鏇網餘窪 (遞餘獵遞餘壓獵夢廠繭 )