Protein replacement therapies for rare diseases: a breeze for regulatory approval?

abstract：:Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we i...

journal_title：Science translational medicine

authors： Muenchhoff M,Adland E,Karimanzira O,Crowther C,Pace M,Csala A,Leitman E,Moonsamy A,McGregor C,Hurst J,Groll A,Mori M,Sinmyee S,Thobakgale C,Tudor-Williams G,Prendergast AJ,Kloverpris H,Roider J,Leslie A,Shingadia D

更新日期：2016-09-28 00:00:00

abstract：:Lung cancer is more deadly than colon, breast, and prostate cancers combined, and treatment improvements have failed to improve prognosis significantly. Here, we identify a critical mediator of lung cancer progression, Rac1b, a tumor-associated protein with cell-transforming properties that are linked to the matrix me...

journal_title：Science translational medicine

authors： Stallings-Mann ML,Waldmann J,Zhang Y,Miller E,Gauthier ML,Visscher DW,Downey GP,Radisky ES,Fields AP,Radisky DC

更新日期：2012-07-11 00:00:00

abstract：:KRAS represents an excellent therapeutic target in lung cancer, the most commonly mutated form of which can now be blocked using KRAS-G12C mutant-specific inhibitory trial drugs. Lung adenocarcinoma cells harboring KRAS mutations have been shown previously to be selectively sensitive to inhibition of mitogen-activated...

journal_title：Science translational medicine

authors： Molina-Arcas M,Moore C,Rana S,van Maldegem F,Mugarza E,Romero-Clavijo P,Herbert E,Horswell S,Li LS,Janes MR,Hancock DC,Downward J

更新日期：2019-09-18 00:00:00

abstract：:Neuroinflammation has been increasingly recognized to play a critical role in Alzheimer's disease (AD). The epoxy fatty acids (EpFAs) are derivatives of the arachidonic acid metabolism pathway and have anti-inflammatory activities. However, their efficacy is limited because of their rapid hydrolysis by the soluble epo...

journal_title：Science translational medicine

authors： Ghosh A,Comerota MM,Wan D,Chen F,Propson NE,Hwang SH,Hammock BD,Zheng H

更新日期：2020-12-09 00:00:00

abstract：:Medical devices and implants made of synthetic materials can induce an immune-mediated process when implanted in the body called the foreign body response, which results in formation of a fibrous capsule around the implant. To explore the immune and stromal connections underpinning the foreign body response, we analyz...

journal_title：Science translational medicine

authors： Chung L,Maestas DR Jr,Lebid A,Mageau A,Rosson GD,Wu X,Wolf MT,Tam AJ,Vanderzee I,Wang X,Andorko JI,Zhang H,Narain R,Sadtler K,Fan H,Čiháková D,Le Saux CJ,Housseau F,Pardoll DM,Elisseeff JH

更新日期：2020-04-15 00:00:00

abstract：:Bactericidal antibiotics with diverse mechanisms of action induce generation of mitochondrial reactive oxygen species in mammalian cells (Kalghatgi et al., this issue). ...

journal_title：Science translational medicine

authors： Chandel NS,Budinger GR

更新日期：2013-07-03 00:00:00

abstract：:Age is the most significant risk factor for atherosclerosis; however, the link between age and atherosclerosis is poorly understood. During both aging and atherosclerosis progression, the blood vessel wall stiffens owing to alterations in the extracellular matrix. Using in vitro and ex vivo models of vessel wall stiff...

journal_title：Science translational medicine

authors： Huynh J,Nishimura N,Rana K,Peloquin JM,Califano JP,Montague CR,King MR,Schaffer CB,Reinhart-King CA

更新日期：2011-12-07 00:00:00

abstract：:Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth ag...

journal_title：Science translational medicine

authors： Julg B,Tartaglia LJ,Keele BF,Wagh K,Pegu A,Sok D,Abbink P,Schmidt SD,Wang K,Chen X,Joyce MG,Georgiev IS,Choe M,Kwong PD,Doria-Rose NA,Le K,Louder MK,Bailer RT,Moore PL,Korber B,Seaman MS,Abdool Karim SS,Morris

更新日期：2017-09-06 00:00:00

abstract：:Sleep disorders are highly prevalent in patients with traumatic brain injury (TBI) and can significantly impair cognitive rehabilitation. No proven therapies exist to mitigate the neurocognitive consequences of TBI. We show that mild brain injury in mice causes a persistent inability to maintain wakefulness and decrea...

journal_title：Science translational medicine

authors： Lim MM,Elkind J,Xiong G,Galante R,Zhu J,Zhang L,Lian J,Rodin J,Kuzma NN,Pack AI,Cohen AS

更新日期：2013-12-11 00:00:00

abstract：:Physiologically relevant ALK (anaplastic lymphoma kinase) expression was not detected in human and mouse monocytes and macrophages, suggesting that the effects of bioactive compounds on stimulator of interferon genes (STING) activation may not depend on ALK. ...

journal_title：Science translational medicine

authors： Blasco RB,Patrucco E,Mota I,Tai WT,Chiarle R

更新日期：2018-12-12 00:00:00

abstract：:Targeting androgen receptor (AR) axis signaling by disrupting androgen-AR interactions remains the primary treatment for metastatic prostate cancer. Unfortunately, all men develop resistance to primary castrating therapy and secondary androgen deprivation therapies (ADTs). Resistance develops in part because castratio...

journal_title：Science translational medicine

authors： Schweizer MT,Antonarakis ES,Wang H,Ajiboye AS,Spitz A,Cao H,Luo J,Haffner MC,Yegnasubramanian S,Carducci MA,Eisenberger MA,Isaacs JT,Denmeade SR

更新日期：2015-01-07 00:00:00

abstract：:Elevated serum levels of both total and allergen-specific immunoglobulin E (IgE) correlate with atopic diseases such as allergic rhinitis and allergic asthma. Neutralization of IgE by anti-IgE antibodies can effectively treat allergic asthma. Preclinical studies indicate that targeting membrane IgE-positive cells with...

journal_title：Science translational medicine

authors： Gauvreau GM,Harris JM,Boulet LP,Scheerens H,Fitzgerald JM,Putnam WS,Cockcroft DW,Davis BE,Leigh R,Zheng Y,Dahlén B,Wang Y,Maciuca R,Mayers I,Liao XC,Wu LC,Matthews JG,O'Byrne PM

更新日期：2014-07-02 00:00:00

abstract：:Treatment of life-threatening Epstein-Barr virus (EBV)-associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating re...

journal_title：Science translational medicine

authors： Wang X,Xiang Z,Liu Y,Huang C,Pei Y,Wang X,Zhi H,Wong WH,Wei H,Ng IO,Lee PP,Chan GC,Lau YL,Tu W

更新日期：2020-09-30 00:00:00

abstract：:Interpandemic or seasonal influenza A, currently subtypes H3N2 and H1N1, exacts an enormous annual burden both in terms of human health and economic impact. Incidence prediction ahead of season remains a challenge largely because of the virus' antigenic evolution. We propose a forecasting approach that incorporates ev...

journal_title：Science translational medicine

authors： Du X,King AA,Woods RJ,Pascual M

更新日期：2017-10-25 00:00:00

abstract：:Migraine-related photophobia is multifaceted and may be mediated by numerous pathways. ...

journal_title：Science translational medicine

authors： Lehtinen MK

更新日期：2017-07-12 00:00:00

abstract：:Preexisting lymphocytic infiltration of tumors is associated with superior prognostic outcomes in a variety of cancers. Recent studies also suggest that lymphocytic responses may identify patients more likely to benefit from therapies targeting immune checkpoints, suggesting that therapeutic efficacy of immune checkpo...

journal_title：Science translational medicine

authors： Zamarin D,Holmgaard RB,Subudhi SK,Park JS,Mansour M,Palese P,Merghoub T,Wolchok JD,Allison JP

更新日期：2014-03-05 00:00:00

abstract：:Forty years ago, Judah Folkman predicted that tumor growth is dependent on angiogenesis and that inhibiting this process might be a new strategy for cancer therapy. This hypothesis formed the foundation of a new field of research that represents an excellent example of how a groundbreaking scientific discovery can be ...

journal_title：Science translational medicine

authors： Cao Y,Arbiser J,D'Amato RJ,D'Amore PA,Ingber DE,Kerbel R,Klagsbrun M,Lim S,Moses MA,Zetter B,Dvorak H,Langer R

更新日期：2011-12-21 00:00:00

abstract：:Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for year...

journal_title：Science translational medicine

authors： Moon JH,Kim H,Kim H,Park J,Choi W,Choi W,Hong HJ,Ro HJ,Jun S,Choi SH,Banerjee RR,Shong M,Cho NH,Kim SK,German MS,Jang HC,Kim H

更新日期：2020-04-29 00:00:00

abstract：:We tested the hypothesis that ex vivo hepatocyte gene therapy can correct the metabolic disorder in fumarylacetoacetate hydrolase-deficient (Fah(-/-)) pigs, a large animal model of hereditary tyrosinemia type 1 (HT1). Recipient Fah(-/-) pigs underwent partial liver resection and hepatocyte isolation by collagenase dig...

journal_title：Science translational medicine

authors： Hickey RD,Mao SA,Glorioso J,Elgilani F,Amiot B,Chen H,Rinaldo P,Marler R,Jiang H,DeGrado TR,Suksanpaisan L,O'Connor MK,Freeman BL,Ibrahim SH,Peng KW,Harding CO,Ho CS,Grompe M,Ikeda Y,Lillegard JB,Russell SJ,Nybe

更新日期：2016-07-27 00:00:00

abstract：:Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imagin...

journal_title：Science translational medicine

authors： Ordonez AA,Sellmyer MA,Gowrishankar G,Ruiz-Bedoya CA,Tucker EW,Palestro CJ,Hammoud DA,Jain SK

更新日期：2019-09-04 00:00:00

abstract：:Each year, more than a half million people in the United States alone die from sepsis, a dire multisystem disease with highly inadequate treatment options. In a recent issue of Science, Puneet and colleagues provide compelling evidence that inhibiting sphingosine kinase 1--an enzyme that resides in immune cells and is...

journal_title：Science translational medicine

authors： O'Neill LA

更新日期：2010-06-16 00:00:00

abstract：:Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, wher...

journal_title：Science translational medicine

authors： Lionello VM,Nicot AS,Sartori M,Kretz C,Kessler P,Buono S,Djerroud S,Messaddeq N,Koebel P,Prokic I,Hérault Y,Romero NB,Laporte J,Cowling BS

更新日期：2019-03-20 00:00:00

abstract：:Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacok...

journal_title：Science translational medicine

authors： Andrews CD,Yueh YL,Spreen WR,St Bernard L,Boente-Carrera M,Rodriguez K,Gettie A,Russell-Lodrigue K,Blanchard J,Ford S,Mohri H,Cheng-Mayer C,Hong Z,Ho DD,Markowitz M

更新日期：2015-01-14 00:00:00

abstract：:There is a critical need for effective new pharmacotherapies for pain. The paucity of new drugs successfully reaching the clinic calls for a reassessment of current analgesic drug discovery approaches. Many points early in the discovery process present significant hurdles, making it critical to exploit advances in pai...

journal_title：Science translational medicine

authors： Borsook D,Hargreaves R,Bountra C,Porreca F

更新日期：2014-08-13 00:00:00

abstract：:Aspirin use reduces the risk of colorectal neoplasia, at least in part, through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2)-related pathways. Hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (15-PGDH, HPGD) is down-regulated in colorectal cancers and functions...

journal_title：Science translational medicine

authors： Fink SP,Yamauchi M,Nishihara R,Jung S,Kuchiba A,Wu K,Cho E,Giovannucci E,Fuchs CS,Ogino S,Markowitz SD,Chan AT

更新日期：2014-04-23 00:00:00

abstract：:Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detail...

journal_title：Science translational medicine

authors： Cho RJ,Alexandrov LB,den Breems NY,Atanasova VS,Farshchian M,Purdom E,Nguyen TN,Coarfa C,Rajapakshe K,Prisco M,Sahu J,Tassone P,Greenawalt EJ,Collisson EA,Wu W,Yao H,Su X,Guttmann-Gruber C,Hofbauer JP,Hashmi R,Fue

更新日期：2018-08-22 00:00:00

abstract：:Vaccines against influenza viruses with pandemic potential, including H5N1, are under development. Because of a lack of preexisting immunity to these viruses, adjuvants (immune potentiators or enhancers) are needed to improve immune responses, to conserve scarce vaccine, and for cross-protection against strains that h...

journal_title：Science translational medicine

authors： Khurana S,Chearwae W,Castellino F,Manischewitz J,King LR,Honorkiewicz A,Rock MT,Edwards KM,Del Giudice G,Rappuoli R,Golding H

更新日期：2010-01-20 00:00:00

abstract：:Paving the way for clinical trials, a new study shows that a glutamate receptor antagonist reduces repetitive behavior and social deficits in a mouse model of autism spectrum disorder. ...

journal_title：Science translational medicine

authors： Gomez-Mancilla B

更新日期：2012-04-25 00:00:00

abstract：:Currently, no vaccine exists for hepatitis C virus (HCV), a major pathogen thought to infect 170 million people globally. Many studies suggest that host T cell responses are critical for spontaneous resolution of disease, and preclinical studies have indicated a requirement for T cells in protection against challenge....

journal_title：Science translational medicine

authors： Barnes E,Folgori A,Capone S,Swadling L,Aston S,Kurioka A,Meyer J,Huddart R,Smith K,Townsend R,Brown A,Antrobus R,Ammendola V,Naddeo M,O'Hara G,Willberg C,Harrison A,Grazioli F,Esposito ML,Siani L,Traboni C,Oo Y

更新日期：2012-01-04 00:00:00

abstract：:About 170 million people worldwide are infected with hepatitis C virus (HCV). The current standard therapy leads to sustained viral elimination in only approximately 50% of the treated patients. Telaprevir, an HCV protease inhibitor, has substantial antiviral activity in patients with chronic HCV infection. However, i...

journal_title：Science translational medicine

authors： Rong L,Dahari H,Ribeiro RM,Perelson AS

更新日期：2010-05-05 00:00:00