ライフサイエンスコーパス: hemophilia

1 o control joint bleeding in animal models of hemophilia.

2 bin (AT) as a means to promote hemostasis in hemophilia.

3 anti-C1 antibodies present in patients with hemophilia.

4 formation over protection from blood loss in hemophilia.

5 sodes in patients with inhibitor-complicated hemophilia.

6 ssue-specific expression in gene therapy for hemophilia.

7 nt of TFPI-blocking pharmaceuticals to treat hemophilia.

8 less severe bleeding when co-inherited with hemophilia.

9 d in the general population of patients with hemophilia.

10 ith adeno-associated viral (AAV) vectors for hemophilia.

11 imary physiological regulator of bleeding in hemophilia.

12 1 may constitute a novel treatment option in hemophilia.

13 mutation is the most common mutation type in hemophilia.

14 mutations or in autoimmune-mediated acquired hemophilia.

15 TFPI deficiency on bleeding and clotting in hemophilia.

16 therefore be effective for the treatment of hemophilia.

17 esents an important goal in the treatment of hemophilia.

18 physicians are directed towards people with hemophilia.

19 velopment of successful gene therapy for the hemophilias.

20 odies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are

21 Acquired hemophilia A (AHA) is an autoimmune disease caused by an

22 Acquired hemophilia A (AHA) is caused by autoantibodies against f

23 FVIII inhibitors, are the cause of acquired hemophilia A (AHA).

24 cipants were >/=12 years of age, with severe hemophilia A (endogenous FVIII <1%).

25 icles can be adapted to hemophilic patients (hemophilia A (F-VIII deficient) and hemophilia B (F-IX d

26 bitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL).

27 aluated 574 consecutive patients with severe hemophilia A (factor VIII activity, <0.01 IU per millili

28 The risk for inhibitor development in mild hemophilia A (factor VIII levels between 5 and 40 U/dL)

29 h acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C

30 I (hFVIII) were systematically evaluated for hemophilia A (HA) gene therapy.

31 Injection of FVIII-RH protein in hemophilia A (HA) mice resulted in more efficacious hemo

32 In the naive FVIII null hemophilia A (HA) mouse, platelet-derived VIII prevents

33 African American hemophilia A (HA) patients experience a higher incidence

34 factor VIII (FVIII) inhibitors seen in black hemophilia A (HA) patients is not due to a mismatch betw

35 e, elicits unwanted anti-FVIII antibodies in hemophilia A (HA) patients.

36 stematic analysis of missense mutations from hemophilia A (HA) patients.

37 iously untreated patients (PUPs) with severe hemophilia A (HA).

38 e seen in 25% to 30% of patients with severe hemophilia A (HA).

39 dies ("inhibitors") are a serious problem in hemophilia A (HA).

40 tabases detailing >2100 unique mutations for hemophilia A and >1100 mutations for hemophilia B, these

41 Hemophilia A and B are inherited bleeding disorders char

42 and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels.

43 Treatment of patients with hemophilia A and B has undergone significant advances du

44 mmonest severe inherited bleeding disorders, hemophilia A and B.

45 has shown great promise for the treatment of hemophilia A and B.

46 nt of inhibitory antibodies in patients with hemophilia A and discuss how these findings may be inter

47 e tool, particularly in patients with severe hemophilia A and good risk profiles, and leads to a retu

48 New therapies for hemophilia A and hemophilia B will likely continue to ch

49 found in different cohorts of patients with hemophilia A and in healthy individuals.

50 II) antibodies that develop in patients with hemophilia A and in murine hemophilia A models, clinical

51 acious prevention and treatment of bleeds in hemophilia A at reduced dosing frequency.

52 Conversely, individuals with hemophilia A caused by F8 missense mutations are CRM-pos

53 Most inhibitor patients with hemophilia A develop antibodies against the fVIII A2 and

54 Approximately 30% of patients with severe hemophilia A develop inhibitory anti-factor VIII (fVIII)

55 BOECs isolated from hemophilia A dogs transduced with this lentiviral vector

56 All 3 hemophilia A dogs treated with FVIII-expressing autologo

57 implanted into the omentum of 2 normal and 3 hemophilia A dogs.

58 Individuals with hemophilia A due to major deletions of the FVIII gene (F

59 ; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected

60 factor VIII (FVIII) is used in patients with hemophilia A for treatment of bleeding episodes or for p

61 ng without toxicity and translate success to hemophilia A gene therapy.

62 ed and novel approaches for the treatment of hemophilia A has expanded tremendously.

63 vel recombinant FVIII (rFVIII) therapies for hemophilia A have been in clinical development, which ai

64 e very early phenotypic expression of severe hemophilia A in 621 consecutively enrolled, well-charact

65 inhibitory Abs to factor VIII in people with hemophilia A indicate a complex process involving multip

66 y in previously treated subjects with severe hemophilia A investigated safety and pharmacokinetics of

67 Hemophilia A is a bleeding disorder caused by a deficien

68 with severe cases of congenital or acquired hemophilia A is the development of inhibitor antibodies

69 Inhibitor formation in hemophilia A is the most feared treatment-related compli

70 Hemophilia A is the X-linked bleeding disorder caused by

71 ibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for repl

72 blood outgrowth endothelial cells (BOECs) to hemophilia A mice and showed that these cells remained s

73 responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized

74 2bF8) gene therapy can improve hemostasis in hemophilia A mice, even in the presence of inhibitory an

75 MAbs were injected into hemophilia A mice, followed by injection of human B doma

76 acute and prolonged vascular injury model in hemophilia A mice.

77 2 monoclonal Abs (mAbs) produced in a murine hemophilia A model.

78 in patients with hemophilia A and in murine hemophilia A models, clinically termed "inhibitors," bin

79 ease fVIII clearance and are pathogenic in a hemophilia A mouse tail snip bleeding model.

80 and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibo

81 sed thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibo

82 in phase 1 clinical testing in subjects with hemophilia A or B.

83 potency of ADHLSCs to control bleeding in a hemophilia A patient and assess the biodistribution of t

84 I-binding antibodies in different cohorts of hemophilia A patients and in healthy individuals.

85 This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Aust

86 ompetence and inhibitor status by evaluating hemophilia A patients harboring F8-null mutations that w

87 ve and 174 inhibitor-negative Italian severe hemophilia A patients using a TaqMan genotyping assay.

88 creased incidence of anti-drug antibodies in hemophilia A patients with haplotypes H3 and H4.

89 approach for future tolerogenic treatment of hemophilia A patients with inhibitors.

90 A major problem in treating hemophilia A patients with therapeutic factor VIII (FVII

91 o FVIII is a serious problem in treatment of hemophilia A patients, we investigated the potential of

92 specific IgG to FVIII half-life reduction in hemophilia A patients.

93 responses, including inhibitor responses in hemophilia A patients.

94 anti-FVIII inhibitory antibody formation in hemophilia A patients.

95 r complication in the replacement therapy of hemophilia A patients.

96 ctor VIII replacement therapy for congenital hemophilia A patients.

97 bin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which p

98 velopment was investigated in all 407 severe hemophilia A previously untreated patients born in the U

99 Among 235 randomized patients with severe hemophilia A previously untreated with FVIII concentrate

100 Patients with hemophilia A rely on exogenous factor VIII to prevent bl

101 ver, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the ra

102 recombinant T-cell receptor obtained from a hemophilia A subject's T-cell clone, into expanded human

103 binant T-cell receptor (TCR) isolated from a hemophilia A subject's T-cell clone.

104 115 "good-risk," severe high-titer inhibitor hemophilia A subjects.

105 man use of a new nonsubstitutive therapy for hemophilia A that can potentially be disruptive to the w

106 minates how inhibitory antibodies complicate hemophilia A therapy.

107 A patient suffering from hemophilia A was injected with repeated doses of ADHLSCs

108 ciation study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with hum

109 e of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII co

110 ealthy individuals, patients with congenital hemophilia A with and without FVIII inhibitors, and pati

111 roved thrombin generation in an NHP model of hemophilia A with anti-factor VIII inhibitors.

112 f 42 adult patients with severe and moderate hemophilia A without inhibitors.

113 approximately 50% of individuals with severe hemophilia A) have been grouped with the former on the b

114 Defects or deficiency of FVIII cause Hemophilia A, a mild to severe bleeding disorder.

115 ity criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor

116 on of AT levels in wild-type mice, mice with hemophilia A, and nonhuman primates (NHPs).

117 eotide repeat expansions in diseases such as hemophilia A, fragile X syndrome, Hunter syndrome, and F

118 ts with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease.

119 in previously untreated patients with severe hemophilia A, high-dosed intensive FVIII treatment incre

120 or previously untreated children with severe hemophilia A, it is unclear whether the type of factor V

121 therapy can be lifesaving for patients with hemophilia A, neutralizing alloantibodies to FVIII, know

122 VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding patter

123 In a mouse model of hemophilia A, the complex normalized hemostasis upon vas

124 In hemophilia A, the most severe complication of factor VII

125 nhibitor development in patients with severe hemophilia A, we applied whole-exome sequencing (WES) an

126 g this strategy into the canine (c) model of hemophilia A, we increased cFVIII transgene expression b

127 and could represent a curative treatment for hemophilia A.

128 of previously untreated patients with severe hemophilia A.

129 VIII alloantibody formation in patients with hemophilia A.

130 III (AAV5-hFVIII-SQ) in nine men with severe hemophilia A.

131 is clotting factor to treat individuals with hemophilia A.

132 FVIII inhibitors, and patients with acquired hemophilia A.

133 s is the basis of modern treatment of severe hemophilia A.

134 (LV)-mediated human platelet gene therapy of hemophilia A.

135 y treated males aged >/=12 years with severe hemophilia A.

136 elet-derived FVIII can improve hemostasis in hemophilia A.

137 obulin G1 (IgG1) in 165 patients with severe hemophilia A.

138 mice of 2 different strain backgrounds with hemophilia A.

139 pic variability is well recognized in severe hemophilia A.

140 lso arise spontaneously in cases of acquired hemophilia A.

141 variability found among patients with severe hemophilia A.

142 ng previously untreated patients with severe hemophilia A.

143 the life-span among participants with severe hemophilia A.

144 nt impediment to the effective management of hemophilia A.

145 required to prevent bleeding associated with hemophilia A.

146 the importance of F8 genotyping in nonsevere hemophilia A.

147 ombinant) impair the effective management of hemophilia A.

148 outcomes with gene therapy in patients with hemophilia A.

149 152 patients (1-65 years of age) with severe hemophilia A.

150 he immune response to FVIII in patients with hemophilia A.

151 issense mutations lead to moderate to severe hemophilia A.

152 potential use of ADHLSCs in the treatment of hemophilia A.

153 es (inhibitors) is the major complication in hemophilia A.

154 lating this strategy to clinical therapy for hemophilia A.

155 sent in inhibitor plasmas from patients with hemophilia A.

156 tion and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled a

157 h sickle cell disease, beta-thalassemia, and hemophilia A/B or von Willebrand disease, respectively.

158 different categories of patients with severe hemophilia A: previously untreated patients, multiply tr

159 untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe

160 I], 1.14-5.20), sex between men and women or hemophilia (aHR, 3.43; 95% CI, 1.70-6.93), and sex betwe

161 rogress of AAV-mediated gene therapy for the hemophilias, along with its upcoming prospects and chall

162 ly effective in populations of patients with hemophilia and inhibitors; however, individuals may show

163 in regard to demographics, complications of hemophilia and its treatment, and mortality.

164 N-AT3 promoted hemostasis in mouse models of hemophilia and led to improved thrombin generation in an

165 nsity is a growing concern in aging men with hemophilia and may result in high-morbidity fragility fr

166 ent thrombin generation is the root cause of hemophilia, and excessive thrombin production results in

167 ing of men who have sex with men, males with hemophilia, and injection drug users (IDUs) (n = 1865).

168 cluding Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy.

169 infections, malignant hematologic disorders, hemophilia, and the hemoglobin disorders.

170 ovements in quality of life for persons with hemophilia, are in late-phase clinical development.

171 were 12 years of age or older and had severe hemophilia B (endogenous factor IX level of </=2 IU per

172 atients (hemophilia A (F-VIII deficient) and hemophilia B (F-IX deficient)) with a risk of bleeding,

173 al, open-label study included 10 adults with hemophilia B (FIX </=2% of normal) and severe-bleeding p

174 ced immune tolerance to factor IX (FIX) in a hemophilia B (HB) dog with previously formed anti-FIX in

175 sense mutations, present in 70% (324/469) of hemophilia B (HB) patients with PTCs.

176 sing adeno-associated viral (AAV) vector for hemophilia B (HB) showed that the risk of cellular immun

177 Studies on gene therapy for hemophilia B (HB) using adeno-associated viral (AAV) vec

178 als, most notably for those in patients with hemophilia B (ref.

179 Gene therapy for hemophilia B aims to ameliorate bleeding risk and provid

180 s and limitations of this clinical trial for hemophilia B and approaches to advance beyond this miles

181 al in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of

182 hylactic factor replacement in patients with hemophilia B improves outcomes but requires frequent inj

183 hilia and used it to improve gene therapy of hemophilia B in dogs, and Cantore et al have shown simil

184 Fc (Alprolix) and wild-type FIX (BeneFIX) in hemophilia B mice 7 days postinfusion.

185 In summary, 7 days postinfusion into hemophilia B mice, BeneFIX and Alprolix are hemostatical

186 n (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice.

187 with FVIIa (EGF2 and catalytic domain) into hemophilia B mice.

188 ociated virus serotype 9 (scAAV9) vectors in hemophilia B mice.

189 ve as mouse FVIIa in controlling bleeding in hemophilia B mice.

190 ition in an intravital laser injury model in hemophilia B mice.

191 xtending this success to a greater number of hemophilia B patients remains a major goal of the field,

192 ion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in ci

193 y process recombinant factor IX (rFIX) limit hemophilia B therapy to <20% of the world's population.

194 demonstrated successful conversion of severe hemophilia B to mild or moderate disease in 6 adult male

195 in (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing.

196 s per kilogram of body weight in 10 men with hemophilia B who had factor IX coagulant activity of 2%

197 New therapies for hemophilia A and hemophilia B will likely continue to change clinical pra

198 ted bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease.

199 In patients with severe hemophilia B, gene therapy that is mediated by a novel s

200 In a trial for hemophilia B, long-term expression of human FIX has been

201 patients who fail to respond to ITI or have hemophilia B, new and improved tools are needed.

202 In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vect

203 transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding r

204 ons for hemophilia A and >1100 mutations for hemophilia B, these diseases are among the most extensiv

205 inical trials including gene replacement for Hemophilia B, X-linked Severe Combined Immunodeficiency,

206 t a Factor IX (FIX)-deficient mouse model of hemophilia B.

207 ector dose shown to be safe in subjects with hemophilia B.

208 w annualized bleeding rates in patients with hemophilia B.

209 vels of human factor IX in a murine model of hemophilia B.

210 2 (AAV-2)-injected muscles of a patient with hemophilia B.

211 uccess, particularly in patients with severe hemophilia B.

212 ed strategies for factor IX gene transfer in hemophilia B.

213 ucts, heralds a new era for the treatment of hemophilia B.

214 long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an ini

215 a significant challenge in the management of hemophilia because once an inhibitor is present, bleedin

216 These are exciting times for hemophilia because several new technologies that promise

217 Gene transfer studies for the treatment of hemophilia began more than two decades ago.

218 re compared also with the corresponding mild hemophilia birth cohorts (n = 2587 men total) to control

219 o recombinant proteins, possibly not only in hemophilia but also in other diseases that are treated w

220 FVIIa) is an established hemostatic agent in hemophilia, but its mechanism of action remains unclear.

221 to increase risk of bleeds in children with hemophilia, but the magnitude of the risk is unknown.

222 However, patients with severe hemophilia can mount immune responses targeting therapeu

223 e current therapy as well as new progress in hemophilia care (particularly strategies to prolong half

224 by the incremental advances and setbacks in hemophilia care in the last 50 years in the United State

225 cohorts, differentially affected by eras of hemophilia care, were examined separately in regard to d

226 ve cohort study was conducted at 3 pediatric hemophilia centers in Australia between July 2008 and Oc

227 protection from HIV-1 infection in the same hemophilia cohort, using controls from the general popul

228 oth distal radius and tibia in patients with hemophilia compared with age- and sex-matched controls.

229 Current treatment of hemophilia consists of the administration of recombinant

230 d the disability gap between severe and mild hemophilia did not narrow.

231 The boy had hemophilia due to a factor VIII autoantibody and nephrot

232 remains a substantial unmet medical need in hemophilia, especially in patients with inhibitory antib

233 ophylactic regimens for patients with severe hemophilia (factor VIII/IX < 1 IU/dL) born between 1970

234 and clot formation and have been studied in hemophilia for about 10 years.

235 including hematologic disorders such as the hemophilias, Gaucher disease, hemochromatosis, and the p

236 g, has been achieved for the first time in a hemophilia gene therapy trial.

237 e next steps to optimize the risk-benefit of hemophilia gene therapy.

238 Induction of immune tolerance to FVIII in hemophilia has been extensively studied but remains an u

239 analysis of how outcomes of men with severe hemophilia have been altered by the incremental advances

240 iseases such as Duchenne muscular dystrophy, hemophilia, heart failure, Parkinson's disease, and othe

241 ma, after major joint surgery, or as seen in hemophilia in general leads to arthropathy.

242 of novel therapeutic modalities in treating hemophilia, inflammation, cerebral malaria, and cancer.

243 The Hemophilia Inhibitor Genetics Study (HIGS) Combined Coho

244 ies were analyzed in acquired and congenital hemophilia inhibitor patients (n = 178).

245 I immune response in acquired and congenital hemophilia inhibitor patients.

246 national surveillance to monitor and inform hemophilia interventions and outcomes.

247 Hemophilia is a bleeding disorder caused by deficiency i

248 Hemophilia is a bleeding disorder that afflicts about 1

249 cardiovascular risk factors in patients with hemophilia is as prevalent as in the general population,

250 The low trabecular bone density found in hemophilia is attributed to significantly decreased trab

251 Hemophilia is caused by a functional deficiency of one o

252 t therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibit

253 ern and obstacle for research in the area of hemophilia is the relatively small cohorts available for

254 hat can potentially be disruptive to the way hemophilia is treated.

255 Prophylactic treatment in severe hemophilia is very effective but is limited by cost issu

256 ing for effective administration of FVIII to hemophilia mice to prevent bleeding.

257 Inhibition of TFPI enhances coagulation in hemophilia models.

258 pproach for inducing tolerance to FVIII in a hemophilia mouse model.

259 Here we characterize how hemophilia mutations near the unused N-glycosylation sit

260 84), in which most amino acids have multiple hemophilia mutations.

261 st uniformly examined population with severe hemophilia (n = 4899 men with severe factor VIII and IX

262 ssfully in clinical trials for patients with hemophilia or blindness, but pre-existing neutralizing a

263 has seen the progress that has been made for hemophilia over the past 40 years, from a life expectanc

264 variability in pharmacokinetic parameters in hemophilia patients A poses a challenge for optimal trea

265 zing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals.

266 markers of inhibitory antibody formation in hemophilia patients that may ultimately lead to predicti

267 ctivated factor VII is approved for treating hemophilia patients with autoantibodies to their factor

268 In hemophilia patients without inhibitors, the initiation o

269 thus bears potential to prevent bleeding in hemophilia patients.

270 ical effect of recombinant FVIIa (rFVIIa) in hemophilia patients.

271 nslates into normalization of coagulation of hemophilia plasmas.

272 decreases bleeding time and clotting time in hemophilia, possibly through inhibition of tissue factor

273 R on the action of rhFVIIa administration in hemophilia, prompting the rational design of improved an

274 Furthermore, the efficacy of fucoidan in hemophilia raises the possibility that decreased bleedin

275 The participants with hemophilia received three injections of fitusiran admini

276 Monogenic diseases, including hemophilia, represent ideal targets for genome-editing a

277 the next-generation gene therapy vectors for hemophilia requires using lower and thus potentially saf

278 s, male sex, positive HIV status, history of hemophilia, sickle cell anemia or thalassemia, history o

279 llowing vessel injury and alters bleeding in hemophilia, suggesting that its primary physiological ro

280 gest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa

281 ximately 20 years for a boy born with severe hemophilia to essentially a normal life expectancy in 20

282 architectural deficits seen in patients with hemophilia translate into significantly lower estimated

283 Factor replacement is the cornerstone of hemophilia treatment but is often not possible in develo

284 This analysis of the US Hemophilia Treatment Center Network and the Centers for

285 ely from 1998 to 2011 at federally funded US hemophilia treatment centers provided an opportunity to

286 99 and 2010 at annual clinical visits to 134 hemophilia treatment centers.

287 hus generating significant debate within the hemophilia treatment community.

288 Current hemophilia treatment involves frequent intravenous infus

289 established a prospective cohort to monitor hemophilia treatment safety.

290 sidered the most significant complication of hemophilia treatment.

291 en prevention of this severe complication of hemophilia treatment.(1)

292 ether EPCR facilitates rhFVIIa hemostasis in hemophilia using a mouse model system.

293 Disorders of hemostasis such as hemophilia, von Willebrand disease (VWD), and other clot

294 ons may ameliorate the clinical phenotype in hemophilia, we developed an RNA interference (RNAi) ther

295 ising therapeutics to treat diseases such as hemophilia which are due to endogenous protease deficien

296 On the other hand, hemophilia, which is associated with reduced thrombin ge

297 liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive rep

298 after gene transfer in 10 participants with hemophilia who received the same vector dose.

299 Patients with hemophilia, who have a lifelong hypocoagulability, seem

300 ypass FVIII as a novel treatment approach in hemophilia with and without neutralizing FVIII Abs.