ライフサイエンスコーパス: hemophilia

1 anti-C1 antibodies present in patients with hemophilia.

2 sodes in patients with inhibitor-complicated hemophilia.

3 less severe bleeding when co-inherited with hemophilia.

4 mutation is the most common mutation type in hemophilia.

5 therefore be effective for the treatment of hemophilia.

6 esents an important goal in the treatment of hemophilia.

7 from deficiencies in factors VIIIa or IXa in hemophilia.

8 physicians are directed towards people with hemophilia.

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

10 eeding risk, guiding the current practice in hemophilia.

11 formation over protection from blood loss in hemophilia.

12 r severely compromises hemostasis and causes hemophilia.

13 ssue-specific expression in gene therapy for hemophilia.

14 nt of TFPI-blocking pharmaceuticals to treat hemophilia.

15 ional analysis to primate models of acquired hemophilia.

16 ributes to the hemostatic effect of FVIIa in hemophilia.

17 ffers superior therapeutic opportunities for hemophilia.

18 ma (PRP) from patients with mild or moderate hemophilia.

19 125 000, of whom 418 000 should have severe hemophilia.

20 on without long-term toxicity in adults with hemophilia.

21 a novel approach for future clinical care in hemophilia.

22 There is a rationale for studying EPCR in hemophilia.

23 o control joint bleeding in animal models of hemophilia.

24 developed and tested our pipeline using the hemophilia A & B MIP design from the "My Life, Our Futur

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

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

27 Acquired hemophilia A (AHA) is due to autoantibodies against coag

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

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

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

31 ated men (18 to 65 years of age) with severe hemophilia A (factor VIII activity, <1%) to receive a si

32 Near-to-complete correction of hemophilia A (factor VIII deficiency) and hemophilia B (

33 nd biologic results in 15 adults with severe hemophilia A (factor VIII level, <=1 IU per deciliter) w

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

35 For this, we first generated hemophilia A (FVIII-/-) mice lacking EPCR (EPCR-/-FVIII-

36 Hemophilia A (HA) and hemophilia B (HB) are the most com

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

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

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

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

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

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

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

44 endogenous factor VIII (FVIII) expression in hemophilia A (HA).

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

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

47 tuting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb

48 At variance with hemophilia A and B and von Willebrand disease, RCDs are

49 Hemophilia A and B are inherited bleeding disorders char

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

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

52 Hemophilia A and B, diseases caused by the lack of facto

53 ed bleeding disorders, including carriers of hemophilia A and B, or with von Willebrand disease, have

54 d treatment of the prevalent bone defects in hemophilia A and B.

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

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

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

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

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

60 Treatment goals in severe hemophilia A are expanding beyond low annualized bleed r

61 These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns af

62 tly change the treatment paradigm for severe hemophilia A by providing optimal protection against all

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

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

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

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

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

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

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

70 in general and have implication for ongoing hemophilia A gene-therapy clinical trials.

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

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

73 od from F8-/-/PN-1-/- and from patients with hemophilia A incubated with a PN-1-neutralizing antibody

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

75 Hemophilia A is a bleeding disorder caused by a deficien

76 Hemophilia A is a monogenic disease with a blood clottin

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

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

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

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

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

82 2bF8) gene therapy can improve hemostasis in hemophilia A mice, even in the presence of inhibitory an

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

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

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

86 Ferriere et al present an emicizumab-adapted hemophilia A mouse bleeding model that can help answer t

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

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

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

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

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

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

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

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

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

96 responses, including inhibitor responses in hemophilia A patients.

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

98 erties show high interpatient variability in hemophilia A patients.

99 I PK profile in a population of 43 pediatric hemophilia A patients.

100 O variants that modify FVIII PK in pediatric hemophilia A patients.

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

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

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

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

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

106 h AAV5-hFVIII-SQ vector in participants with hemophilia A resulted in sustained, clinically relevant

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

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

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

110 minates how inhibitory antibodies complicate hemophilia A therapy.

111 antibody emicizumab is increasingly used for hemophilia A treatment.

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

113 Nine dogs with hemophilia A were treated with adeno-associated viral (A

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

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

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

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

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

119 ries is 30% for hemophilia A, 37% for severe hemophilia A, 24% for hemophilia B, and 27% for severe h

120 rities of hemophilia A, 6.0 cases for severe hemophilia A, 3.8 cases for all severities of hemophilia

121 vantage for high-income countries is 30% for hemophilia A, 37% for severe hemophilia A, 24% for hemop

122 rities of hemophilia A, 9.5 cases for severe hemophilia A, 5.0 cases for all severities of hemophilia

123 0 males) is 17.1 cases for all severities of hemophilia A, 6.0 cases for severe hemophilia A, 3.8 cas

124 0 males) is 24.6 cases for all severities of hemophilia A, 9.5 cases for severe hemophilia A, 5.0 cas

125 Hemophilia A, a bleeding disorder resulting from F8 muta

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

127 early-phase study involving men with severe hemophilia A, a single intravenous injection of BIVV001

128 Hemophilia A, an X-linked bleeding disorder caused by de

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

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

131 ucts have improved the care of patients with hemophilia A, but the short half-life of these products

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

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

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

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

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

137 non-FVIII alternative to reduce bleeding in hemophilia A, the question of how much clotting is enoug

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

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

140 pment of liver-directed AAV gene therapy for hemophilia A, while emphasizing the importance of long-t

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

142 outcomes with gene therapy in patients with hemophilia A.

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

144 lating this strategy to clinical therapy for hemophilia A.

145 sent in inhibitor plasmas from patients with hemophilia A.

146 cement products enable comprehensive care in hemophilia A.

147 of previously untreated patients with severe hemophilia A.

148 is clotting factor to treat individuals with hemophilia A.

149 FVIII inhibitors, and patients with acquired hemophilia A.

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

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

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

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

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

155 mice of 2 different strain backgrounds with hemophilia A.

156 pic variability is well recognized in severe hemophilia A.

157 lso arise spontaneously in cases of acquired hemophilia A.

158 variability found among patients with severe hemophilia A.

159 ng previously untreated patients with severe hemophilia A.

160 ion as a therapeutic option for persons with hemophilia A.

161 ng-term and safe treatment for patients with hemophilia A.

162 and could represent a curative treatment for hemophilia A.

163 issense mutations lead to moderate to severe hemophilia A.

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

165 VIII alloantibody formation in patients with hemophilia A.

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

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

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

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

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

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

172 ivery vector for several diseases, including hemophilia and Huntington's disease, and has a demonstra

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

174 e on advances in clinical gene therapies for hemophilia and its continued development.

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

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

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

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

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

180 Prevalence of hemophilia as a proportion of cases to the male populati

181 cases to the male population, prevalence of hemophilia at birth as a proportion of cases to live mal

182 , circulate in the majority of patients with hemophilia B (CRM(+)).

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

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

185 of hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) have now been achiev

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

187 Hemophilia A (HA) and hemophilia B (HB) are the most common severe bleeding di

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

189 Hemophilia B (HB) is a life-threatening inherited diseas

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

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

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

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

194 The results in this mouse model of CRM(+) hemophilia B demonstrate that the endogenous expression

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

196 l (cross-reactive material negative, CRM(-)) hemophilia B mice suggest the concentration of Col4 read

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

198 In bleeding CRM(-) hemophilia B mice, the times to first clot at a saphenou

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

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

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

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

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

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

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

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

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

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

209 emophilia A, 3.8 cases for all severities of hemophilia B, and 1.1 cases for severe hemophilia B.

210 emophilia A, 5.0 cases for all severities of hemophilia B, and 1.5 cases for severe hemophilia B.

211 ilia A, 37% for severe hemophilia A, 24% for hemophilia B, and 27% for severe hemophilia B.

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

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

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

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

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

217 In hemophilia B, this FIX-Col4 interaction reduces the plas

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

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

220 uccess, particularly in patients with severe hemophilia B.

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

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

223 IXa variants that are associated with severe hemophilia B.

224 A, 24% for hemophilia B, and 27% for severe hemophilia B.

225 es of hemophilia B, and 1.1 cases for severe hemophilia B.

226 es of hemophilia B, and 1.5 cases for severe hemophilia B.

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

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

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

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

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

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

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

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

235 valuated fibrosis markers in the Multicenter Hemophilia Cohort Studies (MHCS), which included subject

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

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

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

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

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

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

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

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

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

245 The Hemophilia Inhibitor Genetics Study (HIGS) Combined Coho

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

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

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

249 Hemophilia is a bleeding disorder caused by deficiency i

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

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

252 The prevalence of hemophilia is higher than previously estimated.

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

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

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

256 es the hemostatic effect of FVIIa in a mouse hemophilia model, when assayed as ferric chloride-induce

257 Inhibition of TFPI enhances coagulation in hemophilia models.

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

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

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

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

262 joint damage is the primary co-morbidity of hemophilia, osteoporosis and osteopenia are also observe

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

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

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

266 In hemophilia patients without inhibitors, the initiation o

267 thus bears potential to prevent bleeding in hemophilia patients.

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

269 active new target to prevent joint damage in hemophilia patients.

270 nslates into normalization of coagulation of hemophilia plasmas.

271 n contrast, in PRP from patients with severe hemophilia, PN-1 neutralization did not improve thrombin

272 The large observed variability in hemophilia prevalence prevents robust estimation of burd

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

274 The participants with hemophilia received three injections of fitusiran admini

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

276 Patients with hemophilia still have a life expectancy disadvantage.

277 velopment of novel hemostatic approaches for hemophilia, such as the use of nonsubstitutive therapy a

278 Nonetheless, studies in animal models of hemophilia suggest that the approach can also be used fo

279 therapies for the X-linked bleeding disorder hemophilia that are currently in clinical development, g

280 In contrast to congenital hemophilia, the patient's residual FVIII activity does n

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

282 ytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal ant

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

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 New therapeutic strategies for hemophilia treatment that do not rely on clotting factor

291 sidered the most significant complication of hemophilia treatment.

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

293 e the bone healing following hemarthrosis in hemophilia we examined a two week time course using micr

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 The expected number of patients with hemophilia worldwide is 1 125 000, of whom 418 000 shoul