更新于：2024-11-01

Allan-Herndon-Dudley Syndrome

Allan-Herndon-Dudley综合征

更新于：2024-11-01

基本信息

别名

AHDS、ALLAN-HERNDON SYNDROME、ALLAN-HERNDON-DUDLEY SYNDROME

+ [26]

简介

A rare, X-linked recessive inherited syndrome caused by mutations in the SLC16A2 (MCT8) gene. It affects exclusively males and is characterized by mental retardation, limited mobility, muscle hypoplasia, hypotonia, contractures, and spasticity.

关联

项与 Allan-Herndon-Dudley综合征相关的药物

Tiratricol

替拉曲可

靶点

THR-α x THR-β

作用机制

THR-α激动剂 [+1]

在研机构

Rare Thyroid Therapeutics International AB [+1]

原研机构-

在研适应症

Allan-Herndon-Dudley综合征

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区-

首次获批日期1800-01-20

SRW101

靶点

THR

作用机制

THR调节剂

在研机构

PriZm, LLC

原研机构-

在研适应症

Allan-Herndon-Dudley综合征

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

Diiodothyropropionic Acid

靶点

THR

作用机制

THR激动剂

在研机构-

原研机构

Zarin Pharmaceuticals Ltd

在研适应症-

非在研适应症

Allan-Herndon-Dudley综合征 [+1]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与 Allan-Herndon-Dudley综合征相关的临床试验

CTIS2024-516124-34-00 / Recruiting

Withdrawal of Tiratricol Treatment in Males with Monocarboxylate Transporter 8 Deficiency (MCT8 Deficiency): A Doubleblind, Randomized, Placebocontrolled Study (MCT8-2021-3 (ReTRIACt)) - MCT8-2021-3

开始日期2023-07-21

申办/合作机构

Rare Thyroid Therapeutics International AB

NCT05579327 / Recruiting临床3期

Withdrawal of Tiratricol Treatment in Males with Monocarboxylate Transporter 8 Deficiency (MCT8 Deficiency): a Double-blind, Randomized, Placebo-controlled Study

This is a double-blind, randomized phase 3 multicenter placebo-controlled study in at least 16 evaluable male participants diagnosed with MCT8 deficiency. Male participants, from 4 years of age (at randomization) and having demonstrated stable maintenance treatment with tiratricol, will be randomized to receive placebo or tiratricol for 30 days or until reaching rescue criterion (serum total triiodothyronine [T3] > upper limit of normal [ULN] of the participant's normal range, for a sample collected during the 30-day Randomized Treatment Period). The research hypothesis to be tested is that, for participants in the placebo group, removal of tiratricol will lead to an increase of serum total T3 concentration, measured by liquid chromatography with tandem mass spectrometry (LC/MS/MS), above the ULN and requirement of rescue treatment with tiratricol, compared to those who continue to receive tiratricol.

开始日期2023-07-21

申办/合作机构

Rare Thyroid Therapeutics International AB

[+2]

ISRCTN98332431 / Completed临床1期

Bioequivalence of two tiratricol tablets and relative bioavailability of tiratricol in the fasted and fed state in healthy male subjects combined with an assessment of dose-proportionality: a randomised, five-period crossover study

开始日期2023-07-06

申办/合作机构

Rare Thyroid Therapeutics International AB

100 项与 Allan-Herndon-Dudley综合征相关的临床结果

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100 项与 Allan-Herndon-Dudley综合征相关的转化医学

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0 项与 Allan-Herndon-Dudley综合征相关的专利（医药）

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425

项与 Allan-Herndon-Dudley综合征相关的文献（医药）

2024-11-01·Annals of Surgical Oncology

Clinical Implications of the Degree of Pancreatic Invasion in Ampulla of Vater Carcinoma

Article

作者: Ashida, Ryo ; Sugiura, Teiichi ; Otsuka, Shimpei ; Ohgi, Katsuhisa ; Yamada, Mihoko ; Kato, Yoshiyasu ; Norose, Tomoko ; Sugino, Takashi ; Uesaka, Katsuhiko ; Ohike, Nobuyuki ; Miura, Yuya

BACKGROUNDAmpulla of Vater carcinoma (AVC) stage T3 was subdivided according to the degree of pancreatic invasion into T3a (≤ 0.5 cm) and T3b (> 0.5 cm) by the 8th edition of the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) cancer staging system. However, the differences in clinicopathological features and survival outcomes between the two categories have not been well discussed.PATIENTS AND METHODSWe retrospectively analyzed 133 consecutive patients who underwent pancreatoduodenectomy for AVC at our institution between 2002 and 2020. Clinicopathological features and survival outcomes of patients with AVC were analyzed, with a focus on the depth of pancreatic invasion. In addition, the survival outcomes of patients with T3 AVC were compared with those of patients with resectable pancreatic head carcinoma (R-PhC) who underwent pancreatoduodenectomy during the same period.RESULTSThe overall survival (OS) in patients with T3b AVC (n = 12) was significantly worse than that in patients with T3a AVC (n = 39) [median survival time (MST) 9.2 vs. 74.5 months, p < 0.001). A multivariate analysis identified T3b tumor (hazard ratio 5.64, p = 0.009) as an independent prognostic factor. The OS of patients with T3a AVC was significantly better than that of patients with R-PhC who received adjuvant chemotherapy (n = 276, MST 35.0 months, p = 0.007). In contrast, the OS of patients with T3b AVC tended to be worse than that of patients with R-PhC managed without adjuvant chemotherapy, although this difference was not statistically significant (n = 163; MST, 17.5; p = 0.140).CONCLUSIONSAVC with > 0.5 cm invasion into the pancreas was associated with poor survival and represented advanced tumor progression to systemic disease.

2024-10-01·Neurobiology of Disease

Defective thyroid hormone transport to the brain leads to astroglial alterations

Article

作者: Bárez-López, Soledad ; Guillén-Yunta, Marina ; Matheus, Maria Gisele ; Sanz-Bógalo, Ainara ; Valcárcel-Hernández, Víctor ; Guadaño-Ferraz, Ana ; Muñoz-Moreno, Emma ; García-Aldea, Ángel ; Montero-Pedrazuela, Ana ; Grijota-Martínez, Carmen

Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked disorder that causes severe neurological damage, for which there is no effective treatment. AHDS is due to inactivating mutations in the thyroid hormone transporter MCT8 that impair the entry of thyroid hormones into the brain, resulting in cerebral hypothyroidism. However, the pathophysiology of AHDS is still not fully understood and this is essential to develop therapeutic strategies. Based on evidence suggesting that thyroid hormone deficit leads to alterations in astroglial cells, including gliosis, in this work, we have evaluated astroglial impairments in MCT8 deficiency by means of magnetic resonance imaging, histological, ultrastructural, and immunohistochemical techniques, and by mining available RNA sequencing outputs. Apparent diffusion coefficient (ADC) imaging values obtained from magnetic resonance imaging showed changes indicative of alterations in brain cytoarchitecture in MCT8-deficient patients (n = 11) compared to control subjects (n = 11). Astroglial alterations were confirmed by immunohistochemistry against astroglial markers in autopsy brain samples of an 11-year-old and a 30th gestational week MCT8-deficient subjects in comparison to brain samples from control subjects at similar ages. These findings were validated and further explored in a mouse model of AHDS. Our findings confirm changes in all the astroglial populations of the cerebral cortex in MCT8 deficiency that impact astrocytic metabolic and mitochondrial cellular respiration functions. These impairments arise early in brain development and persist at adult stages, revealing an abnormal distribution, density, morphology of cortical astrocytes, along with altered transcriptome, compatible with an astrogliosis-like phenotype at adult stages. We conclude that astrocytes are potential novel therapeutic targets in AHDS, and we propose ADC imaging as a tool to monitor the progression of neurological impairments and potential effects of treatments in MCT8 deficiency.

2024-09-19·Cancer research and treatment

Stage Evaluation of Cystic Duct Cancer.

Article

作者: Hwang, Shin ; Lee, Woohyung ; Cho, HyungJun ; Yoo, Daegwang ; Sung, You-Na ; Lee, Kyung Jin ; Jun, Sun-Young ; Kim, Yeseul ; Jung, Haesung ; Hong, Seung-Mo

PurposeCystic duct cancers (CDCs) have been classified as extrahepatic bile duct cancers or gallbladder cancers (GBCs); however, it is unclear whether their clinical behavior is similar to that of distal extrahepatic bile duct cancers (DBDCs) or GBCs.Materials and MethodsT category of the CDCs was classified using current T category scheme of the GBCs and DBDCs, and clinicopathological factors were compared among 38 CDCs, 345 GBCs, and 349 DBDCs. We modified Nakata's classifications (type 1, confined within cystic duct (CD); combined types 2-4, extension beyond CD) and compared them.ResultsNo significant overall survival (OS) difference was observed between the patients with CDC, GBC, and DBDC. The T category of GBC staging was more accurate at distinguishing OS in patients with CDC than the DBDC staging. Patients with T3 CDC and GBC showed a significant OS difference when using the T category for GBC staging, while those with T1-T2 CDC and GBC showed no significant difference. In contrast, the T category of DBDC staging did not show any significant OS difference between patients with T1-T2 CDC and DBDC or T3 CDC and DBDC. Patients with type 1 CDC had significantly better OS than those with combined types.ConclusionUnlike GBCs and DBDCs, CDCs exhibit distinct clinicopathological characteristics. The OS is better when the CDC confines within the CD, compared to when it extends beyond it. Therefore, we propose a new T category scheme (T1, confined to CD; T2, invaded beyond CD) for better classifying CDCs.

项与 Allan-Herndon-Dudley综合征相关的新闻（医药）

2023-03-31

·FierceBiotech

What M&A slowdown? Buyers circle GreenLight Biosciences, Egetis Therapeutics

Both GreenLight and Egetis pointed out that they hadn't accepted an offer yet. While biotech M&A may have cooled down over the past year, no one has told GreenLight Biosciences or Egetis Therapeutics, which are both mulling takeover offers. RNA-focused GreenLight announced yesterday that it has received an offer from VC firm Fall Line Capital’s Fall Line Endurance Fund to acquire all outstanding stock of the biotech for 60 cents per share. GreenLight— which spreads itself across vaccines and therapies for humans as well as agricultural solutions—only went public via a special purpose acquisition company (SPAC) merger in February 2022. The merger agreement valued the company at $1.2 billion and GreenLight’s stock hit a high of over $12 per share in the following weeks. But it’s been dropping ever since, with a closing price Thursday of just 43 cents. Still, the biotech emphasized that no sale has been agreed yet, with the company’s board of directors due to “carefully evaluate Fall Line’s indication of interest within the context of the ongoing review of various alternatives and in consultation with any financial and legal advisors it may retain.” GreenLight ended 2022 with $68.1 million in cash and equivalents. Despite pausing its gene therapy program for sickle cell anemia and cutting 25% of staff in October 2022 to save money, the company still expects reserves to run dry by June. The biotech had already announced it was looking at a range of measures to eke out its runway, including “further management of program spending, additional platform licensing collaborations and potential further financing activities.” Even with human health ambitions now limited to preclinical vaccine candidates for pan-sarbecovirus and shingles, as well as a cancer vaccine collab with EpiVax, it’s not surprising the company is open to external offers. Less is known about Egetis’ offer. The biotech released a concise note yesterday responding to “existing rumors” by confirming that the company “has ongoing discussions with certain external parties regarding a potential acquisition.” Again, Egetis was keen to stress that no offer has yet been agreed. The Swedish company’s lead product is Emcitate, which is in phase 2 trials for Allan-Herndon-Dudley syndrome, a rare genetic disorder that impacts a child's cognition, mobility and overall health and for which there is currently no available treatment. Egetis plans to submit a request for EU approval in the second quarter of the year based on existing clinical data.