更新于：2024-05-01

Niemann-Pick Disease, Type A

A型尼曼匹克病

更新于：2024-05-01

基本信息

别名

ACID SPHINGOMYELINASE DEFICIENCY, NEUROVISCERAL TYPE、ASMD, NEUROVISCERAL TYPE、A型Niemann-Pick病

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简介

The classic infantile form of Niemann-Pick Disease, caused by mutation in SPHINGOMYELIN PHOSPHODIESTERASE. It is characterized by accumulation of SPHINGOMYELINS in the cells of the MONONUCLEAR PHAGOCYTE SYSTEM and other cell throughout the body leading to cell death. Clinical signs include JAUNDICE, hepatosplenomegaly, and severe brain damage.

关联

项与 A型尼曼匹克病相关的药物

Olipudase alfa

靶点

SMPD1

作用机制

SMPD1抑制剂

在研机构

Genzyme Corp. [+2]

原研机构

Genzyme Corp.

在研适应症

酸性鞘磷脂酶缺乏症 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期2022-03-28

PLX-100

靶点-

作用机制-

在研机构

Polaryx Therapeutics, Inc.初创企业

原研机构

Polaryx Therapeutics, Inc.初创企业

在研适应症

神经元蜡样质脂褐质沉积症 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

Niemann-Pick type A disease gene therapy (Sanofi)

靶点

Sphingomyelin phosphodiesterase family

作用机制

Sphingomyelin phosphodiesterase stimulants [+1]

在研机构-

原研机构

Genzyme Corp.

在研适应症-

非在研适应症

A型尼曼匹克病

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 A型尼曼匹克病相关的临床试验

EUCTR2013-000051-40-BE / Not yet recruiting临床2期

A Long-Term Study to Assess the Ongoing Safety and Efficacy of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

开始日期2019-09-30

申办/合作机构

Genzyme Corp.

NCT04106544 / CompletedN/A

A Prospective and Retrospective Cohort Study to Refine and Expand the Knowledge on Patients With Chronic Forms of Acid Sphingomyelinase Deficiency (ASMD)

Primary Objective:
To describe the clinical features and their severity at the time of diagnosis and their evolution over time in patients with confirmed chronic visceral and chronic neurovisceral forms of ASMD
To describe Clinician-Reported Outcomes (ClinROs) and Patient-Reported Outcomes (PROs) at enrollment and their evolution over time; disease severity at the time of diagnosis and its evolution over time
Secondary Objectives:
To describe abnormal values in laboratory parameters and all values of specific clinical and imaging assessments at the time of diagnosis and their evolution over time
To study the use and applicability towards validation of a newly developed ASMD disease severity scoring system
To study the use and applicability towards validation of a newly developed ASMD PRO tool
To describe ASMD-related disease burden among patients with ASMD, caregivers, and healthcare resource utilization
To describe the association between patient demographics (eg, age, gender, race, Ashkenazi ancestry) and genotype with selected clinical features in patients with confirmed chronic visceral and chronic neurovisceral forms of ASMD

开始日期2019-09-27

申办/合作机构

Sanofi

NCT03655223 / Enrolling by invitationN/AIIT

Early Check: A Collaborative Innovation to Facilitate Pre-Symptomatic Clinical Trials in Newborns

Early Check provides voluntary screening of newborns for a selected panel of conditions. The study has three main objectives: 1) develop and implement an approach to identify affected infants, 2) address the impact on infants and families who screen positive, and 3) evaluate the Early Check program. The Early Check screening will lead to earlier identification of newborns with rare health conditions in addition to providing important data on the implementation of this model program. Early diagnosis may result in health and development benefits for the newborns. Infants who have newborn screening in North Carolina will be eligible to participate, equating to over 120,000 eligible infants a year. Over 95% of participants are expected to screen negative. Newborns who screen positive and their parents are invited to additional research activities and services. Parents can enroll eligible newborns on the Early Check electronic Research Portal. Screening tests are conducted on residual blood from existing newborn screening dried blood spots. Confirmatory testing is provided free-of-charge for infants who screen positive, and carrier testing is provided to mothers of infants with fragile X. Affected newborns have a physical and developmental evaluation. Their parents have genetic counseling and are invited to participate in surveys and interviews. Ongoing evaluation of the program includes additional parent interviews.

开始日期2018-10-15

申办/合作机构

Research Triangle Institute

[+16]

100 项与 A型尼曼匹克病相关的临床结果

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100 项与 A型尼曼匹克病相关的转化医学

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0 项与 A型尼曼匹克病相关的专利（医药）

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437

项与 A型尼曼匹克病相关的文献（医药）

2024-03-01·Molecular genetics and metabolism reports

Survival of patients with chronic acid sphingomyelinase deficiency (ASMD) in the United States: A retrospective chart review study.

Article

作者: Ruth Pulikottil-Jacob ; Sumudu Dehipawala ; Brittany Smith ; Amod Athavale ; Gaelle Gusto ; Aastha Chandak ; Artak Khachatryan ; Tamar Banon ; Marie Fournier ; Sophie Guillonneau ; Laurence Pollissard ; Maria Veronica Munoz-Rojas

Background:

Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease type A, A/B, and B, is a rare lysosomal storage pathology with multisystemic clinical manifestations. The aims of this study were to estimate the survival probability in patients in the United States with chronic ASMD (ASMD types B and A/B), and to describe the disease characteristics of these patients.

Methods:

This observational retrospective study included medical chart records of patients with chronic ASMD with retrievable data abstracted by 69 participating physicians from 25 medical centers in the United States. Included patients had a date of ASMD diagnosis or first presentation to a physician for ASMD symptoms (whichever occurred first) between January 01, 1990, and February 28, 2021. Medical chart records were excluded if patients were diagnosed with ASMD type A. Eligible medical chart records were abstracted to collect demographic, medical and developmental history, and mortality data. Survival outcomes were analyzed using Kaplan-Meier survival analyses from birth until death.

Results:

The overall study population (N = 110) included 69 patients with ASMD type B, nine with type A/B, and 32 with ASMD "non-type A" (ASMD subtype was unknown, but patients were confirmed as not having ASMD type A). The majority of patients were male with a median age at diagnosis of 3.8 years. Thirty-eight patients died during the study observation period, at a median age of 6.8 years. The median (95% confidence interval) survival age from birth was 21.3 (10.2; 60.4) years. At diagnosis or first presentation, 42.7% patients had ≥1 ASMD-related complication; splenic (30.0%) and hepatobiliary (20.9%) being the most common, and 40.9% required ≥1 medical visit due to complications.

Conclusion:

Patients with chronic ASMD in the United States have poor survival and significant burden of illness.

2024-01-15·Genes

Differential Interferon Signaling Regulation and Oxidative Stress Responses in the Cerebral Cortex and Cerebellum Could Account for the Spatiotemporal Pattern of Neurodegeneration in Niemann-Pick Disease Type C.

Article

作者: Andrew J Tolan ; Kayla L Sanchez ; Samuel D Shin ; Jacob B White ; Antonio Currais ; David Soriano-Castell ; Christopher G Wilson ; Pamela Maher ; Salvador Soriano

Niemann-Pick disease type C (NPC) is a fatal neurodegenerative condition caused by genetic mutations of the NPC1 or NPC2 genes that encode the NPC1 and NPC2 proteins, respectively, which are believed to be responsible for cholesterol efflux from late-endosomes/lysosomes. The pathogenic mechanisms that lead to neurodegeneration in NPC are not well understood. There are, however, well-defined spatiotemporal patterns of neurodegeneration that may provide insight into the pathogenic process. For example, the cerebellum is severely affected from early disease stages, compared with cerebral regions, which remain relatively spared until later stages. Using a genome-wide transcriptome analysis, we have recently identified an aberrant pattern of interferon activation in the cerebella of pre-symptomatic Npc1^-/- mice. Here, we carried out a comparative transcriptomic analysis of cerebral cortices and cerebella of pre-symptomatic Npc1^-/- mice and age-matched controls to identify differences that may help explain the pathological progression within the NPC brain. We report lower cerebral expression of genes within interferon signaling pathways, and significant differences in the regulation of oxidative stress, compared with the cerebellum. Our findings suggest that a delayed onset of interferon signaling, possibly linked to lower oxidative stress, may account for the slower onset of cerebral cortical pathology in the disease.

2023-12-27·Clinical psychology & psychotherapy

Personality disorder type only sometimes matters: An exploration of patient's personality disorder as a source of variance in early therapeutic alliance.

Article

作者: Tomasz Prusiński

OBJECTIVE:

The study aimed to analyse personality disorders among patients in the early phase of psychotherapy as a source of variance in the quality of the emerging alliance.

METHODS:

The sample consisted of 131 individual psychotherapy patients with borderline (BPD), narcissistic (NPD), dependent (DPD) and obsessive-compulsive (OCPD) personality disorders and 131 psychotherapists. Different sources of alliance estimation were included. Therapeutic alliance was operationalized on several dimensions. The hypothesis was tested using an independent samples one-way analysis of variance.

RESULTS:

The study revealed a significant effect of personality disorder type on early therapeutic alliance quality. BPD patients rated their early alliance the lowest compared to NPD, DPD and OCPD patients. This trend was dominant and replicated regardless of who rated the alliance and which dimension of alliance was estimated.

CONCLUSIONS:

NPD, DPD and OCPD patients have better initial therapeutic alliances than BPD patients, and their alliances do not differ significantly. BPD patients build weaker alliances, and what poses a challenge for them is not only developing a strong and close bond but also conceptualizing goals and reaching agreement on tasks.

项与 A型尼曼匹克病相关的新闻（医药）

2021-02-26

·BioSpace

PicnicHealth and Wylder Nation Foundation Announce ASMD Accelerate to Contribute to Acid Sphingomyelinase Deficiency Research

SAN FRANCISCO & SCOTTSDALE, Ariz.--(BUSINESS WIRE)-- PicnicHealth, the venture-backed startup giving patients unprecedented access to their medical records and the ability to contribute to scientific research, and Wylder Nation Foundation, an organization committed to advancing research for Acid Sphingomyelinase Deficiency (ASMD), are announcing a partnership to generate a real-world ASMD dataset to contribute to medical research. Together, PicnicHealth and Wylder Nation Foundation are forming “ASMD Accelerate,” to understand patient journeys documented in medical record data and translate them into an actionable, de-identified dataset to advance ASMD research. ASMD Accelerate is initially focused on chronic neurovisceral forms of ASMD, commonly referred to as Niemann-Pick Disease Type A (NPA) and Type A/B (NPA/B). ASMD Accelerate centralizes medical records for those living with ASMD or those who have passed away from ASMD. Data from these records will be de-identified and analyzed by Wylder Nation and other researchers to better understand how ASMD progresses over time and how it is managed. Ultimately, the goal is that this data will lead to better care, a better understanding of ASMD, and new treatments. PicnicHealth has helped tens of thousands of patients with chronic or complex illnesses navigate the healthcare system via their patient product. Through the PicnicHealth Research Platform, the company is working with top life sciences, academic institutions, and advocacy organizations to structure anonymized and aggregated medical records, giving researchers access to longitudinal real-world datasets. “Unlocking patient control of medical data is especially important for rare diseases where the data can be incredibly powerful for both clinical care and powering research when too often little is known about the disease,” said Noga Leviner, CEO PicnicHealth. “We couldn't be more excited to partner with Wylder Nation Foundation, patients, and their families.” “Adequately caring for a child with ASMD typically requires the ongoing involvement of multiple physicians associated with different hospitals and academic institutions, creating challenges for families to access and organize their complete medical history,” said Steven Laffoon, Co-founder and President of Wylder Nation Foundation. “This partnership with PicnicHealth will not only help families overcome this barrier but will also lay the groundwork for real-world evidence-based data to help us better understand the true burden of this complex disease, and ultimately help accelerate future treatment options.” Wylder Nation Partnership Leverages Data to Benefit Patients, Their Families, and ASMD Researchers This partnership centralizes medical records for patients and their families. Additionally, it allows Wylder Nation and ASMD researchers to access valuable, anonymized information from medical records that was previously inaccessible. PicnicHealth uses a patient-centered approach and believes keeping patients and their families at the center of research is critical to ensuring patients control their data. In the future, ASMD researchers will be able to apply to access the anonymized dataset for various research projects. Advancing Medical Research with Machine Learning PicnicHealth uses advanced human-in-the-loop machine learning (HITL ML) to digitize and structure complete medical records, including unique details like notes, imaging, and lab records directly from patient providers. PicnicHealth can get records from any facility in the US, in any format, regardless of hospital system or what electronic medical record system they use. Their proprietary algorithm “reads” the records and a nurse validates each abstraction. This approach allows the company to process records at scale while ensuring regulatory-grade accuracy and improving the algorithm with each record. About PicnicHealth PicnicHealth is a healthcare technology company that partners with patients, porting their complete medical records into an easy-to-use online application. The platform gives patients unprecedented access to and control over their medical records and, with their consent, the opportunity to contribute this valuable data to further scientific research. Founded in 2014 by Noga Leviner and Troy Astorino, the company partners with several of the world’s largest biopharma companies and academic research institutions. Learn more at PicnicHealth.com. About Wylder Nation Foundation Wylder Nation Foundation is committed to improving the lives of children and families living with Acid Sphingomyelinase Deficiency (ASMD). Founded in 2013, the organization is focused on fostering collaboration among academic researchers, industry, and other stakeholders to accelerate the discovery and development of treatment options for ASMD and other similar Lysosomal Storage Diseases.

合作