Clinical Biomarkers in Alpha-mannosidosis
Клучни зборови
Апстракт
Опис
Alpha-mannosidosis (AMD) is an inherited lysosomal storage disorder caused by mutations in the LAMAN gene, which encodes lysosomal alpha-mannosidase and is characterized by neurodevelopmental delay, mild immune deficiency, facial and skeletal abnormalities, hearing impairment, intellectual disability, muscle weakness and ataxia. The progression of neuromuscular and skeletal deterioration is insidious, occurring over several decades, rendering most patients wheel-chair dependent. No consistently successful treatment is available. To better characterize the biochemical phenotype and natural history of this disorder, we will study 15 patients with AMD, ranging in age from five to 60 years, recruited from Departments of Biochemical Genetics and Medical Genetics at university medical centers mainly in the US and Canada or referred by the Intl Society for Mannosidosis & Related Diseases. Participants in the study will visit the NIH Clinical Center 2-3 days on an outpatient basis and will undergo clinical and biochemical evaluations to establish reliable clinical
benchmarks and to identify cerebrospinal fluid biomarkers that could serve as candidate
surrogate markers of treatment effect in future clinical trials. The protocol will take advantage of the NICHD Biomedical Mass Spectrometry Facility to generate CSF proteomic profiles. Patients will also undergo MR spectroscopy (under sedation/anesthesia, if appropriate) in order to establish the phenotypic baseline and for possible utility as a guide for natural history and/or treatment outcomes in future studies. If the pre-clinical components of this proposal prove promising, the prospect of a recombinant adeno-associated viral gene therapy trial involving a brain-directed (intrathecal) approach for AMD would be possible within 3 years.
Датуми
| Последен пат проверено: | 11/28/2019 |
| Прво доставено: | 05/14/2014 |
| Поднесено е проценето запишување: | 05/14/2014 |
| Прво објавено: | 05/18/2014 |
| Последното ажурирање е доставено: | 11/29/2019 |
| Последно ажурирање објавено: | 12/02/2019 |
| Крај на датумот на започнување на студијата: | 07/23/2014 |
| Проценет датум на примарно завршување: | 11/28/2019 |
| Проценет датум на завршување на студијата: | 11/28/2019 |
Состојба или болест
Фаза
Критериуми за подобност
| Возраст подобни за студии | 5 Years До 5 Years |
| Полови квалификувани за студии | All |
| Метод на земање примероци | Non-Probability Sample |
| Прифаќа здрави волонтери | Да |
| Критериуми | - INCLUSION CRITERIA: 1. Must have a verifiable diagnosis of AMD based on clinical, biochemical and/or molecular grounds, including increased urinary excretion of mannose-rich oligosaccharides, decreased acidic -mannosidase activity in leukocytes or other nucleated cells, and/or mutations in two alleles of the LAMAN gene. 2. Must be at least five years old. EXCLUSION CRITERIA: 1. Significant systemic or major disease including congestive heart failure, coronary artery disease, cerebrovascular disease and pre-existing or recent onset pulmonary disease, renal failure, organ transplantation, decompensated liver disease, serious psychiatric disease, or malignancy that in the opinion of the investigator would preclude successful participation.. 2. Pregnancy. We will perform a urine pregnancy test on all post-menarcheal female subjects on the same day as the history and physical exam, prior to MRI. If pregnancy is identified, we will follow Maryland state law in place at the time concerning parental notification. In the event a woman becomes pregnant during the study, she will be withdrawn from all study procedures, but the study team will follow up with the participant regarding the pregnancy outcome. |
Исход
Мерки на примарниот исход
1. Identify cerebrospinal fluid biomarkers that could serve as candidate surrogate markers of treatment effect in a future clinical trial. [Baseline]
Секундарни мерки на исходот
1. Establish reliable clinical benchmarks for alpha-mannosidosis. [Ongoing]
