The CurePSP Genetics Program

Обзор

This study is an observational, prospective genetic study. It aims to obtain DNA for research and testing from patients with PSP, CBS, MSA, and related neurological conditions and their families. Up to 1,000 adults who have been clinically diagnosed with PSP, CBS, MSA, or related neurological conditions will be enrolled. The study intervention involves sequencing of participant blood samples using non-CLIA-approved whole genome sequencing at the National Institutes of Health. Pathogenic variants that are deemed possibly related to these conditions will be confirmed using CLIA-approved testing. The study involves minimal risk to participants.

Подробное описание

Genetic research is important for basic, translational, and clinical researchers, and are particularly important for rare disease investigations. Understanding a patient's genetic background may also facilitate participant recruitment for targeted genetic therapeutic trials and has the potential to empower participants with PSP, CBS, MSA, or related neurological diseases and clinicians to make more informed decisions about their clinical care plan. Furthermore, genetic research augments the clinical counseling process by offering participants and their families a clearer understanding of disease risk in relatives. Overall, this study may help to refine current diagnostic criteria for PSP, CBS, MSA, and related neurological conditions, inform genetic counseling, fuel future research studies, and provide insights into potential therapeutic paradigms.

Вмешательства

• Другое Whole genome sequencing will be performed at the NIH
  All samples will undergo non-CLIA approved whole genome sequencing on a research basis in collaboration with Sonja Scholz, MD, PhD at the Neurodegenerative Diseases Research Unit of the National Institutes of Health (Bethesda, MD). This sequencing method allows for the identification of not only variants known to be associated with these disorders but also potentially novel variants.

Первичные конечные точки

• Whole genome sequencing [Срок оценки: 5 years]

Критерии участия

Критерии включения

• Adults (aged 35 or older) with a clinical diagnosis of PSP, CBS, MSA, or a related neurological disease as confirmed by their healthcare provider, or unaffected family members of participants who have reported a family history of relevant neurodegenerative conditions.
• Meet Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Possible or Probable PSP (32), clinically established or clinically probable MSA (33), Armstrong criteria (2013) for possible or probable CBS (34). Diagnostic certainty will be determined by the treating/referring clinician.
• Willingness to undergo genetic testing. Participants will have the option to receive relevant genetic test results.
• Have the capacity to give full informed consent in writing or electronically, or provide consent through a legally authorized representative (LAR)/power of attorney (POA), and have read, understood, and completed the informed consent form.
• Are able to perform or have a designee who can perform study activities (including completion of either online or orally administered surveys).

Критерии исключения

• Individuals who have received a blood transfusion within the past 3 months.
• Individuals who have active hematologic malignancies such as lymphoma or leukemia.
• Individuals who have had a bone marrow transplant within the past 5 years.
• Individuals under the age of 35 or age of majority in applicable states at the time of consenting.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Massachusetts General Hospital — Boston

Публикации

• Jabbari E, Koga S, Valentino RR, Reynolds RH, Ferrari R, Tan MMX, Rowe JB, Dalgard CL, Scholz SW, Dickson DW, Warner TT, Revesz T, Hoglinger GU, Ross OA, Ryten M, Hardy J, Shoai M, Morris HR; PSP Genetics Group. Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study. Lancet Neurol. 2021 Feb;20(2):107-116. doi: 10.1016/S1474-4422(20)30394-X. Epub 2020 De PMID 33341150
• Chen JA, Chen Z, Won H, Huang AY, Lowe JK, Wojta K, Yokoyama JS, Bensimon G, Leigh PN, Payan C, Shatunov A, Jones AR, Lewis CM, Deloukas P, Amouyel P, Tzourio C, Dartigues JF, Ludolph A, Boxer AL, Bronstein JM, Al-Chalabi A, Geschwind DH, Coppola G. Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerativ PMID 30089514
• Hoglinger GU, Melhem NM, Dickson DW, Sleiman PM, Wang LS, Klei L, Rademakers R, de Silva R, Litvan I, Riley DE, van Swieten JC, Heutink P, Wszolek ZK, Uitti RJ, Vandrovcova J, Hurtig HI, Gross RG, Maetzler W, Goldwurm S, Tolosa E, Borroni B, Pastor P; PSP Genetics Study Group; Cantwell LB, Han MR, Dillman A, van der Brug MP, Gibbs JR, Cookson MR, Hernandez DG, Singleton AB, Farrer MJ, Yu CE, Golbe PMID 21685912
• Rohrer JD, Paviour D, Vandrovcova J, Hodges J, de Silva R, Rossor MN. Novel L284R MAPT mutation in a family with an autosomal dominant progressive supranuclear palsy syndrome. Neurodegener Dis. 2011;8(3):149-52. doi: 10.1159/000319454. Epub 2010 Sep 14. PMID 20838030

Идентификаторы

NCT: NCT06647641 · 2024P001971

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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