Pleiotropy and Mechanism of Peripheral Nerve Related Genes in the Progression of Amyotrophic Lateral Sclerosis

This study will establish a comprehensive exon database of ALS patients, lay the foundation for screening the genes related to the occurrence and development of the disease, support the theory of ALS disease progression from peripheral to central, and reveal the correlation between the functional level of peripheral nerve and the prognosis of the disease at the gene level for the first time, and provide the basis for the mechanism research at the molecular level.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Diagnostic test: Patient information collection, exon sequencing and follow-up.

Detailed Description

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively invades superior and inferior motor neurons. Because there is no effective treatment, it is urgent to find the risk factors of ALS to guide the prevention and slow down the disease progression. In the early stage of the disease, the peripheral motor injury is more rapid and sensitive than the central response, which is an ideal window to observe the state of the disease. Protecting peripheral nerve integrity and maintaining its function can slow down the death of superior neurons, effectively relieve symptoms and prolong survival time, which has also been confirmed in patients with multiple stem cell-derived motor neurons and SOD1 G93A disease model mice. Reexamination of the role of peripheral motor nerve related factors in the development of ALS is of great significance for the study of disease mechanism, clinical classification, prognosis, evaluation of drug trial efficacy and individualized treatment plan. Previous studies have shown that NEFL gene, as the coding gene of light chain of neuron cytoskeleton, is closely related to axonal function, and its polymorphism is related to the occurrence and severity of axonal Charcot Marie Tooth disease. Exploring the role of similar peripheral nerve related genes in the progression of ALS will help us better understand the disease from the genetic level, establish an accurate and stable prognosis prediction model, and guide early treatment. This study will establish a comprehensive exon database of ALS patients, lay the foundation for screening the genes related to the occurrence and development of the disease, support the theory of ALS disease progression from peripheral to central, and reveal the correlation between the functional level of peripheral nerve and the prognosis of the disease at the gene level for the first time, and provide the basis for the mechanism research at the molecular level.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100098
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Amyotrophic lateral sclerosis patients in Peking University Third Hospital

Description

Inclusion Criteria:

1. Since February 2021, he has been in the Department of Neurology, the Third Hospital of Beijing Medical University. He was diagnosed amyotrophic lateral sclerosis according to the revised EI Escorial diagnostic criteria of 2004 edition, and the patients within one year of onset.
2. Informed consent has been signed.

Exclusion Criteria:

1. Patients with ALS like syndrome caused by autoimmune diseases, paraneoplastic syndrome and simple demyelinating lesions were excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Amyotrophic lateral sclerosis patients group	Diagnostic test: Patient information collection, exon sequencing and follow-up.; Clinical baseline data, disease characteristics, auxiliary examination results, EMG examination results, drug use and other information were collected. 4-6ml peripheral blood was collected for exon sequencing. The patients were followed up every three months by a specialist in the form of outpatient or telephone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death	patients' death	until the patient dies, usually 1-10 years after diagnosis.
invasive breathing	The patient uses a ventilator to maintain breathing	until the patient has invasive breathing, usually 1-10 years after diagnosis.

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2021
• Primary Completion (Anticipated): August 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: June 27, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 8, 2021

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: M2021051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No