Lead Exposure and Multiple Sclerosis

Lead Exposure and Multiple Sclerosis;Biomarker Evidance and Clinical Impact.

1. To evaluate the effect of lead level on the pathogenesis of multiple sclerosis
2. Measure lead in blood sample of study groups
3. Estimate the expression level of DNA methyltransferase.
4. Evaluate oxidative stress markers, like MDA/8-OHdG
5. Measureδ-aminolevulinic acid
6. Correlate the clinical data of patients with biochemical markers

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis

Detailed Description

inflammation, demyelination, gliosis, and neuronal loss are all components of multiple sclerosis (MS), a chronic autoimmune disease that affects the central nervous system (CNS). Myelinated axons in the CNS are the target of MS attacks, which can cause varying degrees of damage to both myelin and axons.MS affects 2.3 million people worldwide. MS is often diagnosed between the ages of 20 and 50 years, with females experiencing it more often than males. Four MS phenotypes exist: clinically isolated syndrome, relapsing-remitting (RRMS), secondary progressive and primary progressive.Many factors have been found to be associated, including environmental toxins..Pathological features that require explanation are the presence of demyelination in both white and grey matter , the targeting of oligodendrocytes, damage to the blood-brain barrier, inflammation in MS plaques and in the meninges, astrocyte activation, the central role of blood vessels and their perivascular spaces, and the presence of oxidative stress, mitochondrial damage, and oligodendrocyte apoptosis.Oxidative Stress and MS

.the oxidative damage of oligodendrocytes and neurons is associated with inflammation, and play a major role in neurodegeneration.Many autopsy studies describe an increase in various markers of lipid peroxidation, markers of DNA damage.CSF levels of trace metals involved in oxidative stress processes were the subject of a single study, which described increased lead, decreased magnesium, and similar calcium, manganese, and zinc levels in patients with primary progressive MS (PPMS) compared to those with secondary progressive MS (SPMS) and controls. lead(Pb) is a well-known toxic metal that threatens public health and is widely involved in the pathogenesis of MS. Accumulation of Pb in cells has been associated with the development of autoantibodies against different cellular structures such as neurofilaments, neuronal cytoskeletal proteins, and myelin basic protein.Lead exposure primarily occurs through ingesting tainted food or water, or inhaling Pb-contaminated air.The primary sources of occupational Pb exposure include the production of paint, recycling of batteries, wood preservation, welding, textile, printing, and handicraft industry . Some other sources, like canned food, cosmetics, lead pipes for water supply, and use of herbal products, also lead to Pb exposure in humans.The specific pathophysiological mechanisms mediating the relationship between environmental risk factors and MS susceptibility remain unknown, and DNA methylation may provide information on these mechanisms.This epigenetic pathway contributes to various MS pathophysiological processes, such as demyelination and remyelination, inflammatory response, and the collapse of the blood brain barrier (BBB).Research shows that lead has a deleterious impact on the immune system and is an important factor in inflammation. Lead also impacts cytokine metabolism (interleukins IL-1b, IL-4, IL-2, IL-8, and IL-6), TNF-α and INF-γ, and the expression of inflammatory enzymes (cyclooxygenases). Numerous studies have examined the impact of lead on immune system cells, including macrophages, B and T lymphocytes, and Langerhans cells. However, the impact depends on the kind of lead, dosage, route of entry, exposure period, age, host and genetic predisposition.Mechanisms by which lead may contribute to MS pathogenesis

1. oxidative stress (increased reactive oxygen species (ROS)/ malonyldialdehyde( MDA)/[8-Hydrox-2-deoxyguanosine( 8-oHdG)])
2. Immune system dysregulation (activation of microglia/shift toward pro-inflammatory cytokines IL-6,TNF-a)
3. Blood brain barrier disruption (lead increase BBB permeability)
4. Epigenetic effects (effect DNA methyltransferase/altered gene expression lead to autoimmunity) Therefore, studyig the effect of lead exposure on pathogenesis of multiple sclerosis is of great importance.

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: Asmaa Mohammed Aref, domenestrator; Phone Number: +201012061829; Email: asmaaaref@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

20-50 years old ,matched age ad sex

Description

Inclusion Criteria:

• patients aged20-50 years diagnosed MS patients according to Mc Donald criteria

Exclusion Criteria:

• other autoimmune disease Chronic renal or liver disease

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
healthy group
multiple sclerosis group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measure concentration of blood lead level in multiple sclerosis patients and controls, assessed with biochemical analysis	2years
Measure levels of oxidative stress markers like MDA/8-OHdG assay using biochemical analysis.	2years
Measure levels of DNA methyl transferase expression level (evaluate oxidative stress-mediated epigenetic change) using PCR.	2years
Measure δ-aminolevulinic acid levels via biochemical analysis.	2years

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Ragaa Hamdy Mohamed Salama, prof., Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): May 5, 2029

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis
• Other Study ID Numbers: lead and multiple sclerosis

Plan for Individual participant data (IPD)

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