A Study of Intravenous Immunoglobulin Used to Treat Multiple System Atrophy

 

A study found on Medscape confirms that the human immune system and the human brain are the most complicated in our biological systems. The two systems are responsible for the ability to learn, communicate, and for total recall.

Multiple system atrophy is considered a white matter disorder affecting the nerves that connect parts of the brain and the spinal cord. Issues with balance occur and gradually worsen.

MSA affects about five people in 100,000. MSA can cause parkinsonism and dysautonomia (disorders of the autonomic nervous system) combined with orthostatic hypotension (low blood pressure).

The median survival for MSA patients is six to nine years during which the disease progresses rapidly. Currently, there are no therapies to modify the disease progression. MSA is characterized by various degrees of parkinsonian features and myelin (covers nerve fibers) degeneration together with loss of nerve cells.

In 2007, the American Academy of Neurology and American Autonomic Society determined two categories: MSA-P as predominantly parkinsonism and MSA-C characterized as having predominant cerebellar features.

Another characteristic of MSA is the collection of the a-synuclein (a-syn) protein found in several areas of the brain in early MSA. A-syn is also found in Parkinson’s disease.

The Cause of MSA

Although MSA has been studied for many years, its cause is still unknown. There is evidence, due to the production of toxic cytokines and microglia activation, that neuroinflammation may be responsible for MSA’s neurodegeneration.

For example, cytokine proteins control the growth of cells and help them cope when confronted with inflammation and immune challenges.

As another example, microglia represent the predominant brain cells and are located largely in the spinal cord and brain. Microglia are the brain’s key effector cells and the first line of defense in the central nervous system. These cells are responsible for activating an immune response to defend the body.

The Case for IVIG (Intravenous immunoglobulin)

 Intravenous IVIG has many anti-inflammatory properties. It is a class of proteins found in the immune system that function as antibodies (foreign substances) and produce an immune response. IVIG has been found to be effective in treating several neuroinflammatory and autoimmune disorders.

A clinical study was prepared based on the theory that the neuroinflammatory symptoms in MSA may be altered by the use of IVIG immunoglobulin.

Participants with probable MSA were selected for the study. In addition, participants received brain MRI to eliminate subjects who may have structural abnormalities that mimic MSA. Dementia was also cause for exclusion.

All participants had been previously diagnosed with various combinations of cerebellar syndrome and parkinsonism, a poor reaction to levodopa, urinary incontinence, and autonomic failure meaning their systolic blood pressure would drop ≥ 30 mm Hg after standing for three minutes.

The tolerability and safety of IVIG were the primary measures of the infusions in MSA patients.

The frequency of adverse events (AEs) was considered to be the primary endpoint. This included severity related to IVIG. AEs were assessed during the study and at a minimum of sixty days after the study.

Details of the study are available here.

Plasma From Thousands of People

Due to the anti-inflammatory efficacy of IVIG in autoimmune disorders, IVIG (pooled from thousands of people) has been used for almost three decades. It has won recognition for efficacy in a number of neurological disorders.

Subcutaneous (under the skin) administration is now being used frequently, especially due to the ease of administering IVIG in the outpatient setting. However, as the demand and costs rise, supply shortages are inevitable. New or recombined products are being developed but have not yet been tested in clinical trials.

Cerebellar Findings

One of the following was required:

  • Ataxic gait: abnormal, uncoordinated movements.
  • Cerebellar dysarthia: slurred, choppy, or mumbled speech
  • Cerebellar oculomotor findings:  wide-based, unsteady, lurching walk
  • Limb ataxia: Inability to make smooth, coordinated movements of an arm or a leg,

Additionally, in order to avoid enrollment of non-MSA patients, only patients with all three syndromes (parkinsonism, cerebellar, and autonomic) were enrolled.

Evaluation of IVIG’s efficacy was the secondary measure.

Results: IVIG was well tolerated and appeared be safe. No serious adverse events occurred. It is believed that IVIG may improve functionality in MSA. Researchers recommended a further placebo-controlled trial.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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