Vitamin A Transporter Helps Protect Against ALS, German Study Suggests


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Dorothee Dormann, Young Researcher award

High levels of a protein that transports vitamin A through the body helps protect against the development and progression of ALS, a German study suggests.

The protein, retinol binding protein 4 (RBP4), is secreted by fat tissue. The study’s findings suggest it is a potential target for a therapy that could prevent and treat ALS.

Researchers published the work, titled “Association of Serum Retinol-Binding Protein 4 Concentration With Risk for and Prognosis of Amyotrophic Lateral Sclerosis,” in the journal JAMA Neurology.

ALS is the most common motor nerve disease. Although the exact causes are not fully understood, scientists believe both environmental and genetic factors are involved.

Vitamin A, an essential nutrient, plays an important role in brain development. Retinoic acid, the body’s most active form of vitamin A, is a key factor in motor nerve development and motor nerve activity.

The number of retinoic acid receptors decrease during ALS progression, leading to degeneration of motor nerves in mice with vitamin A deficiency, research shows.

Vitamin A is transported throughout the body by RBP4, which also acts as a signaling protein.

Higher levels of RBP4 are also linked to impaired insulin activity, obesity, insulin resistance, and diabetes. Some studies suggest that ALS occurs less in people with higher body mass indices or with diabetes.

These findings have indicated that RBP4 appears to work in two pathways potentially involved in ALS, although the possible link has remained undetermined.

A team of researchers decided to see if there was a link between RBP4 and the risk and prognosis of ALS. They used data from the ALS Registry Swabia, a database of newly diagnosed ALS patients in Swabia, a southern region of Germany.

The study included 289 patients with ALS (mean age 65.7 years), and 504 controls (mean age 66.3 years). Blood samples, medical and demographic data were collected from the  participants.

ALS patients appeared to be leaner, less educated, more prone to smoking, do lighter work, and to have less diabetes than controls. They also had lower levels of RBP4 in their blood.

High levels of RBP4 were significantly associated with decreased odds of developing ALS, suggesting that RBP4 may have a protective effect against the disease.

Among 279 ALS patients who were followed for a median of 14.5 months, higher levels of RBP4 were associated with increased survival.

The team noted that further research is needed to verify whether RBP4 can protect against ALS, and whether any protective effect occurs through the vitamin A or insulin pathway — or both.

If future studies confirm the associations, RBP4 “may represent a possible target toward prevention and treatment of ALS,” the researchers wrote.