Lopid (gemfibrozil), an FDA-approved lipid-lowering drug, was found to improve life expectancy and motor function in mice with late infantile neuronal ceroid lipofuscinosis (late infantile NCL, or LINCL), which belongs to a group of disorders collectively referred to as Batten disease.
The study, “Gemfibrozil, Food and Drug Administration-approved lipid-lowering drug, increases longevity in mouse model of Late Infantile Neuronal Ceroid Lipofuscinosis,” appeared in the Journal of Neurochemistry.
LINCL is a rare neurodegenerative disease caused by mutations in the Cln2 gene, leading to a deficiency or loss of function of the TPP1 enzyme. The TPP1 deficiency then causes an accumulation of lipid (fat)-protein pigments in the brain, which is a common hallmark of lysosomal storage diseases.
These genetic metabolic diseases result from an abnormal function of the lysosomes, the cellular organelles responsible for the breakdown of large molecules.
Similar to other neurodegenerative disorders, neuroinflammation and neuronal death are seen in LINCL. The onset of symptoms occurs in children from 2 to 4 years old, and despite a continued research effort, no effective treatment is currently available for LINCL patients, who typically die young. Therefore, new therapies capable of significantly extending life expectancy and improving quality of life are greatly needed.
The research team was led by Kalipada Pahan, PhD, a professor in the Department of Neurological Sciences at Rush University Medical Center in Chicago. The scientists used a mouse model of LINCL, deficient in TPP1, to study the therapeutic potential of Lopid, a drug that helps reduce cholesterol and triglycerides levels in the blood. Lopid has also been shown to stimulate neuroprotection and anti-inflammatory responses.
The study revealed that an eight-week oral treatment with Lopid led to a 10-week increase in longevity and to improved motor activity. In addition, Lopid partially decreased the burden of storage materials, increased the levels of anti-inflammatory molecules, and prevented neuronal death in different parts of the brain.
Interestingly, given the TPP1 deficiency in these mice, the results indicate that Lopid’s beneficial effects are independent of TPP1. This is a key finding, as it shows potential toward the development of a treatment to improve aggregate accumulation in the brain of LINCL patients.
Compared to other prospective neuroprotective drugs, Lopid has important advantages because it can be administered orally, it’s fairly nontoxic, and was well tolerated in human and animal studies.
Overall, “our results identify [Lopid] as a possible therapeutic agent to prolong the lifespan in LINCL patients,” the researchers wrote.