The fat-lowering therapy gemfribrozil decreased disability and increased the lifespan of mice with a form of Batten disease that strikes children, according to a preclinical-trial study.
The finding suggests the high-cholesterol drug could be used to treat children with Batten, which scientists call Neuronal Ceroid Lipofuscinosis, or NCL. The research also indicated the therapy is safe for children.
The study, “Safety and potential efficacy of gemfibrozil as a supportive treatment for children with late infantile neuronal ceroid lipofuscinosis and other lipid storage disorders,” was published in the Orphanet Journal of Rare Diseases.
NCL refers to a group of disorders caused by mutations in genes that help turn lipids, or fats, into energy. Scientists have linked a number of genes to the disease. Most play a role in the lysosomal pathway that regulates metabolism.
Because NCL involves a number of mutations, it has been difficult for scientists to come up with a therapy that can treat the patient population as a whole.
Researchers are using animal models to investigate a number of approaches. They are treating a type of NCL known as late infantile classic juvenile with enzyme replacement therapy, for example—replacing a mutated version of the CLN2 enzyme with a healthy one.
Other treatment methods they are exploring include gene therapy, gene editing, and using small molecules and stem cells.
Since NCL is a family of diseases with different genetic backgrounds, one therapy is unable to handle all cases. Another complication is that by the time a doctor diagnoses NCL, the disease may have progressed to the point that a particular treatment won’t work.
In addition, some therapies are invasive—that is, they have impacts on the body that go beyond treating the disease. That makes parents hesitant to put children on them.
The lipid-lowering drug gemfibrozil has proven effective as a treatment for NCL in animals.
The U.S. Federal Drug Administration approved it in 1976 to reduce lipid levels in blood serum. Gemfibrozil activates peroxisome proliferator-activated receptor-alpha (PPARα). That receptor is part of a molecular mechanism that leads to fat metabolism, which allows the body to rid itself of lipids.
Gemfibrozil also reduces inflammation, bolsters nerve-signal transmission and increases the production of lysosomal proteins, which are mutated in NCLs.
The drug increased the lifespan of mice with late infantile classic juvenile NCL, delayed the onset of disabilities associated with the disease, and reduced the animals’ lipid levels, researchers discovered.
Gemfibrozil leads to weight gain, a side effect that would need to be closely monitored.
Other researchers have used gemfibrozil to lower lipid levels of children with other disorders, such as hyperlipidemia, or high cholesterol. Only three of 200 children who received gemfibrozil for hyperlipidemia experienced adverse events, indicating the drug is safe for children.
The bottom line is that gemfibrozil is an attractive alternative to invasive therapies that scientists are studying, and could be used in combination with them, the research team said. They concluded that gemfibrozil is safe and may be able to delay the progression of NCLs.