Rare Genetic Disorder Given Hope with New Drug Delivery System

A nanotech-based delivery system was found to improve treatment and reduce side effects in patients with Neimann Pick Type C1 (NPC1) disease, according to a recent study published in Scientific Reports.

NPC1 is a rare progressive genetic disorder that results in abnormal cholesterol accumulation in various tissues of the body, leading to progressive neurodegeneration and eventual death. According to the National Organization for Rare Disorders (NORD), 1 in every 100,000 to 120,000 children are affected by this disease.

“Right now there’s nothing that can be done for patients with this disease, and the median survival time is 20 years,” said corresponding study author Gaurav Sahay.

Although there are no approved drugs for this disease, the investigational drug cyclodextrin (HPβCD) is currently undergoing clinical trials and shows promise. Unfortunately, a major drawback of this medication is that it requires high doses that cause significant hearing loss and lung damage.

Furthermore, treatment is administered by injecting the drug directly into the brain. In the new study, researchers outlined the potential for a nanotech-based delivery system that could carry the HPβCD drug into cells more effectively.

Furthermore, it could also help improve the efficacy of the drug by approximately 5 times, and allow for doses to potentially be administered in lower doses to help treat the disease without causing side effects, according to the study.

“The new cholesterol-scavenging drug proposed to treat this disorder, called cyclodextrin or HPβCD, may for the first time offer a real treatment,” Sahay said. “But it can cause significant hearing loss and require multiple injections directly into the brain, which can be very traumatic. I’m very excited about the potential of our new drug delivery system to address these problems.”

This new method involves attaching the HPβCD drug to an extraordinarily small, nanotech-sized lipid particle that can carry the drug into cells, where it helps to flush out cholesterol. However, surprising results from the study revealed that the carrier itself also helped address the issue, while working in synergy with the HPβCD drug, which helped to increase its efficacy.

These findings show that the delivery method should allow for the use of much lower dosages of the drug, and could potentially be delivered through intravenous injection instead of brain injection, which would be a much easier delivery process for the patient. In prior studies of the HPβCD drug in animal models, the treatment was able to slow the progression of NPC1, but could not reverse it.

The authors noted that this drug delivery method has several advantages, including prolonged circulation times, incorporating multiple drugs with different mechanisms of action, and a variety of targeting ligands that can help cross the blood brain barrier.

“Taken together, nanocarriers can serve as a platform that can effectively deliver small molecules, genes, and perhaps imaging agents for treatment and diagnosis of a wide variety of other rare lysosomal storage disorders,” the study authors said.