Medicine that could improve the life expectancy of those suffering from Niemann Pick type C disease

Under the umbrella of Niemann Pick disease, a heterogeneous group of lysosomal lipid accumulation diseases is included, classified into four subgroups, from A to D. Types A and B (or ASMD) have no treatment. Until now, the only treatment available in Europe is Miglustat, a drug capable of inhibiting the enzyme responsible for the first step in the synthesis of glycosphingolipids, which is limited to the treatment of neurological manifestations in both adult and pediatric patients in types C and D , a variation of type C.

Niemann-Pick type C disease is transmitted by autosomal recessive inheritance, it is neurodegenerative and causes a problem in the transport of cholesterol and sphingolipids in the lysosomes, vesicles of the cells responsible for the trafficking of substances. Thus, there is an accumulation of these lipid substances that make the cell and, more specifically, the synapse, not work well.

Patients can start experiencing symptoms at different ages, from infants to adults. They present very diverse clinical symptoms, usually with involvement of the nervous system and with visceral involvement in the liver, spleen and, in more severe cases, in the lungs and, ultimately, in the brain.

The involvement of the nervous system is highly variable: from cognitive difficulties to behavioral and psychiatric problems, epilepsy, limitation of eye movement, dystonia, ataxia or splenomegaly, among others.

A clinical trial at the Bellvitge University Hospital, as well as at the Bellvitge Biomedical Research Institute (IDIBELL), located in Hospitalet de Llobregat and which is part of the CERCA institution of the Generalitat of Catalonia, is providing new expectations for treatment for patients with Niemann-Pick disease type C.

The study aims to determine the efficacy and safety of the drug known as Efavirenz to help alleviate cognitive impairment and learning and behavior problems, improving the quality of life of patients. It is an antiretroviral drug that has been used against HIV (the AIDS virus) for many years and for which the generic pharmaceutical specialty is already available.

IDIBELL and Bellvitge Hospital are studying in a clinical trial the efficacy of Efavirenz, an antiretroviral against the AIDS virus, against Niemann Pick type C disease. (Photo: IDIBELL / Bellvitge Hospital)

The new therapeutic activity of Efavirenz was discovered within the framework of a basic research project in neurobiology, led by Dr. María Dolores Ledesma, at the Severo Ochoa Molecular Biology Center in Madrid (Spain) between 2014 and 2020. The good response in animals, in which the drug has improved the function of an enzyme that regulates the distribution of cholesterol in the synapse, has opened the hope that it can be transferred to humans.

Translational research has now begun to validate the use of Efavirenz in patients at the Bellvitge University Hospital.

The research is led by the neurologist Jordi Gascón, principal investigator of the IDIBELL Neurological and Neurogenetic Diseases research group and head of the Neurology Service section of the Bellvitge University Hospital (HUB), with the collaboration of the clinical pharmacologist Sebastià Videla, responsible for the HUB-IDIBELL Research Support Unit.

The regulated trial includes the participation of 14 of the 27 patients over 14 years of age diagnosed with type C Niemann-Pick disease in Spain. So far, there is no cure capable of ending Niemann Pick disease (which affects 1 in 150,000 people), since its cause is unknown. The forecast is that the study will last 52 weeks, that is, one year.

The trial has been fully financed from the Juan Girón research grant from the Fundación Niemann Pick España, based in Lleida, which has the support of affected families, friends, volunteers and other collaborators. Homonymous European and international organizations have expressed their desire to replicate the design of this study to carry it out worldwide, with the aim of advancing in many fields of the disease. However, support would have to be secured in order to have the necessary funding to get it off the ground.

“The effective use of Efavirenz in humans will mean greater hope and quality of life for patients and their families, since the mice have improved cognitively, have better behavior and live much longer”, pointed out Dr. Jordi Gascón, coordinator of the clinical trial and member of the Minority Diseases Group of the Bellvitge University Hospital.

“Thanks to the networking of a researcher, a clinician and a pharmacologist expert in regulation, a significant positive impact could be achieved in the lives of families and patients of a disease that is very hard. We have shared the sensitivity to help these families selflessly and non-profit. We hope to have positive results at a local level so that we can share this knowledge with the international research network on Niemann Pick and rare diseases in the near future”, says Dr. Videla, head of the HUB-IDIBELL Research Support Unit. (Source: IDIBELL)