With the objective of developing a therapy that stops the progression of Niemann Pick Type C, a serious and rare disease, mainly affecting children, researchers from the Catholic University and the Center for Aging and Regeneration, CARE Chile UC are leading a series of studies. The findings are relevant since this genetic pathology causes progressive damage affecting the full mobility of patients, who usually die at the beginning of the second decade of life.

Dr. Alejandra Álvarez, researcher at the Center for Aging and Regeneration of the Catholic University of Chile, CARE Chile UC.

Dr. Alejandra Álvarez, researcher at the Center for Aging and Regeneration of the Catholic University of Chile, CARE Chile UC.

Doctors Alejandra Álvarez and Silvana Zanlungo, from the Schools of Biological Sciences and Medicine,respectively, analyzed experimental models of this disease, discovering the presence of a cell signaling pathway , also present in Alzheimer’s, whose main component is a protein called ABL. In that context, they observed that by inhibiting this protein, therapeutic effects were generated in the study animals.

Stopping the disease

“Our research has helped determine that by working with this signaling pathway it is possible to slow the progression of this deadly pathology, which in its most common form affects healthy children between the ages of 3 and 4, who begin to lose neurons associated with the control of movement. Those who suffer from it end up prostrate before puberty. Along with stopping the progression of symptoms we have increased life expectancy in animal models and in the near future we want to deliver an effective treatment to patients,” says Dr.  Alejandra Álvarez, a researcher at the Center for Aging and Regeneration of the Catholic University, CARE Chile UC. These studies are conducted in collaboration with the US National Institute of Health.

“We have observed that if we inhibit the ABL protein we can slow the progress of the disease. With that we do not think we are solving the problem in its entirety, but we are giving a better opportunity for life and survival to the study models, which we hope will translate into future well-being for patients,” adds the biochemist and doctor in Cellular and Molecular Biology.

Lysosomal accumulation

The lysosome is a specialized cell structure that contains numerous enzymes and has the function of degradation and recycling of nutrients. “This organelle is a center in which components are recycled, a process of great importance for obtaining new nutrients,” says Dr. Álvarez.

Dr. Alejandra Álvarez in her laboratory at Centro UC CARE.

Dr. Alejandra Álvarez in her laboratory at Centro UC CARE.

The researcher explains that Niemann Pick affects all cells. However, the most sensitive are neuronal cells. “The human body has enzymes that cleanse the body of substances. When this function fails a toxic state originates. In the case of this disease there is a lysosomal accumulation of cholesterol in some peripheral tissues such as the spleen and liver.”

Patients affected with this genetic condition begin to have difficulty moving in a normal way, and later manifest speech disorders, until they are completely dependent on their family environment.

Effective therapy

To combat Niemann Pick, a drug called Miglustat is currently being used that inhibits the synthesis of glycosphingolipids, which accumulate in this disease and whose use arises from other diseases of lysosomal accumulation. Another therapy that is under development is cyclodextrin, and it has been shown to be able to remove cholesterol from cells.

“The problem with these treatments is that they work very well in the peripheral system, but not very well in the brain. This is because they get past or very little passes a barrier called the blood-brain barrier, whose function is to protect this organ from the ingress of unusual or harmful substances. Therefore, the great challenge for any neurodegenerative disease is to overcome this barrier, and the great problem of cyclodextrin is that it does not reach the brain or it does so in a very low proportion,” explains the researcher at CARE Chile UC.

“What we are doing is looking for new inhibitors that have the possibility of crossing the blood-brain barrier and in the future, can become an efficient therapy for the disease. We already have some substances that are potential drugs for the treatment of Alzheimer’s and Niemann Pick, both of which are in the pre-clinical stage.”

Rare disease

The academic of the Catholic University says that Niemann Pick has low prevalence worldwide, being considered in the group of rare diseases. Additionally, the lack of an organized diagnostic method has prevented accurate knowledge of the number of people affected by this disease.

“In Chile, we do not know if there is a record of the diagnosed cases. Pediatricians in general are not very aware of this pathology, because it is a rare disease and difficult to diagnose.

International financing

Dr. Alvarez said that despite not being a very prevalent disease, it turns out to be a devastating disease, especially considering that it attacks children very aggressively.

“Globally, it does not generate large interest from pharmaceutical companies, but there are foundations and research institutes that are interested. It is usually the families of the affected children who raise funds to study the disease. We have long been funding the Ara Parseghian Foundation, and now another US foundation, the University of Pennsylvania is funding us,” she explains. Together with this support they have also received the support of Fondecyt and Fondef for the projects that they have acomplished so far. (By: María Mercedes Barraza C. Agency: Inés Llambías Communications).

See here video where Dr. Alejandra Alvarez refers to this topic: