Parkinson's disease is a neurodegenerative disease that affects about 150,000 Spaniards, about 2,400 of them from Navarre. It is estimated that 2% of people over 65 years of age suffer from it. This pathology is caused by the progressive death of dopaminergic neurons, brain cells responsible for the motor function of the organism. At a certain moment, and for reasons still unknown, a protein called alpha-synuclein begins to accumulate and malfunction in these neurons, which is the apparent ultimate cause of the death of these neurons.

In the last 20 years, the research in Parkinson's disease has focused on trying to alleviate the effects of the disease or to slow its progression. These efforts, more or less effective, were aimed at improving the patient's quality of life. No hypothesis raised possible glimpses of a curative treatment... until now.

For the last year, academic community has been waiting for the demonstration of the existence of a direct link between a mutation Genetics and a greater predisposition to suffer from Parkinson's disease. This is the GBA1 gene mutation that causes Gaucher disease, a rare disease Genetics , of autosomal recessive inheritance, i.e. it will be suffered by those individuals who inherit this mutated gene from both parents. However, it is considered that 1 in 200 people are carriers of this mutation. Specifically, according to the National Registry of Patients (year 2013), in Spain there are 373 affected and 1,400 carrier relatives, belonging to 273 families.

Among the rare diseases, Gaucher disease is the most frequent of those known as "lysosomal storage diseases". Lysosomes are a part of cells responsible for cellular digestion. Their storage is due to a genetic disorder that causes a deficiency or lack of an enzyme. In Gaucher disease, mutation of the GBA1 gene, responsible for encoding the lysosomal enzyme GCase, causes the accumulation of a substance (glucocerebroside) whose correct degradation is important for the central and peripheral nervous system, being the ultimate manager of the clinical manifestations of the pathology.

In 1939 the first case of a Gaucher patient presenting with parkinsonian symptoms was published. Since then several similar individual cases have been reported but went unnoticed until 1996. Then a study of 6 Gaucher patients was published in which typical parkinsonian symptoms such as resting tremor, rigidity and slowness of movement were observed. This research did have a major impact and prompted another multicenter study with thousands of patients in different hospitals in the United States looking for mutations of the Gaucher gene. The results of this and other programs of study studies along the same lines, published from 2006 onwards, showed that the presence of the mutated GBA1 gene was the main predisposing factor for Parkinson's disease and other related pathologies such as dementia with Lewy bodies. In other words, for the first time a direct link between a rare disease (Gaucher) and a neurodegenerative disease was demonstrated.

Although not all Gaucher patients and not all carriers of the mutated gene develop Parkinson's disease, it is estimated that this rare disease condition increases the risk of developing Parkinson's disease by 20 to 30 times (about 10% of Parkinsonian patients have it). Also, 25% of Gaucher patients have a first-degree relative Degree diagnosed with Parkinson's disease.

To date, it is considered that the mutation in the GBA1 gene, by causing the loss of function of the GCase enzyme, leads to greater aggregation of alpha-synuclein and, therefore, greater neuronal death. These data have motivated great interest from the Michael J. Fox Foundation -a leader in the promotion of the research of this disease- and from different pharmaceutical and biotechnology companies that are committed to designing mechanisms that increase or activate the function of this enzyme and reverse the effects of the accumulation of alpha-synuclein, i.e., prevent the brain cells that cause Parkinson's from dying. In fact, companies such as Sanofi-Genzyme already have phase II clinical trials underway with this goal and other pharmaceutical companies will soon begin to test similar strategies in Parkinsonian patients.

At summary, we are on the threshold of a new generation of Parkinson's treatments that, for the first time, are aimed at trying to slow the progression of the disease to the point that it could be possible to halt progression in the future. In our laboratory of the research center Applied Medicine (CIMA) of the University of Navarra we are working intensively in this direction, counting both with our own resources and with the direct contact with several European and North American pharmaceutical companies that share our hope in the design of these new treatments, which we hope will be a therapeutic reality that will not take long to be applied.