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Sanfilippo syndrome is a rare and intractable neurodegenerative disorder of genetic origin. The first symptoms occur during infancy and lead to premature death in early adulthood. Affected children present mental retardation and physical disabilities that worsen as the disease progresses.
Sanfilippo syndrome is the result of the interrupted degradation of molecules known as mucopolysaccharides in a number of tissues within the organism. Owing to a genetic mutation resulting in an enzyme deficiency, the body becomes unable to eliminate these partially digested molecules, which are toxic, especially for the brain.
The first symptoms of the disease - hyperactivity, sleep disorders and sudden involuntary movements - appear between the ages of 3 and 6 years. Neurological damages subsequently cause intellectual deficiencies and reduced motor skills, leading to a loss of autonomy around 10 years. There is also slight facial dysmorphia. Progressive neurodegeneration causes premature death between the ages of 20 and 30.
Sanfilippo syndrome is under-diagnosed, which makes it difficult to appreciate prevalence. However, the most recent figures estimate the number of affected births between 1 and 3 per 100,000, depending on the country. A French study carried out between 1990 and 2006 indicates 0.68 diagnosed cases per 100,000 births.
Four Sanfilippo sub-types are recognized, known as A, B, C and D. Each corresponds to a different enzyme deficiency. According to European studies to date, sub-type A is more predominant in Northern Europe, while B is more prevalent in the south.
The severity and progression of the symptoms vary according to the sub-type diagnosed. Transmission of the disease is the same for all sub-types. Known as recessive autosomic transmission, it occurs from parent to child: a child has a risk of being affected if both parents carry one of the genetic mutations responsible for the disease.
No curative treatment for Sanfilippo syndrome has been established. However, genetic therapy trials for sub-types A and B are scheduled in humans within the next few years (see the paragraph "At the Institute Pasteur"). These trials aim to correct the enzyme deficiency responsible for the disease by supplying the missing enzyme using a viral vector. For the time being, there is no treatment that can slow the fatal outcome of the disease. However, a multidisciplinary management approach improves the quality of life for the patients and their families. Some of the symptoms of the disease, in particular the behavioral disorders, can be prevented or attenuated with the use of drug treatment and children can undergo sessions with specialist medical support professionals to address motor defects and disorders.
The Neuroscience Department houses the Institut Pasteur/Inserm “Bioterapies for neurodegenerative diseases” joint unit, which conducts research focusing on a number of neurodegenerative diseases. In July 2011 this unit, led by Jean-Michel Heard, developed the first human neuron model for Sanfilippo syndrome derived from induced pluripotent stem cells. This model is the tool of choice for studying the cellular mechanisms at the root of this disease and for identifying therapeutic options. The procedure used by the scientists could also be applied to model other diseases neurodegenerative diseases.
The Institut Pasteur is also promoting a gene therapy trial. This trial has started in October 2013, and focuses on sub-type B of the disease.
Led by Jean-Michel Heard