There are several approaches being investigated for the treatment of Sanfilippo. Whilst the cause of the disease is fairly well understood (the presence of mutated genes prevents the body from producing the enzyme necessary to recycle waste), treating the disease presents researchers and clinicians with a number of challenges.


There are several approaches being investigated for the treatment of Sanfilippo. Whilst the cause of the disease is fairly well understood (the presence of mutated genes prevents the body from producing the enzyme necessary to recycle waste), treating the disease presents researchers and clinicians with a number of challenges. One of the main challenges resides in the neuro-degenerative nature of the disease. Because Sanfilippo mostly affects the Central Nervous System (CNS), the administration of an effective treatment is challenged by the inability of most drugs to cross the Blood-Brain-Barrier (BBB) and enter the brain. The BBB is a natural filter that protects the brain and stops toxins and pathogenic agents present in the blood from entering. This makes traditional intravenous administration ineffective for most therapeutical products which can travel through the bloodstream but not cross the BBB.

The different approaches researched all try to address the recycling problem and disease symptoms in a different way. To date, Gene Therapy (GT) and Enzyme Replacement Therapy (ERT) represent the most advanced and promising avenues for finding a treatment for Sanfilippo patients.

Gene Therapy (GT)

What is it?

Gene Therapy is a treatment approach that involves introducing genetic material into a person’s cells to fight or prevent the disease. Gene Therapy has been researched for more than 20 years with over 1,000 human clinical trials conducted for many genetic conditions such as severe combined immuno-deficiencies, haemophilia, Parkinson’s disease, cancer and even HIVs.

A gene can be delivered to a cell using a “vehicle” or agent known as a vector. The most common types of vectors used in gene therapy are viruses, which are altered to make them safe. Whilst the technology is still fairly new and some risks exist, it has been used with some success and a gene therapy product was approved for use in a regulated market for the first time in 2013.

To find out more about Gene Therapy: Youtube Video – Gene Therapy a new tool to cure human diseases Genetherapynet Website –

How does it work for Sanfilippo? For Sanfilippo, gene therapy aims at introducing a healthy copy of the defective gene into a patient to enable the correct enzyme to be produced in the patient’s own cells. A vector carrying the gene is injected via a single procedure and is spread to the patient’s cell which can then start producing the enzyme that is missing (or produced in insufficient quantities). To address the challenge of crossing the BBB, the product is either administered directly into the brain or the cerebrospinal fluid (CSF), or uses a vector that is able to cross the BBB. Gene therapy for Sanfilippo is currently at clinical trial stage.

Stem Cell Therapy

What is it?

The aim of cell therapy is to introduce new cells into a tissue in order to restore its deficient biological functions. This type of therapy uses stem cells and their self-renewing properties (stem cells reproduce identically) and their ability to differentiate into specialised cells (for example, adult bone marrow stem cells can produce all types of blood cells). The stem cells can be taken from the patient (autograft). These cells are corrected and repaired before being re-implanted (this technique combines both gene therapy and cell therapy). The stem cells can also be taken from another person who does not have the disease (allograft), but with this option, the problems of donor-receiver compatibility must be dealt with. Healthy stem cells, typically from the bone marrow, are transplanted into the individual in order to create the missing enzyme in the body. This procedure does cross the Blood Brain Barrier and, therefore, can treat mental disabilities that exist in certain lysosomal disorders. But this treatment poses problems, such as transplant rejection, along with disabling side effects.

To find out more about stem cell therapy:

Youtube Video – What are stem cells? How does it work for Sanfilippo?

Stem cells are taken from the bone marrow and specially developed so that they overproduce the missing enzyme and target the cells that traffic into the brain. The enzyme is then taken up by affected brain cells and start correcting the extra storage of heparan sulfate. Stem cell therapy for Sanfilippo is currently at pre-clinical trial stage.

Enzyme Replacement Therapy (ERT)

What is it?

ERT is a medical treatment replacing an enzyme in patients in whom that particular enzyme is deficient or absent. The replacement enzyme is referred to as a “recombinant” enzyme, produced through gene engineering. Usually this is done by giving the patient an intravenous (IV) infusion containing the enzyme. Enzyme replacement therapy does not affect the underlying genetic defect, but increases the concentration of enzyme in which the patient is deficient. ERT implies life-long treatments with regular and frequent infusions of enzyme (for example once or twice a month throughout the patient’s life).

ERT has been proven to be highly effective in some of the diseases. The safety and effectiveness of ERT for lysosomal diseases such as Gaucher disease type I, Fabry disease, MPS I (Hurler syndrome), MPS II, MPS VI and Pompe disease have been demonstrated in well-designed clinical trials, and the treatments are now commercially available throughout the world.

ERT is a very expensive form of treatment, mainly due to the complexity of the manufacturing process.

To find out more about Enzyme Replacement Therapy visit the Genzyme Website.

How does it work for Sanfilippo?

For Sanfilippo, as the enzyme is not able to cross the Blood-Brain-Barrier, ERT aims to inject the missing enzyme into the patient’s cerebrospinal fluid via a special implanted device. Enzyme Replacement Therapy for Sanfilippo is currently at clinical trial stage.

Substrate Reduction Therapy (SRT)

What is it?

The objective of SRT is to curb the synthesis or production of substrate which is not degraded and therefore accumulates. Using this method, the synthesis of a particular molecule is decreased with the aim of creating a better balance between synthesis (controlling the production of substrate) and degradation (controlling how much needs to be degraded and stored). To put it simply, produce less (but enough) to store less.

How does it work for Sanfilippo?

The objective of Substrate Reduction Therapy for Sanfilippo is to use a drug that helps the body producing less GAGs (which is the substrate) so there is less that accumulates in the cells. Several drugs have been formally trialled and whilst the trial of Miglustat concluded that it did not have a positive effect on the disease, current trials are on-going for Genistein.

Genistein is an isoflavone, a natural substance found in certain plants, and particularly soy beans and soy-based products (it is also found in legumes like chickpeas but in smaller quantities). Genistein is a product that is widely available as a diet supplement and used in a wide range of therapeutic treatments ranging from cancer to menopause, though its level of efficacy is disputed. The Genistein supplements available are in low concentration and their efficacy is very low as only a small amount of Genistein is able to cross the Blood Brain Barrier. Trials done for Sanfilippo use a specific version of Genistein that is highly concentrated.

Substrate Reduction Therapy for Sanfilippo is currently at clinical trial stage.

Palliative Treatments

Palliative care is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms. The goal is to prevent and relieve suffering and to improve quality of life for people facing serious, complex illness. This support encompasses aspects such as respite care, symptom management and bereavement support and may extend over a period of time. An assessment of medical need and a care plan can lead to support provided to the child and family so both can experience a better quality of life.

A number of therapies and approaches are used to manage the symptoms of Sanfilippo and include:

  • Speech therapy
  • Occupational Therapy
  • Physical therapy
  • Behavioural therapy
  • Diet
  • Anti-seizure medications
  • Ear, nose and throat therapies
  • Medications for heart problems
  • Educational interventions

Whilst palliative care becomes very important in the later stage of the disease, a number of strategies such as speech or occupational therapies can be put in place upon diagnostic.


Sanfilippo Children's Foundation