Researchers around the world are working to develop effective treatments for children with Sanfilippo and the approaches can be divided into four categories described below. There are several promising clinical trials underway and these have been summarised in our Sanfilippo clinical trial factsheets for each subtype.


Gene therapy and genome editing

Involves introducing a gene into the body which contains the instructions to make the enzyme that is missing in Sanfilippo. Usually, a harmless virus is used to deliver the gene – a commonly used virus is the adeno-associated virus (AAV). Gene therapy is a single procedure, with the therapy injected either directly into the brain, into the cerebrospinal fluid (CSF) or into the bloodstream. There are several clinical trials of this approach underway, read about gene therapy clinical trials here.

An emerging approach is genome editing which may be able to correct the genetic mistake. It is also sometimes called “CRISPR”. This research is in the early stages.


Enzyme Replacement Therapy (ERT)

Involves replacing the enzyme that is missing in Sanfilippo with enzyme produced in a laboratory. This therapy involves regular injections of the enzyme either into the bloodstream or directly into the brain. Getting enough enzyme into the brain has proven to be a challenge, and several clinical trials of this approach have failed, but other clinical trials are continuing using different technology. Read about the ERT clinical trials here.


Stem cell therapy

Stem cells have the unique ability to develop into the many specialised cell types of the body, such as muscle cells, blood cells or brain cells. They can also multiply so that their supply doesn't run out. They are essential for growth and repair of the body. Stem cell therapy can involve taking stem cells from a donor (as happens with a bone marrow transplant) or correcting the genetic mistake in the patient’s own stem cells and reintroducing them to the body.
An appealing advantage of stem cell therapy is that it may be able to reverse the damage that has occurred in the brains of children with Sanfilippo. Research into stem cell therapy for Sanfilippo is still in the early stages, and there is no proven therapy available.

A clinical trial of a stem cell-based gene therapy is being planned by Orchard Therapeutics – read more here.


Other targets 

Researchers are working to find other drugs that may reduce the progression of Sanfilippo and improve quality of life; these include:

  • Substrate reduction therapies to reduce the amount of heparin sulphate that is produced by the body so that there is less to build up
  • Chaperones that help the faulty enzymes fold correctly and do their job of breaking down heparan sulphate
  • Drugs that increase a process called “autophagy” that clears unnecessary or dysfunctional components from cells, allowing them to function better
  • Drugs to target certain parts of the immune system that are thought to contribute to the cognitive decline seen in children with Sanfilippo
  • Researchers are testing large libraries of drugs with many different modes of action on cell models of Sanfilippo to see if any can be repurposed for Sanfilippo with the hope of alleviating symptoms. For example, read about our ‘Brain in a Dish’ project 
  • Treatments targeting the symptoms of the disease such as behavioural problems, sleeping issues or lung function, which aim to improve the quality of life of children with Sanfilippo and their families.

There are two trials in this category, either started or being planned:

Anakinra - a drug that suppresses inflammation is in clinical trial at the Lundquist Institute (formerly LA Biomed) in the USA. Cure Sanfilippo Foundation is a collaborator on this trial. This drug is approved for the treatment of rheumatoid arthritis (RA). More information about this trial:

A clinical trial of Trehalose - a small sugar, is being planned by Seelos Therapeutics and Team Sanfilippo in the USA. Trehalose is to be given intravenously (through the vein). It is hoped that the trehalose will enter the central nervous system (the brain and spinal cord), stabilise proteins, and promote autophagy, a process to dispose of aggregated proteins and other cellular waste.


More information