Therapeutic Avenues Being Investigated

These are some of the most-promising therapeutic avenues being investigated by researchers and organizations/institutions around the world to find a treatment or cure for Sanfilippo Syndrome.

Enzyme-Replacement Therapy

What Is It?

Enzyme Replacement Therapy (ERT) is when a patient is given an infusion of the enzyme their body lacks. There are different modes of administering ERT (IV, intracranial, etc.), all seeking the best circulation of the enzyme throughout the body, especially in reaching the brain, which a highly-compartmentalized and protected organ.

ERT is administered as a routine infusion in a hospital setting.

How could it help in Sanfilippo Syndrome?

The fundamental cause of Sanfilippo Syndrome is a child’s inability to create a single enzyme in the body’s process of breaking down heparan sulfate, a natural cellular waste.

Like diabetics taking insulin to supplement their body’s lack, ERT provides a child’s body with the missing enzyme in the process of breaking down heparan sulfate. With the replacement enzyme, the child’s body now has the missing element for breaking down that natural cellular waste.

Gene Therapy

What Is It?

Gene therapy provides a patient with a functioning gene for the defect in their body. The functioning gene takes over for the mutated gene, restoring normal cellular function.

Read about the ethical issues in pediatric gene therapy clinical trials.

How could it help in Sanfilippo Syndrome?

Gene therapy for Sanfilippo provides the child with a functioning gene, so their body begins breaking down heparan sulfate. A virus is used to deliver the functioning gene and spread it to cells throughout the patient’s body.

Substrate-Reduction Therapy

What Is It?

If a body can’t break something down, what if there’s less of it in the first place? Substrate-Reduction Therapy (SRT) seeks to inhibit a body’s production of materials (“substrate”) so there’s less build up of the materials it can’t break down.

How could it help in Sanfilippo Syndrome?

A child with Sanfilippo Syndrome creates heparan sulfate that their bodies can’t break down as needed. But what if their bodies produced less of it in the first place? This therapy aims to slow the progression of Sanfilippo because the children’s bodies would produce less of the cellular waste that damages their bodies in the first place.

Stem-Cell Therapy

What is it?

A stem cell is the body’s raw material. The Swiss Army Knife of cells. It can “differentiate” itself and become a specialized cell that the body needs, like a blood cell, muscle cell, or neural cell, or it can divide and create additional morphable stem cells.

Leveraging both abilities of a stem cell (differentiation and regeneration) are options for treating diseases.

How could it help in Sanfilippo Syndrome?

To treat Sanfilippo Syndrome, gene-modified stem cells could be used to over-express (over produce) the enzyme that a child with Sanfilippo is missing, restoring the cellular function of clearing the body of heparan sulfate.

Additionally, stem cell therapy could help regenerate the damaged central nervous system and prevent or reverse immune activation.

Autophagy Therapy

What is it?

Autophagy is a process by which cells engulf and dispose of misfolded proteins and damaged mitochondria that occur during normal metabolism and even more so in disease states.

The therapy would activate autophagy in the brains directly or by inhibiting Tor, a master regulator and suppressor of autophagy. mTOR is a universal pathway that is not disease specific, so success with activating autophagy would translate across MPS conditions and neurodegenerative disorders.

This pathway is being studied through genetic modification and the use of an FDA-approved class of drugs known to block mTOR activity that is currently used to treat children with tuberous sclerosis complex and has been shown to reduce seizure frequency and severity.

How could it help in Sanfilippo Syndrome?

Research has shown that in neurodegenerative diseases, such as Sanfilippo Syndrome, there is an impairment in the body’s ability to carry out the autophagy process. This causes other parts of the cell to function poorly and eventually leads to cell death.

Stimulating autophagy could positively impact the neurodegenerative process in Sanfilippo Syndrome, beyond replacing the primary enzyme deficiency. Developing complementary strategies, such as this, to improve the life of children with this devastating disease is a critical need.

Research Underway

See which of these therapeutic avenues are currently under investigation.