About MPS2  (Hunter Syndrome)

As a close and loving relative to Henry, I had never heard of MPS2 until hearing the devastating news that he was suffering from this rare and life-limiting disease.  I wanted to find out more, and I found a great deal of helpful information on-line.  I have no medical background or training, so what follows is just what I was able to find in the days after his diagnosis.

What is MPS2?

MPS2 is short for Mucopolysaccharidosis type II. This condition is also known as Hunter syndrome after Charles Hunter, who first described it in 1917.  For brevity, I’ll just call it MPS2 from here on.

With MPS2, the body is unable to break down some sugar molecules in the body because a very important enzyme is either missing or in very short supply.  This enzyme is called iduronate-2-sulfatase (I2S).  As sugar molecules build up in organs and tissues, they cause damage that will affect Henry’s physical abilities and his mental development.

Thankfully MPS2 is a very rare disease with less than 1 in 100,000 children being diagnosed with it.

MPS2 is a genetic disease that almost always only affects boys.  This is because it is passed from parent to child through the ‘X’ Chromosome.  Girls inherit two ‘X’ chromosomes from their parents, while boys only inherit the one, so the chance of a girl inheriting two of the faulty ‘X’ chromosomes is extremely remote.  However, if a female inherits one faulty ‘X’ Chromosome she can become a carrier.

The signs and symptoms of MPS2 typically start to appear between 2 and 4 years old.  In Henry’s case we had some concerns that he seemed to be late walking and in starting to talk.  In April 2021 he was admitted to A&E with severe vomiting and while he was there, other abnormalities were found.  He was eventually transferred to Great Ormond Street children’s Hospital (GOSH) for further investigation.

It was 4 months after his second birthday that Henry’s MPS2 diagnosis was confirmed.  The severity of MPS2 depends on how much enzyme the body is able to produce.  In the most severe cases, the body is not able to produce any of this vital enzyme.  Sadly, Henry was diagnosed with this most severe case.

Severe MPS2 is life threatening, with life expectancy typically between 10 and 20 years.  How and where the sugars build up in the body and what damage they do varies on a case-by-case basis.  For this reason, we cannot know exactly how MPS2 will progress in Henry.  In many cases the problems seem to get a lot worse between the ages of 6 to 8.  These problems can include breathing problems, heart disease, joint and bone problems, hernias, and seizures.   Right now, Henry is bigger than the average 3-year-old but, by the time he reaches 5-years-old, this will reverse, and he will not grow so fast as other children.  Physical and mental development will be impacted in a number of ways.

So, the bad news is that without treatment or a cure, Henry will have a short life that will be full of illness and problems, most likely punctuated by hospital stays and various operations and treatments.

The Treatment

Currently there is no cure for MPS2, but the symptoms can be treated, and the worst effects delayed.  The most effective treatment is Enzyme Replacement Therapy (ERT), and Henry has been receiving this for the past year.  The replacement enzyme is called Idursulfase, and in Henry’s case, this must be supplied every week.  Each treatment takes about three hours, during which time the Idursulfase must be absorbed into Henry’s blood stream.  Initially this treatment was undertaken on-site at Great Ormond Street Hospital (GOSH), but now it is done at home.  Here’s how it works:

• The day before the treatment is due, the drugs are delivered.  Idursulfase is very expensive, and great care is taken not to waste any.
• The next day a specially trained Nurse arrives to give the treatment. Henry has a ‘port’ built in under his skin on his chest.  Before the nurse arrives, a numbing cream is applied to the area around the port, and some medication is given to prevent adverse reaction to the treatment.
• The toughest part is connecting a needle and tube into the port.  Henry is a strong little guy, and it typically takes three of us to hold him down (and keep him absolutely still) to get this done.
• With the tube in place, Henry must remain connected to the drug supply for about three hours, along with an electronic device that monitors the progress of his treatment.  This is all placed into a neat little backpack that Henry wears for the three-hour duration.  He is quite used to this, and after the initial upset of being held down and ‘plugged in’ he then just carries on as he normally would – playing and getting up to mischief.

As a regular ‘holder-downer’, I cannot speak highly enough of the nurse visitors who administer the treatment.  They stay close to Henry throughout the treatment period, making regular checks.  The way they relate to Henry is really lovely to see.  You’d have thought that by now Henry would associate their arrival with an unpleasant experience.  But he usually greets them with a big hug and always wants them to play with him.

No matter how effective the ERT, it can only ever be a delaying tactic.  Sooner or later the effects of MPS2 will start to accumulate and cause damage despite the treatment.  This is why we need a cure.

The Search for a cure

There are various research projects going on as well as trial treatments.  Henry narrowly missed getting onto a clinical trial in Pittsburgh USA in 2021.  This was disappointing, but there will be other trials and ultimately a cure.   Please watch this space for information about new developments and potential cures.  The good news is that a number of studies are currently underway.

For Henry, time is of the essence.  He needs a cure before the worst effects of MPS2 have the chance to inflict too much irreversible damage on him.

Promising Research

There are various research projects going on around the World including the following:

RGX-121 Gene Therapy is designed to deliver a functional copy of the defective gene (iduronate-2-sulfatase) to the central nervous system.  A clinical trial is ongoing in the USA to determine the effectiveness and safety of this treatment.  This is the trial that Henry narrowly missed due to not meeting all the criteria – other patients were more suitable.

DNL310 Enzyme Replacement Treatment is potentially more effective than Henry’s current ERT treatment because it can directly impact the central nervous system (Henry’s current ERT is unable to cross the blood-brain barrier).    This particular trial is only available to older children (from 5 to 10) so Henry is too young to take part.

GNR-055 Gene Therapy is designed to deliver a modified version of the defective gene which is capable of crossing the blood-brain barrier.  While not a full cure, this research should deliver a significant improvement  in life expectancy and quality of life.  Unfortunately, the clinical trial sites are all in Russia, so this is not a practical option for Henry right now.

JR-141 Gene Therapy is a another treatment that is able to across the blood-brain barrier using a proprietary technology called J-Brain Cargo.  JCR is a Japanese pharmaceutical company that has already had their technology approved in Japan and it has already seen significant improvements in Japan for MPS2 sufferers.  We are hoping that this technology can shortly be approved and made available in the UK.     

One common theme in the above is mention of the blood-brain barrier.  This is important, because Henry’s current ERT treatment cannot pass through this barrier.  So while his current ERT will work against the build up of dangerous sugars in his body, it cannot prevent them building up in his brain and central nervous system – and this is exactly where a great deal of harm can take place.

I’ll be adding to the list above as I discover more.  GOSH is fully aware of all the relevant research and can be relied upon to apply for suitable trials and treatments on Henry’s behalf.

 

UPDATE: June 2023

Ater a number of false starts and following an agonising wait, Henry has now been accepted onto a trail.  This is the 3rd trial of the RGX-121 Gene Therapy mentioned above.  On June 17th Henry flys out to Oakland Califonin with Mummy and Daddy for up to 12 months.  This is fantastic news and what we have been waiting for so long.  We won’t be posting any details of the trial itself, but there will be regular updates on Henry’s adventures in the USA