Patient's Voice
At the age of 3.5 years, my son was diagnosed with mucopolysaccharidosis type II (MPS II) or Hunter disease, which is a rare X‐linked genetic condition. The disease is caused by a deficiency of iduronate‐2‐sulfatase, a lysosomal enzyme that takes part in the degradation of glycosaminoglycans (GAGs). The accumulation of these compounds leads to multisystemic manifestations, such as neurocognitive degeneration, hernias, recurrent ear infections, organomegalies, skeletal deformities (dysostosis multiplex) and joint stiffness, corneal clouding, hearing loss, short stature, cardiac and pulmonary diseases with a deleterious impact in the quality of life and socialisation of the patients. Many patients die before the age of 20.
Like other genetic disorders, MPS II may manifest a vast spectrum of symptoms. The disease is clinically categorised into severe and attenuated forms accordingly to the age of disease onset, the presence of neurological involvement and length of survival. My son presented with the severe form, known by its neurodegenerative course.
Due to the nature of the disease, he had irritability, aggressive behaviour, incoordination, sleep disturbance (he used to wake up every 2 h due to agitation), difficulty in swallowing and lack of speech. Social contact was also impaired since eye contact and sustained attention were also limited.
When idursulfase (Elaprase®, Takeda Pharmaceuticals, Japan) was approved by ANVISA (the Brazilian regulatory agency for medical devices and drugs) in 2008, he started the enzyme replacement therapy (ERT), which was weekly infused. Although the drug reduces peripheral symptoms, it does not cross the blood brain barrier, thus not exerting effects on the progressive neurodegeneration. Important to mention that my son's urinary GAGs were maintained invariably on the upper limits of reference values, even on therapy.
In 2017, JCR Pharmaceuticals started the clinical trials with pabinafusp alpha (Izcargo®, JCR Pharmaceuticals, Japan) in Japan. With the goal to include Brazilian sites into pabinafusp alpha clinical development plan, I travelled to Japan with Roberto Giugliani MD, PhD (Professor of Genetics at Rio Grande do Sul University's Hospital – Brazil) to meet the JCR Team and to explain the unmet medical needs of the Brazilian patients. After that, Brazilian patients were successfully included in the phase II trial and my son started the treatment with this new molecule in 2018. The treatment is conducted by Ana Maria Martins MD, PhD (Geneticist and Professor of Genetics at Sao Paulo Federal University) since then.
No infusion‐induced reactions occurred since the treatment initiation. However, since this new drug can cross the blood brain barrier, he presented with some episodes of seizures during the first month of infusions, which were well‐controlled with anticonvulsants. Currently, urinary GAGs are at lower limits.
With the advent of this treatment, our lives were amazingly changed and now we can experience simple but precious family moments that used to be hard in our routine, such as changing clothes. In the past, this task was quite difficult due to joint stiffness and irritability, but now he assists us during all the process.
Eating is also different! In the past, we had to restrict his movements during the meals. Six months after the beginning of the treatment, he developed better coordination to use cutlery, increased the chew frequency before swallowing and the usual irritability and aggressiveness were replaced by a collaborative temper for periods of at least 1 h long, even allowing us to go to restaurants as a family. Speaking of feeding, we also realised that his taste may also have been improving since he actively demonstrates food preferences now.
Sleeping is also more resting. Awakenings are rare. He has an adapted bed, near to the floor, to avoid falls. When going to sleep, he used to recklessly jump into the bed. Now, he is able to control his movements to avoid injuries.
He learned to speak some words, he is more playful and more selective as well! He chooses the cartoons he would like to watch in the streaming platform. Appraisal and attention dramatically improved, and he has a better social interaction.
Today, after 3 years on pabinafusp alpha treatment, hugging became warmer, with higher affection, which let us indescribably happy. All of these simple but powerful daily changes may not be perfectly captured by standardised scales and clinical results, but they surely improve the lives of patients and families.
Conflict of interest: None declared.