Marco’s story is typical of a movie script. From his birth, to the tenacity of his mother, Aurora Mateos, to bring together an international group of experts to promote a new therapy against Menkes disease tested in animal models in research at the University of Texas (USA) and whose results, published in the journal “Science”, are relevant.
The Sant Joan de Déu Hospital in Barcelona, with the pediatrician and geneticist Francesc Palau in front, is carrying out this exceptional treatment, without prior clinical trial, and which has the authorization of the Spanish Agency for Medicines and Health Products (AEMPS) for a child who lives against the clock.
They have only been in therapy for four weeks, but the doctors are already seeing improvements in Marco. They do not want to throw the bells on the fly, since there is still no data to prove it, but the fact is that in this time he has managed to crawl and stand up with help, something that at his age he could not do due to severe hypotonia (muscle weakness). , among other symptoms of the disease.
“Marco did not crawl and has started to do so. This can also respond to the natural history of the child and, instead of having a regression, he is advanced ”, he comments cautiously to EFE. Dr. Palau, director of the Pediatric Institute for Rare Diseases and head of the Genetics Service at Hospital Sant Joan de Déu.
What is Menkes disease?
Menkes disease is a serious multisystemic syndrome of copper metabolism that affects 1 in 300,000 newborns in Europe, according to data from the Orphanet rare disease portal.
It is characterized by progressive systemic degeneration and connective tissue abnormalities due to poor copper distribution that does not reach the brain and other organs.
This disorder is due to the absence or alteration of the ATP7A gene, which is located on the X chromosome, and this means that women are healthy carriers, they do not develop the disease, but they can transmit it to their sons, although boys can also being born with a “novo” mutation, with no family history.
The key is not only to provide the copper that Marco’s body lacks, but also for this mineral necessary for life to cross the blood-brain barrier and reach the brain.
Until now no drug does that function. Only one, the copper histidinateis used as palliative treatment but fails to cross the brain barrier.
Marco, a child with an early diagnosis
When the coronavirus pandemic hit Aurora Mateos She was working provisionally in Rome for the United Nations and had to give birth to Marco in that city, in June 2020.
“When someone sees a Menkes child, they don’t forget it,” says the mother, who explains that they are born with curly hair and very white skin, characteristics for a first suspected diagnosis.
He was immediately transferred to the Bambino Gesù Pediatric Hospital in Rome where there is a copper unit, something unusual, and that made it easier for the child to have a diagnosis at five days of life and at the time he was injected with copper histidinate, an orphan drug.
“It seems that in the first days of birth the brain barrier is softer and it is possible that the copper could have entered. Perhaps for this reason, Marco improves his mobility, he does not have seizures, his outward appearance is so beautiful… ”, the mother tells EFE, who emphasizes that he is an “intelligent and alert” baby.
Despite early diagnosis, one of the challenges of rare diseases, Menkes disease has run its course: “It is a lethal disease, Marco has lung, bladder, neurological problems… it is a multi-system affectation,” he explains. .
When the pandemic allowed it, Marco’s family moved to live in Malaga and in the Maternal-Children’s Hospital in that city they do clinical follow-up of the child.
“Our life is medicalized, visiting the hospital at least twice a week, we cannot travel to a place where there is no center prepared to care for Marco…”, says Aurora Mateos.
The little boy is immunosuppressed, “he is a crystal child, he cannot go to daycare and you have to protect yourself with a mask to touch him… the family is afraid to come and that is hard when you need support,” laments the mother.
Special care in times of coronavirus: “He is a child who frequently goes to the emergency room and with the pandemic you don’t know how to get it right.” Sometimes the collapsed emergency has given them a scare.
“I did not sit idly by”
After the diagnosis, “I didn’t sit idly by,” says Aurora Mateos.
As a struggling mother, supported by her family, and with her experience as a consultant at the United Nations, she has managed not only to organize the association “Menkes International”but to promote a committee with twenty experts (doctors, biologists, pharmacists, lawyers…) from twelve countries that has managed the complex protocol of this exceptional treatment.
The starting point is in the study with animal models from the University of Texas, led by James Sacchettini and published in May 2020 in “Science”, in which one molecule is used, elesclomolto transport copper and cross the brain of mice with ATP7A gene deficiency.
“The results are striking, with two doses the mouse changed completely in terms of mobility, hair and survival. From only living twenty days to reaching almost 190, which in a mouse is a lot”, explains Dr. Francesc Palau, who coordinates the aforementioned scientific committee.
The scientist James Sachettini was involved from the beginning in getting this drug to Marco. The following steps were complex until elesclomol-copper was synthesized in a laboratory in India.
The Spanish Medicines Agency authorized the importation of the drug and the design of the “exceptional treatment” for Marco at the Sant Joan de Déu Hospital, with experience in previously caring for seven other patients and with an open line of research on this rare disease.
Every week, since January 31, Marco and his family travel from Malaga to Barcelona so that the little boy receives a subcutaneous dose of elesclomol-copper.
“We have started with very low doses, subtherapeutic, to gradually reach therapeutic but non-toxic ones. At the same time, we measure copper in the blood to see if we are raising elesclomol-copper and lowering histidinate”, explains Palau, also former director of the CIBER for Rare Diseases.
A clinical trial on the horizon
After a few months, data will be obtained that will determine the efficacy of this treatment in Marco and then a clinical trial will be opened that must be authorized by the regulatory agencies and whose objective will be to test the efficacy and safety of the therapy.
“I have a commitment to the Medicines Agency to design this trial. We are in contact with the North American company that owns the drug, which is interested,” says the researcher.
One of the keys is to select the candidate patients: “If it worked in Marco, it doesn’t mean that it works in all patients, we have to be careful,” says the doctor, who is already receiving calls from hospitals in other European and Latin American countries.
The hope is that this therapy pioneered by Marco can pave the way for other children with Menkes disease.
“Marco is what I love the most and we are going to fight this war until the end, no matter how many battles there are, no one is going to give up,” concludes Aurora Mateos.
