A year ago Marco Mateos began an exceptional and pioneering treatment in the world against the ultra-rare genetic disease of Menkes. The improvement shown today by this child, who lived against the clock and is now taking his first steps, opens the door for other affected children.
Marco, 32 months old, with exceptional treatment against the rare Menkes disease, with his mother outside the Hospital Sant Joan de Déu in Barcelona. EFE/ Andreu Dalmau
The launch of an upcoming clinical trial, the possibility of creating an international reference unit in Menkes disease at the Hospital Sant Joan de Déu in Barcelona, where the treatment is developed, and that another baby, in Léó, being the second child in the world with this therapy are some of the fruits left by Marc’s case.
On the eve of World Rare Disease Day, we explain the case of this 32-month-old boy, who suffered from severe hypotonia (lack of muscle tone and strength) and who is now able to crawl, to walk with the help of walker and get up off the floor with his own effort, in addition to speaking in small sentences and with a completely normal level of understanding.
Motor and cognitive functions that a year ago he was barely developing due to this multisystem disorder of metabolism generated by the alteration of the ATP7A gene that causes copper, an essential mineral for life and which we obtain from food, it is not distributed and metabolized correctly by the different organs, including the brain.
“Marco’s evolution is being very good, it’s not that he has recovered all functions but many”, he explains to EFE in Barcelona doctor Francesc Palau, director of the Pediatric Institute of Rare Diseases and head of the Genetic Medicine Service at Hospital Sant Joan de Déu.
It is necessary that until the clinical trial is developed that tests the safety and effectiveness of this exceptional treatment with more patients, Marc’s improvement cannot be scientifically confirmed.
“But the boy is making good progress and, therefore, we think that it may be the molecule that is changing the natural course of his disease,” he says.
Marc’s cognitive level
Marco’s mother, Aurora Mateos, lives every day the evolution of a child who had a short life expectancy: “The neurologists are left with their mouths open, the neurocognitive development is absolutely normal, even a little higher “.
The child understands and responds, in his own way, to Spanish, his mother tongue; the Russian, the father, and the English he listens to at home. “It’s incredible that a child with Menkes disease reaches this level”, says the mother.
But this disorder has indeed left some marks on Marco, such as pulmonary fibrosis that last January I took him to the hospital in a critical situation and the need to carry, sometimes, a nasogastric tube to ensure his food. The Maternal and Child Hospital of Málaga, where the family lives, does the general follow-up.
A mother’s initiative to get a unique treatment
Aurora Mateos, appointed as a consultant for the United Nations, is the one who has promoted, through the Menkes International Associationthis unique experimental treatment whose protocol and supervision is managed, disinterestedly, by the Copperless Committee made up of twenty experts (doctors, biologists, pharmacometricians, lawyers…) from twelve countries coordinated by Dr. Palau.
The starting point is the study with animal models from Texas A&M University (United States), led by James Sacchettini and Vishal Gohil published in May 2020 in “Science”, where a molecule is used, elesclomolto transport copper and cross the blood-brain barrier of mice with mutation of the gene homologous to ATP7A.
The radical change experienced by these mice, both in mobility and survival, set in motion arduous efforts to synthesize sclomol-copper and for it to be approved as an experimental treatment at Sant Joan de Déu.
Marco receives a weekly subcutaneous injection of a tiny amount of sclomol-copper and continues daily with copper histidine, a palliative treatment he has been given since he was diagnosed with Menkes disease on the fifth day of life, which which may also be playing in his favor as he has never suffered from the usual epileptic seizures.
So far, the child has not had any episode of cooking poisoning, just some insignificant skin reaction. How long he will be able to receive this therapy is still unknown.
“Copper, in small amounts, is necessary for life but it is also toxic and therefore we cannot always be supplying copper externally”, warns Dr. Francesc Palau who points to new avenues of research such as therapy gene
The other “frames”
With only four months to live, Reda has become the second child to be treated with sclomol-copper after being prenatally diagnosed with Menkes disease.
Reda was born prematurely with her twin, Rayan, also with the disorder and who could not overcome bronchiolitis shortly after birth. Prenatal diagnosis was possible due to the antecedents, the older brother died at 3 years of age.
At the University Hospital of León, this baby benefits from exceptional treatment with permission from the Spanish Medicines Agency; the collaboration with Hospital Sant Joan de Déu and the management of the Menkes Internacional association.
The neuropediatrician Aquilina Jiménez assures EFE that in a month and a half of treatment, she has observed how Reda already fixes her gaze and smiles and is confident in the good results of having started the therapy early.
Like Reda and Marco, other “menkes” children from Spain and the rest of the world could be candidates for this treatment.
A clinical trial in the plains
The pharmaceutical company Engrail, owner of the molecule, is conducting preclinical toxicity tests in animal models to receive authorization from the regulatory agencies, American and European, and to select suitable patients.
“Hospital Sant Joan de Déu has positioned itself as a candidate to coordinate this clinical trial,” explains Dr. Palau, with the possibility of creating an International Menkes Disease Reference Unit in this center that would cover the clinical trial.
This hospital, a leader in rare diseases, has received more than fifty calls and contacts from patients and doctors from all over the world interested in this pioneering therapy in Menkes after learning about Marco’s case.
“Marco is a hero and thanks to him and the experts who have accompanied us we have achieved all these results in one year”, says Aurora Mateos who warns that there is no time to lose to give hope to other children with Menkes disease.