Paloma Oliveto Special Envoy*
posted on 09/04/2022 06:00
(credit: Personal archive/Reproduction)
Santiago (Chile) — Chronic pain, depression and difficulties in performing simple tasks, such as personal hygiene, are part of the reality of patients with a genetic syndrome responsible for most cases of dwarfism in the world. This popular term, which has been replaced by the expression skeletal dysplasia, refers to diseases in which there is a change in the shape, size and constitution of bones and cartilage. The visible consequence is short stature. However, the problems that these conditions cause go far beyond physical appearance.
An unprecedented study in Latin America on the quality of life of people with achondroplasia, a rare skeletal dysplasia that affects around 250,000 worldwide, shows the challenges in the lives of children, adolescents and adults living with a disease for which there was no treatment. until recently (read more below). Conducted with 172 patients from Brazil, Argentina and Colombia, the Lifetime Impact Study for Achondroplasia (Lisa) research shows, among other data, that 53% of patients between 8 and 17 years old suffer from pain in at least one part of the body.
In addition, nearly 27% of adults reported moderate to severe depression or anxiety—in the general population, that figure is 4%, according to the World Health Organization (WHO). For 17.8% of them, simple activities such as turning on and off a faucet, standing for long periods and calling the elevator are difficult or impossible to perform without the help of other people or adaptation equipment.
“I’ve been a geneticist for many years, but I confess that I was very naive about achondroplasia. I had no idea how sick these people are,” said Dr Juan Llerena Júnior at the presentation of the study in Santiago. The specialist from the Medical Genetics Center of the Fernandes Figueira Institute of the Oswaldo Cruz Foundation (Fiocruz) was one of the leaders of the survey, which had the participation of 94 Brazilian patients, equivalent to 54.6% of the total.
“It’s not just dwarfism, but potentially serious neurological conditions, such as hydrocephalus and spinal cord compression,” explained Wagner Baratela, a geneticist at the Santa Casa de Misericórdia de São Paulo and himself a patient with another type of skeletal dysplasia. . The specialist, who is a member of the Brazilian Society of Medical Genetics, also participated in the presentation of Lisa.
Achondroplasia is one of 700 genetic disorders that affect skeletal development, and although it is hereditary, 80% of cases result from so-called de novo mutations, when neither the father nor the mother carry the variant. For some unknown reason, patients have a defect in the FGFR3 gene, which is associated with growth.
In people without the disease, this gene slows down bone development, preventing the child from overgrowing. However, in patients, FGFR3 is permanently activated, causing growth velocity to be affected. The result is short stature, in addition to a series of complications that accompany the individual from childhood to adulthood. Among them, increased intracranial venous pressure, respiratory problems such as apnea, obesity and dental complications.
Until the recent approval of the vosoritide molecule by the European Medicines Agency, the Food and Drug Administration (USA) and, finally, in November last year, by the National Health Surveillance Agency (Anvisa), the only treatments were palliative, indicated for associated comorbidities. Among them, painful interventions, such as bone stretching, and delicate, such as spinal decompression.
The substance, from the BioMarin laboratory, was approved by regulatory agencies due to the results of research that attested to its efficacy and safety. The phase 3 clinical trial, published in The Lancet, involved 121 children aged 5 to 14.9 years. The initial mean annual growth (ACV) was 4.26 cm/year, against 4.06 cm/year in the placebo group. At the end of the study, after 52 weeks, the participants who took vosoritide grew 1.57 cm/year more than the others.
Upon completion of the study, 58 randomly chosen participants were enrolled in an extension study for two years. In the period, the increase in VCA was maintained, according to an article published in the journal Nature Genetics. The molecule works as an analogue to a peptide that exists naturally in the body, CNP. It inhibits the action of some enzymes that hinder bone growth, thus stimulating growth.
The problem is the high cost of the drug, which has to be taken daily until puberty, when, naturally, the child stops growing. The price in Brazil, defined by the Medicines Market Regulation Chamber, exceeds R$ 2 million annually, including import costs.
To fulfill her dream of seeing her son Isaac, 4 years and 6 months old, develop with a better quality of life, lawyer Karina Falchi, resident of Campo Grande (MS) went to court. On August 30, the boy took the first subcutaneous dose of the drug. Six months passed between the favorable decision and the start of treatment. “We are overjoyed, living a miracle. The concern we have is with the quality of life. The life expectancy of an adult with dwarfism is 10 years less than that of a typical person, and that is a life full of surgeries and complications. my son is spared this, it will be wonderful. The growth is a bonus”, he says.
The diagnosis of achondroplasia was closed when Isaac was 5 months old, but from the 30th week of pregnancy, Karina knew that her son had some growth disorder. With recurrent ear infections and an adenoid that resulted in sleep apnea, the child needed surgery, which corrected the second problem, although the first continues. Since 2018, following news about the development of vosoritide, Karina says that when Anvisa approved the drug, commercially called voxzogo, she felt a mixture of happiness and concern. “Can you imagine knowing that the medicine exists, but you don’t have access to it? For the other families, I leave the message that they have hope, because it is possible”, she says.
The reporter traveled at the invitation of the BioMarin laboratory
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