Like the disease Elephant Man suffers from, Cloves syndrome is a closely related genetic defect that results in accelerated deformities of organs and limbs. French researchers have tested a specific inhibitor against the gene responsible for this rare disease: PIK3CA. Tried on 19 patients, the inhibitor is also developed in blood diseases, and has demonstrated spectacular effects.
It is a disease as rare as it is impressive: Cloves syndrome, an acronym for “congenital lipomatous growth, vascular malformations and epidermal nevi”. This condition, similar to that suffered by Elephant Man, deforms organs and entire parts of the body with monstrous growths. Until now incurable, Cloves syndrome affects 50 people worldwide and develops in more or less serious forms depending on the patient. All now have a hope of recovery.
In an article published on June 13 in the scientific journal Nature, French researchers claim to have developed a treatment: one tablet per day containing a single molecule, currently developed for blood diseases, would indeed be effective against the disease and its symptoms with very significant regressions of deformities.
The mutation in the PIK3CA gene that causes the disease
Among the symptoms affecting people with Cloves syndrome, fatty tissue growths, manifestations affecting the skeleton such as a major enlargement of the bones, deformations of organs such as the brain or kidneys, vascular malformations or even scoliosis.
Called “patient 1” of the study conducted by Inserm researchers, Emmanuel (pictured), a 29-year-old aeronautical engineer, suffered from an enlarged left leg, scoliosis and vessel malformations. who, by damaging his spinal cord, had left him paraplegic.
Lessons for cancer drug treatment from tackling a non-cancerous overgrowth syndromehttps://t.co/cptTg7oz8T https://t.co/cptTg7oz8T
– CLOVES Syndrome (@CLOVESSyndrome) June 14, 2018
He is the first patient to have benefited from the experimental treatment, which itself stems from a very recent discovery made by American geneticists. It was not until 2012 that the latter discovered the PIK3CA gene, the mutation of which is at the origin of Cloves syndrome. The PIK3CA gene regulates the proliferation and growth of cells. When over-activated, it causes excess growth in the parts of the body affected by the mutation.
Researcher at Inserm and at the University of Paris-Descartes, Guillaume Canaud then set out in search of a treatment. “I was thinking that there may already be a drug capable of blocking the effects of the PIK3CA mutation”, explains the nephrologist, who has tested several molecules.
A single tablet to take every day
Among the “specific inhibitors” of the tested gene, BYL719 from the Swiss laboratory Novartis and developed in blood cancers, appeared particularly promising. In 2015, the French Medicines Agency (ANSM) exceptionally authorized the medicine to be used to treat Emmanuel at Necker hospital “.
“Very quickly, we saw that it worked,” explains Dr Canaud. Emmanuel “told us what all the other patients told us: that he felt a lot less pain, that something was happening”. The photos taken by the doctor attest to this: the vascular masses and the growths clearly decreased after taking the treatment.
The downside is that this medicine is not curative. It is suspensive and must be taken every day to block the hyperfunction of the PIK3CA gene. But, today, 19 patients, the youngest of which is 4 years old, take the treatment daily: a single tablet (250 mg per day for an adult) to be taken in the morning and which, for the moment, does not present no noticeable side effect.
Syndrome #CLOVES & hypergrowth syndromes: remarkable improvement in the state of health of 19 patients thanks to a new therapeutic strategy https://t.co/2iGQ5uxAhS
A model of successful work between researchers @Inserm and @UParisDescartes and doctors @APHP pic.twitter.com/A7TVYqbmp6– Inserm (@Inserm) June 13, 2018
For Dr Canaud, “this treatment will radically change the fate of patients with hypergrowth syndromes associated with a PIK3CA mutation. The drug has made it possible to obtain results exceeding our expectations with regressions of malformations, which have been present for many years, but also an improvement in the quality of life of patients and those around them. BYL719 thus represents tremendous therapeutic hope even for very severe forms. “
According to the doctor, it is estimated that a thousand patients with Cloves syndrome in France, but they are “surely more than that in reality, because there is an underdiagnosis”. The Necker hospital is also expecting an influx of patients demanding the same treatment. A form will soon be available online for patients who wish to join the experimental protocol.
Good news: New treatment improves condition of patients with Cloves Syndrome https://t.co/cii1Z9EGaX via @Youtube
– Emer O’Siochru (@eosfuturedesign) June 15, 2018
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