Researchers, parents and patients meet in Marseille

On Jan 16, the Italian and French research groups that work on Laminopathies met in Marseille. It was a combined meeting for doctors and patients, including parents of children with progeria. ‘Laminopathies’ include all diseases that are caused by a non-functioning Lamin A/C gene, and progeria is one of these.

The meeting was spread over two days: lectures of the first day were meant for physicians and researchers. The second day was also intended for the patients. Some of the lectures second day went very far in the theory and were not easy to follow for families, other presentations were addressed to them.

The main lecture for families with children with progeria was presented by Dr. Annachiara De Sandre-Giovannoli, from the lab of Dr. Nicolas Levy. She first gave an overview of all therapies that have been given in the past, and their results. Next she discussed the new substances that have been developed and in part also already tested in mice with progeria. These substances all focus on the principle to change the RNA from which Lamin A/C is made. The simple summary is that DNA makes RNA, and then RNA makes proteins. Since children with progeria have abnormal DNA, they form abnormal RNA, which leads to a different lamin A/C and an ill-structured Lamina in their cells. If the deviation in the RNA can be corrected, this will not only repair the abnormal Lamin A/C, but will also produce normal functioning Lamin A/C.
There are now a number of substances that can correct this RNA. These substances work well in mice. In mice they show no important side effects. The presented results were really good. The main problem is to ensure that the substances end up in the right quantity at the right place in the body, without the body breaking the substances down. The lab has contacted the company Sarepta, a pharmaceutical company that has a lot of experience with this type of medication (they use them also for the muscle disease Duchenne muscular dystrophy). Researchers and Sarepta work together to find a cure.

Dr. De Sandre-Giovannoli explained what steps should all be taken before one can start with a trial. These are mainly administrative procedures, which usually require many years with an ordinary drug, but because they always ask for extra rush everywhere, they should be able to succeed in about a year. That means that if all goes well, this one trial could start sometime in Spring 2016.

What can the families do in the meantime?

1. For all children the use of statins is and remains useful. Statins can be given by the General Practitioner or paediatrician.

2. Whether it makes sense to use also other medication is very uncertain. The Boston group has offered a trial with Lonafarnib. A small percentage of the children showed some improvement in weight gain and formation of bone and blood vessels. The result were really limited, but there were some results. The Boston group stopped their trial, but still provide Lonafarnib to children with progeria. Children can come to Boston for a complete check-up, and will receive sufficient Lonafarnib for two years, without further checks/travels to Boston. Each family has to decide whether adding Lonafarnib is worthwhile, balancing the burden of travelling and the exams in Boston, plus the subsequent daily taking the medication thereafter, and the limited results that it can potentially offer. There is no general rule here, each family will have to make their own decision in this. The alternative is to use no other drug next to statins, and await the upcoming trial in Marseille. We have currently no new information from Boston and do not know whether there are plans for a new trial as well.

The above gives us in fact mixed feelings: the good news is that important new substances have been developed and even already tested, and these are really promising. The downside is that it all takes longer than we had hoped for. A new trial somewhere early next year, and till that time very limited possibilities (next to statins).

Raoul Hennekam

The program of the meeting in Marseille can be found HERE.

Life According To Sam

Happy Holidays!

the beneficial effect of antioxidants in broccoli

The extreme aging in Progeria is caused by an accumulation of a fatty protein that is called Progerin. The presence of Progerin blocks a number of functions in the cell nucleus. This poor protein, which normally would be disposed of in large part, can not be degraded because a genetic code is missing. The clean-up system in the cell is not functioning due to a mutation in the LMNA gene.

The accumulation of Progerin affects several cellular functions. It is also found in healthy cells, but to a much lesser extent. In children with Progeria ten to twenty times more Progerin has been found in the nucleus.
These patients can only make an incomplete form of the protein lamin A. Healthy lamin A has an important function in the wall of the nucleus, it protects the DNA in the cell and plays a role in gene expression. Progerin, a byproduct, only has a function in the construction phase of the protein; it should be disposed of once the nucleus has been formed. However, when it accumulates in the nucleus, progerin causes problems. Patients with progeria develop many problems, including atherosclerosis and osteoporosis, they run the risk of an early stroke or heart attack.

Researchers from the Technical University of Munich (TUM) found more than 28 proteins with a wide range of functions that were not effective in the nuclei of HGPS patients - all the result of the mutation in the lamin A gene. However, they have also shown that the level of progerin in diseased cells can be lowered, by reactivation of the 'cleaning' process. They found a beneficial effect of the antioxidant sulforaphane, found in broccoli (especially in young broccoli sprouts) and other cruciferous vegetables such as cabbage and Brussels sprouts. Sulforaphane (1-isothiocyanato-4-methylsulfinylbutane), showed to reduce the accumulation of Progerin. The progeria cells they treated with sulforaphane also showed decreased DNA damage and less deformation of the nucleus.

source: Sulforaphane enhances progerin clearance in Hutchinson–Gilford progeria fibroblastst, Diana Gabriel, et al., Aging Cell - Doi:10.1111/acel.12300

Spanish study may lead to better therapies for cancer and progeria

Premature aging diseases provide ‘models’ through which many hope to gain insight into the human aging mechanism. They provide an effective model for analyzing the body’s maturation process. The observation in mice of the effects of Prelamin A, the protein that causes progeria, has shed some light in the complex connection taking place between the ageing processes and cancer, since these are closely related. Several years of collaboration between the Institute of Molecular and Oncological Medicine of Asturias (Imoma) and the University of Oviedo has lead to new findings. The spanish scientists discovered that the protein Prelamin A, that speeds up ageing, may slow cancer.

In order to carry out their research, the Spanish scientists have used mosaic mice, genetically modified, to keep 50% of cells with Prelamin A in their tissues during their whole life. The study showed that the Prelamin A causes progeria through cell-extrinsic mechanisms, but also prevents cancer. Suprisingly, these mosaic mice are completely healthy and do not show progeria in spite of having the ageing protein in half of their cells. They live as long as normal mice. This suggests that in order to treat fast ageing it would not only be necessary to fix defects from the affected patient’s cells.

The study made two important discoveries. Firstly that the mosaics are totally healthy, showing none of the alterations that the mice with progeria caused by prelamin A have. Secondly, although the mosaics develop the same number of tumours as normal mice, they have far fewer malignant tumours (those capable of breaking down the barriers that confine them and invading the surrounding tissue).

Carlos López-Otín, one of the researchers, remarked that the achieved results are very encouraging from the scientific point of view, although the development and application of therapies need to be carefully stated. 

José María Pérez Freije, of the University of Oviedo, noted that 'these results invite hope for treating patients with rapid ageing, as they suggest that it is not necessary to correct defects in all cells, but probably only in some of them'. Rubén Cabanillas, of IMOMA said: 'by inducing prelamina A production in cells obtained from human malignant tumours, we observed that their invasive capacity is drastically reduced'.

The finding that the protein that causes fast ageing, Prelamin A, is capable of halting the advancement of malignant tumors, may allow the development and application of new therapies to fight cancer as well as progeria.

special... with good reason

In this documentary three members of the progeria family circle 'dreamteam' explain why they help to bring the progeria children and their families together.

new approach for progeria treatment with inhibitor for ICMT

Researchers at Sahlgrenska Academy, the University of Gothenburg, Sweden, have published new results of their work in Science. The group investigated the progeria mutation, that occurs in the protein prelamin A and causes it to accumulate in an inappropriate form in the membrane surrounding the nucleus.

The target enzyme of this study is called ICMT, it attaches a small chemical group to one end of prelamin A. In progeria, blocking this attachment could possibly reduce the development of premature ageing symptoms more effectively. The publication in Science is based on in vitro studies on cells, and has been tested in vivo on mice, treated with a common inhibitor of ICMT. The impact of inhibiting ICMT will need further testing on progeria mouse models with more specified candidate ICMT inhibitor drugs -developped by a collaborating group in Singapore- before it can be offered in a trial to patients.

ICMT has also become the focus of research in the quest for discovering new and more effective cancer therapies. The article Targeting Isoprenylcysteine Methylation Improves Disease Phenotypes in a Mouse Model of Accelerated Aging has been published on May 16. Further reading at Science and the University of Gothenburg.

Unique molecular mechanism protects neurons in progeria patients

Progeria is an extremely rare genetic disease, which induces premature and accelerated ageing in patients. The mutation causing the syndrome affects the LMNA gene that encodes proteins called “lamins” A and C.

Lamins are involved in maintaining the structure of the nuclear membrane. They determine nuclear shape and stiffness and allow communications within the cells. In the case of progeria, lamin A is defective. In its mutated form, it becomes toxic and damages the membranes of the nucleus, disrupts the message and causes accelerated ageing of cells. In 2003 the research team of Dr. Nicolas Levy in Marseille identified the origin of this disease.

The development of this syndrome is rapid: it is estimated that each year, affected children age by more than ten years, leading to their premature death between 13 and 16 years. This accelerated ageing affects most tissues: skin, blood vessels, heart, bones or muscles. Very quickly, patients suffer from muscular and skeletal disorders, stunted growth (their size does not exceed 110 cm for a weight of 15 kg). In contrast, their cognitive abilities are usually not affected. This has always been considered a surprising phenomenon, given the overall disease involvement to which these patients are subjected.

One of the studies of Xavier Nissan et al. in their progeria project showed a unique molecular mechanism that specifically protects neurons in patients with Hutchinson-Gilford progeria syndrome from the defective prelamin A processing.

Skin cells sampled from patients with progeria were induced into pluripotency then differentiated into mature nerve cells. Tuj1 markers highlight nerve cells in green; other markers highlight DNA in blue. Lamin A, if present, would appear in red; the protein is however completely absent in this cell view. 

Copyright: Xavier Nissan, I-Stem 

You can download the extended PDF file of this publication HERE.

The strategy at I-Stem

Recently two phase II clinical trials were initiated by treating HGPS patients with Farnesyltransferase inhibitors (FTIs) and/or the combination of Zoledronate and Pravastatin to prevent or delay the gravest infringements of the disease. Although these two studies have produced promising results, as well as in vitro and in vivo, there is currently no cure for HGPS patients.

In collaboration with Professor Nicolas Lévy, the I-Stem team has generated induced pluripotent stem cells from progeria patients’ cells. Thanks to this unlimited and standardized biological resource they are preparing a high throughput screening campaign of pharmacological compounds in order to identify new treatments of this disease.

Progeria Reunion and Scientific Workshop

In september 2012 scientific researchers from all over the world met in Italy to share the results of their search for a treatment for progeria children. This congress was organised by Giovanna Lantanzi and Stefano Squarzoni form the University of Bologna, and made possible through donations of the Italian organisation for children with progeria: A.I. Pro Sammy Basso.
At the same time and place, all European progeria families gathered for our annual progeria reunion.

While the children enjoyed a party with clowns and jugglers, parents were informed about different plans for new steps towards a trial. Due to the efforts of high qualified researchers, parents of progeria children are now in the position that they can choose between different options for a treatment. To help them make this difficult decision, doctors explained their approach and illustrated on what grounds they expect the proposed therapy to be benificial.

options for therapy

Reducing the toxicity of progerin is possible with an FTI (Lonafarnib, and/or Vasten). The Progeria Research Foundation plans to continue the use of FTI's, perhaps in combination with an immunosuppressant drug (used to prevent rejection after organ transplantation) in the next trial. In vivo testing on mice will hopefully show that Rapamycin can improve the effectiveness of the FTI’s.

Another approach is the antisense therapy, with a morpholino. Annachiara De Sandre presented findings in research done by Carlos Lopez-Otin and her research team in Marseille. Tests on mice showed promising results, since this medication can not only reduce the toxicity, but also lower the quantity of progerin.  

The Big Run: 10 Marathons in 10 days

Charlotte Okines and Becky Reid are planning a sponsor run for the Progeria Family Circle. The route goes from Yorkshire to Kent. They will run 10 marathons in 10 days! Starting on April 5th, they hope to finish their 438 km long run on 14th of April 2012.

Charlotte always had a tough time dealing with her sisters condition, progeria. For a long time, she tried to block out what was happening. It was very difficult for her to feel so helpless. But in 2010 she helped to organise and host the UK’s first Progeria reunion, which was repeated again in 2011. This was a life-changing experience for her.

 ‘I couldn’t believe the strength, love and support between all the families, it was incredible. It made me feel strong and safe. I decided that I wanted to start raising money to make sure the reunions continue to happen as they have such a positive impact on everyone involved’. 

Charlotte and her friend Becky will start in Yorkshire, because Harry – another Progeria sufferer and close friend of Charlotte’s sister Hayley – lives there. They will then aim for Kent to meet Hayley. For more information, or to support this sponsorrun, please click HERE..

You can follow Charlotte and Becky's sponsor run on FACEBOOK

secondary school project on progeria

IES Selgas is a Secondary School in Cudillero, Spain. On the 6th of March, Dr. Carlos López-Otín, one of the most important current Spanish scientists, gave a lecture about his work for the students. The title: 'the adventure of the biochemistry of life'. After the lecture, the students asked him many questions about his research. You can read their interview here.
As a result of this project, a group of students decided to translate the information on this blog in Spanish. We will publish it. They are working on it right now! It is a big challenge for them, but this contribution helps raising awareness for progeria in Spain. Hats off to this initiative!

therapy with antisense oligonucleotide

In this video, medical students from Leiden University Medical Center show how therapy with an antisense oligonucleotide can influence the structure of an incomplete protein by masking a missing link. Like progeria, Duchenne muscular dystrophy (DMD) is a lethal disease which is caused by non a functional protein. For Duchenne and Progeria patients, this approach offers new perspectives.

It illustrates the process:
Proteins are encoded by a gene, which consists of arrays of exons (E) and introns (I). To make proteins, the introns have to be spliced out by the spliceosome. The exons are then joined together and the amino acids (AA) are synthesized.
When there is a mutation (STOP) in the gene, the protein cannot be synthesized properly and is therefore not functional. This protein makes the muscle weak, more prone to damage and eventually degenerates. An approach called 'exon skipping' could correct a faulty gene using a molecule called antisense oligonucleotides (AON). What does it do? The AON is designed to target, bind and mask/hide the mutated exon. The hidden exon will be treated as an intron by the spliceosome, and spliced out together with the other introns.
The protein produced after exon skipping will be shorter, but is expected to function better than the original, mutated protein. 

Christian

German documentary in which Christian tells about the way he copes with his condition. Once a year, he meets his friends at the progeria family circle reunion.

Progeria: Ein Leben in Zeitraffer

gene therapy for children with progeria

Scientific research into progeria has made huge progress over the last few years. In 2003 the ‘progeria gene’ was discovered by Nicolas Lévy’s team, and in collaboration with Carlos López-Otín at the University of Oviedo, in 2008, 12 progeria children were offered a clinical protocol in which two molecules were combined to slow down the process of premature aging. 

These researchers have continued their efforts to counter the consequences of the genetic defect that causes progeria.

Until now, no mouse model could accurately imitate the effects of the disease in humans. After several years of research, teams led by Nicolas Lévy and Annachiara De Sandre-Giovannoli at Inserm/Université de la Méditerranée in Marseille and by Carlos López-Otín in Oviedo have succeeded in making such a model. The lifespan of mice treated through gene therapy is significantly extended and several other parameters related to them are improved. 
The research, published October 26, 2011 in Science Translational Medicine, was made possible by the AFM thanks to donations from the Téléthon.

Carlos López-Otín

In 2003, Nicolas Lévy and his team identified the cause of the disease when they discovered the involvement of the LMNA (nuclear protein-coding) gene, lamin A/C. The mutation causes the production of a truncated protein, progerin, which accumulates in the nuclei of cells and its toxic effects cause their deformation and various other malfunctions. It has since been proven that progerin progressively accumulates in normal cells, thus establishing a link between the disease and physiological aging.

European clinical trials began in 2008 on twelve children suffering from progeria. This treatment is based on a combination of two existing molecules: statins (prescribed in the treatment and prevention of atherosclerosis and cardiovascular risks) and aminobisphosphonates (prescribed in to treat osteoporosis and to prevent complications in some forms of cancer). The use of both these molecules aims to chemically alter progerin to reduce its toxicity. However, although this treatment aimed to slow down the development of the disease, it did not reduce the quantities of progerin. To study this aspect, researchers needed to obtain a relevant animal model.

an "authentic" progeria model

To generate a model of this kind, the Spanish and French researchers decided to introduce a gene mutation (G609G), equivalent to that identified in humans (G608G), in mice to reproduce the exact pathological mechanism found in the children, with a view to then blocking it. This approach made it possible to obtain young mice that produced progerin, characteristic of the disease in humans. After three weeks alive, the mutated mice displayed growth defects, weight loss caused by bone deformation and cardiovascular and metabolic anomalies mirroring the human phenotype and considerably reducing their lifespan (an average of 103 days compared with two years for wild mice). The progerin thus produced accumulates in mouse cells via genetic mechanisms (abnormal splicing) identical to those observed in progeria children, i.e. the source of anomalies characteristic of the disease.

towards a targeted gene therapy

Using this unique progeria animal model, the researchers focussed their efforts on implementing a mutation-targeted treatment, with a view to reducing, and, if possible, preventing the production of progerin. To this end, they used ‘vivo-morpholino’ antisense oligonucleotide technology.

‘This technology is based on introducing a synthetic antisense oligonucleotide into mice’ explains Nicolas Lévy. ‘As is the case with progeria, this sequence is applied to block (or facilitate) the production of a functional protein using a gene. In this case, the production of progerin, as well as lamin A from the gene, were reduced.’

There was a highly significant increase in life expectancy of mice treated using this new technology, from an average of 155 days to a maximum of 190 days.

Nicolas Levy's team, in continued collaboration with Carlos López-Otín, now intends to translate this preclinical research into a new therapeutic trial for progeria children, possibly combined with other pharmacological molecules. Other research is being conducted in parallel to find alternative administration channels for antisense oligonucleotides.

source: inserm

other related publications by Tom Mistelli and Paola Scaffidi:
reversal of the cellular phenotype in the premature aging disease HGPS
Lamin A-dependent nuclear defects in human aging

En busca de la eterna juventud

This Spanish video (august 2011) provides an overview of medical research on ageing. 

Hayley's Story

There was no sign of the nightmare to come when Hayley was born in 1997. She had fine blonde hair, blue eyes and her parents were besotted with her. At 10 months she walked for the first time. The only concern was she was so petite and didn’t appear to be growing: at 13 months, Hayley still wore clothes for a three-month-old. Her parents took her to a specialist. Six months later a biopsy revealed her skin had an alarming lack of elasticity. In September 1999 the diagnose progeria was confirmed.

Her parents faced a difficult time, but decided that they would make her life special and pack it with wonderful memories…

Read the story of Hayley Okines Life with Progeria in old before my time.

theatre benefit show

In the past decade a bond has grown between dance school MGDance and the Progeria Family Circle. On European reunions Marianne de Pagter has been present. She always knows to put a fabulous show together with the progeria children and their siblings. For all parents it is a moving experience to see their children in a starring role on stage.

To make a new reunion possible, Marianne de Pagter now organises a spectacular theatre show with dancers and musicians from her dance school.

date: 10 sept 2011
location: theatre Junushoff, Wageningen, the Netherlands

Pre-ordered entrance cards cost €10,- and can be purchased at ronmgdance@live.nl.
All profits will go the the Progeria Family Circle.

image ©: Benno Neeleman

Mon étoile filante - the Story of Mégane and Sabrina

Sabrina Durel has two children when she gives birth to Mégane. Last of the tribe, this child is blessed and the center of attention. But soon she shows difficulties in developing normally. This mother is determined to know what's wrong, after several tests the diagnosis falls: Mégane suffers from progeria, a genetic disorder responsible for accelerated aging that leads to early death. Sabrina will fight for her daughter by challenging hospitals and physicians across the Atlantic to get to the world center for the study of this disease that no one would recognize. She seeks hope for a cure and supports Mégane in an environment that excludes different beings. But the life of Mégane and Sabrina is not just a fight. It is certainly not easy, but full of joy and happiness, pushed to the extreme face of approaching death and the overwhelming desire to live.

available in French

telomeres and progerin

A new study was published today as early online edition of the JCI, Journal of Clinical Investigation. It concludes that in normal aging, short or dysfunctional telomeres stimulate cells to produce progerin, which is associated with age-related cell damage.

Researchers from the National Human Genome Research Institute, NIH, Bethesda, Maryland, and the Department of Cell Biology and Molecular Genetics, University of Maryland in the USA have discovered a previously unknown link between Progeria and aging. Their findings provide insights about the relationship between the toxic, Progeria-causing protein known as progerin and telomeres, which protect the ends of DNA within cells until they wear away over time and the cells die.

For the first time, we know that telomere shortening and dysfunction influences the production of progerin," says doctor Leslie B. Gordon, medical director of the Progeria Research Foundation. "Thus these two processes, both of which influence cellular aging, are actually linked."

Prior research has shown that progerin is not only produced in children with Progeria, but that it is produced in smaller amounts in all of us, and progerin levels increase with aging. Independently, previous research on telomere shortening and dysfunction has been associated with normal aging. Since 2003, with the discovery of the Progeria gene mutation and the progerin protein that causes the disease, one of the key areas of research has focused on understanding whether and how Progeria and aging are linked.

R.I.P Leon Botha - 4th June 1985 – 5th June 2011

Leon Botha, a South African artist, died on Sunday from complications related to progeria, a day after his 26th birthday. Botha was one of the longest-living persons documented with the Hutchinson-Gilford Progeria Syndrome.

In 2009, Leon worked with Gordon Clark on a photo series called Who Am I? Transgression, depicting him in theatrical projections of how society might see him. This exhibition still travels around the world. Leon also held a number of art exhibitions, and as a DJ he became widely known through his association with the band Die Antwoord.

read more
Leon Botha

Leon was an inspiration to many people, shared his wisdom and touched many hearts. He will live on through his art and music.

Nestors hope

Nestor and Guillermo are the first patients whose unknown aging disease is diagnosed with a new technique, based on a complete sequencing of the genome. With them begins a new era, which will bring remarkable changes in the approach of certain diseases, including some hitherto unnoticed for science. Carlos López-Otín tells their story (Spanish)

Rare Disease Day

February 28th 2011 will mark the fourth International Rare Disease Day coordinated by EURORDIS and organised with rare disease national alliances in 25 countries. On that day patient organisations from more than 40 countries worldwide will be organising awareness-raising activities and converging around the slogan “Rare but Equal”. A multitude of events will draw attention to rare diseases and the millions of people who are affected by them.

See: Rare Disease Day 2011

"Race Against Time"

can treatment with IGF1 help children with progeria?

Carlos López Otín and his team observed that their progeroid mice had low levels of the hormone called IGF1.
They used recombinant IGF protein produced in the laboratory to treat the mice and the results were positive in terms of extension of longevity and improvement of progeria symptoms.
The improvement was clear and significant, but lower than that observed with the combination of statins and bisphosphonates which they reported two years ago in Nature Medicine and which has been the basis of the current clinical trial, first conducted by Dr. Nicolas Lévy in Marseille and adopted by the American Progeria Research Foundation in Boston.
The good thing is that additional - yet unpublished work - indicates that positive effects of IGF (albeit not so impressive) could be additive to the pharmacological treatment. Another good thing is that IGF1 has been widely used in children with Laron syndrome with no adverse effects.

Although this finding is interesting, researchers are very cautious regarding immediate translation of laboratory findings in animal models to patients. The option to add IGF to children treated with statins-bisphosphonates will be discussed, for the moment these children will have an adequate follow up of the current treatment that is offered in Marseille.

new development in research

The group of researchers led by Carlos Lopez Otin at the University of Oviedo, has found that insulin growth factor - or IGF1 - extends life in an animal model of human premature aging. The work was published yesterday.

The treatment developed by these researchers can extend a 25 percent longevity of mice with progeria. According to the authors, this represents an important step toward understanding the mechanisms involved in the development of this disease. In addition, it raises a new therapeutic option for patients affected by syndromes of accelerated aging, those who develop during the first years of life characteristic symptoms of old age: osteoporosis, loss of subcutaneous fat and hair, and cardiovascular failure, among others.The life expectancy of people with the most common form of progeria syndrome, Hutchinson-Gilford-is less than 20 years.

The scientists used genetically modified mice created previously in his laboratory. And they found that levels of a hormone known as insulin-like growth factor or IGF1 were abnormally low in these conditions. They decided to restore hormone levels, and treatment with IGF1 led to a marked improvement in various alterations in these mice, including weight gain, recovery of subcutaneous fat and locomotive ability, reduced hair loss and increased significant life expectancy.

According Otín, this paper raises an option "to improve the clinical situation and extend the life of those suffering from premature aging." In work previously published in Nature and Nature Medicine, the same researchers from the University of Oviedo reported that the accelerated aging was associated with abnormal activation of protective mechanisms against cancer and designed a pharmacological strategy aimed at blocking the accumulation protein responsible for this disease. This work has led to an international clinical trial, currently underway in Marseille, to treat children suffering from this dreadful disease.
spanish source