At the 12th ISDS, Prof. Ravi Savarirayan, a paediatrician and clinical geneticist at Murdoch Children Research Institute, gave a lecture on the “Advances in Treatments of achondroplasia”. In his lecture, he gave an overview of achondroplasia and its associated pathologies, referring to the paper “Optimal management of complications associated with achondroplasia” PJ Ireland, Appl Clin Genet. 2014, and also mentioning the social constraints. Dr. Ravi is coordinating the clinical trial phase 2 study of BMN-111 and he focused mainly on talking about the BMN-111 study. He did not reveal updates about this subject.

Following Prof. Ravi lecture, one of his post-doc, Dr. Patrick Yap, gave a presentation on: “Best practices in evaluation and treatment of stenosis of the foramen magnum in achondroplasia during infancy“. This presentation was the result of the second meeting of the Skeletal Dysplasia Management Consortium – SDMC, a very interesting project composed by renowned geneticists, pediatricians, radiologists and orthopedists and researchers working in skeletal dysplasia.

At the SDMC last meeting, on October 2014, the members developed a manuscript titled “Best Practices for the Management of Foramen Magnum Stenosis in Individuals with Achondroplasia”.

The conclusions of this document are based on a very interesting method, the method Delphi, wherein the experts could choose based on concepts described, with tracking lines and more appropriate medical guidelines based on clinical observations.
In conversation with Dr. Ravi and Dr. Patrick at the end of both presentations, we talked about the approach to the prevention of ACH morbidities as well as forms of foramen magnum compression monitoring without the use of MRI: transfontanellar ultrasound and palpation of the frontal fontanella, until 2 years-old, that is the average age limit of increased occurrence of stenosis of foramen magnum.

Slide from Dr. Patrick Yap presentation

The conclusions of the SDMC meeting for the procedures in case of stenosis of the foramen magnum in achondroplasia were:

1. The increased mortality rate observed in children with achondroplasia is largely associated with cervical spinal cord compression

2. The recommended surveillance MUST include the natural history of the patient, physical examination and polysomnography in all children with achondroplasia

3. Polysomnographic studies should evaluate the syndrome of obstructive sleep apnea, hypoxia, hypercapnia and ECG

4. Neuro-axial imaging (MRI) only recommended if necessary

5. Decision-making for the decompression of the FM, with better guidelines for standardized care, was revised and improved.

These guidelines to improve medical and surgical practice are of the greatest importance, once it is obvious that the assessment of a child with a FM stenosis is conflictual and because of that, is hard to achieve a consensus . For that reason, having more than one opinion before deciding the resolution a case of stenosis increase the chance of a reasoned decision.

Goal for  the next SDMC meeting: reducing morbidity and mortality.

We will be waiting for the next SDMC meeting conclusions.

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The school is the world, a very important step for the growth of all children worldwide. It is essential to start educating in respect for differences from the earliest stages of education, because children are permeable and ductile and, if they receive a thorough orientation and are made aware, their nature is always ready for understanding and generosity .

So one of the first projects of the ALPE Foundation was developing material for schools that would be useful for teachers to introduce not only dwarfism, but any other disabling condition or concepts like inclusion and respect for difference the classrooms. The booklet for schools has been reissued several times in Spanish, English and Spaniard and remains a valuable tool for introducing in schools the dwarf not always simple theme.

Also the publication” Let the sun rise” and “The little prince in the lost kingdom” serve this function as a base material for schools and families and to read about achondroplasia in a fun and educational way. In addition, the foundation developed adaptations for materials and school furniture, teaching guidelines on how to prevent and deal with conflicts and ensure a healthy integration of children or the psychological and social problems often hard to take for those who have not lived disability or dwarfism closely. We also visited personally, we or our collaborators specialists in education, schools to talk with teams of teachers, and even with students, when we deem it necessary or positive. Constantly we send information to schools throughout Spain and Latin America.

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BioClin Therapeutics has a leading product, the B-701, that is an anti-FGFR3 mAB (this means that is a monoclonal antibody), that is under developed for the treatment for metastatic bladder cancer. At the same time, BioClin has announced that is evaluating B-701 for achondroplasia. Some other antibodies for FGFR3 have been studied before for achondroplasia.

This study from BioClin is related to the article: “Redesigning a Monospecific Anti-FGFR3 Antibody to Add Selectivity for FGFR2 and Expand Anti-tumor Activity“, Carter PJ et al, Mol Cancer Ther. 2015. Aug 12. pii: molcanther.1050.2014.

In this study an anti-FGFR3 antibody was redesigned to create function-blocking antibodies that binded with dual specificity to FGFR3 and FGFR2.

An antibody is a protein that combines to a specific protein called an antigen. Antibodies circulate throughout the body until they find and attach to the antigen. Once attached, they can recruit other parts of the immune system to destroy the cells containing the antigen. Researchers can design antibodies that specifically target a certain antigen and then make many copies of that antibody in the lab. These are known as monoclonal antibodies (mAbs), and they have many uses in research, treatment and diagnosis.

Credits: http://www.nature.com/nchembio/journal/v4/n6/images/nchembio0608-326-F1.jpg

What is connection between mutant FGFR3 in achondroplasia and antibodies?

FGFR3 mutation causes a gain-of-function of this receptor in achondroplasia and also in a variety of cancers, where this mutation increases the receptor signalling and enhances negative regulation of growth plate chondrocyte proliferation.

Most, if not all, potential solutions to treat achondroplasia until now have been directed to the mutant FGFR3 in chondrocytes.

And why this potential new treatment has to be looked in a very careful way?

Antibodies are typically large proteins and only very small molecules can reach the growth plate. So this is the main issue that rises in this new potential approach to achondroplasia. Will it be possible to use of an antibody to treat achondroplasia?

Credits:https://commons.wikimedia.org/wiki/File:Intact_antibodies_and_a_variety_of_antibody_fragments.png

BioClin Pipeline for B-701

B-701 is in preclinical testing for achondroplasia for which FGFR3 antagonism may be beneficial. BioClin has completed a 6-month dosing study in juvenile monkeys and they are conducting further studies to advance this program.

Credits: BioClin Therapeutics http://www.bioclintherapeutics.com/pipeline.html

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It is with great joy that we share this news:

On October 1st will be held at the fairgrounds pavilion Liberbank “Luis Adaro” in Gijon, the award ceremony for the “Ambassadors of Gijon” 2015. Carmen Alonso Alvarez will be awarded for her work as head of the ALPE achondroplasia Foundation, working for achondroplasia since the year 2000. ALPE Achondroplasia Foundation has organized five International Congresses of achondroplasia, including multiple sessions, workshops and specialized meetings.

ALPE is an organization based in Gijon, in the north of Spain, fighting for the rights, welfare and social integration of people suffering from this variety of bone dysplasia.

News from Business and Tourism Club pf the Principality of Asturias.

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On the 1th October 2015, the coordinator of the ALPE Foundation, Carmen Alonso, received the award of “Ambassadors of Gijon” in 2015, in recognition of the city that houses ALPE achondroplasia Foundation for the last 15 years, “a place free of prejudice where families feel at home. “

Carmen Alonso received Principality Enterprises Club of Business and Tourism award, for her work and for involvement in the development of laws and decrees and for her contribution to the society of Gijon and Asturias.

Carmen Alonso stressed while receiving the distinction: “We like the welcoming nature of the people of Gijon” and “The respect and care for the others makes this city special.” In addition, “The city of Gijon is ALPE and all the families who visited us are aware of this from the first moment“.

For Carmen, the prize went to Yago, hes son, born “with the almost unknown disability that marked the turning point in my life,” to Nacho, her husband “he has always supported us“, to the ALPE team because “without them and their perseverance and proximity, this would not have been possible.” Also for the patronage of the Foundation, for the professionals, for her friends and for “so many families around the world and adults that every day trust us.”

Viva Carmen!

Sources: El Comercio and La nueva España

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Representing ALPE Achondroplasia Foundation, Carmen Alonso (coordinator of the Foundation) and Inês Alves (scientific advisor) attended the 8th National Spanish Congress for Rare Diseases. “Joining experiences, promoting realities” was the motto of this congress held in Murcia from October 15 to October 18, organized by the Association of Rare Diseases D’Genes in collaboration with the Murcia delegation of FEDER and the Association of Relatives and Affected by Lipodystrophies (AELIP).

Juan Carrion defined the motto speaking about “the need to keep sharing knowledge and to fight all that rare diseases that are considered a social and health priority in all national health systems around the world.”

Around five hundred people attended this conference. According to the organization there were present 16 countries, 250 people assisted the sessions by live streaming, more than 65 representatives of associations of rare diseases, 80 speakers, 102 posters and many discussions and interesting interventions.

The quality and quantity of the papers have made this meeting a unique place to learn, share, contact with professionals, patients, families, pharmaceutical industries and administration. The congress venue, the Catholic University San Antonio of Murcia (UCAM), was a magnificent place to visit and see.

One day before the congress, Country Manager for Spain and Portugal of BioMarin, Tiago Barros and the ALPE coordinator, Carmen Alonso, visited the facilities of the new Multidisciplinary Center Celia Carrión Pérez de Tudela. During the visit they were accompanied by the coordinator responsible for D’Genes and president of AELIP, Naca Eulalia Perez de Tudela, who explained the services that are provided at the center.

ALPE Foundation presented a poster at the congress on aquatic therapy in achondroplasia. The technical and scientific information used for this work was collected by the physiotherapist Carmen Barreal, product of her research in ALPE Foundation. We highly appreciate her work as well as photos for this project. We also like to thank the people who appear in the photos for their generosity.

Here you can see the poster presented in high resolution: Terapia acuática FEDER ALPE – PDF

Tiago Barros, Carmen Alonso and Inês Alves

The poster assessment by the jury, whom have made very good suggestions for a next project.

Inês Alves during the evaluation of the poster

In addition to the sessions and panel discussions, there was time to share with families. This time of proximity is a basic principle of ALPE. There is always time for families!

Encarna Torres, Marina´s mother, Carmen, Inês y Marina,  4 years-old girl, that has metatropic dysplasia

This event is very relevant for rare diseases in Spain and in Latin American countries.

A rare disease affects a very small percentage of the population. Most rare diseases are genetic and are present throughout the life of a person, even if symptoms do not immediately appear. In Europe a disease or disorder is considered rare when it affects 1 in 2000 citizens.

Worldwide, as an example, the average incidence of achondroplasia is  calculated to be 1 in 25.000 live births.

Rare diseases are characterized by a wide variety of disorders and symptoms that vary not only according to the disease but also by the patient suffering the same disease. Relatively common symptoms can hide underlying rare diseases, leading to misdiagnosis.

It is estimated that the number of people in Europe who suffer from a rare disease is over 30 million in a population of 503 million people, representing between 6 and 8% of the population of the European Union. Rare diseases affect not only those diagnosed but also their families, friends, caregivers and people throughout society.

In this congress, there were several highlight sessions:

• The importance of involving patients in the Spanish National Health System
• Real access to diagnosis and treatment, a right to more than 3 million people
• Roundtable: media coverage of Rare Diseases
• Roundtable: Models of multidisciplinary care for patients with rare diseases
• Roundtable: Current status of ER in Spain and experiences in Latin America

In the last day, several workshops took place. We mention a very interesting “Rare diseases: Frequent changes in feeding”, by Begoña Barceló.

Workshop: Rare diseases – frequent changes in feeding

The closing ceremony included children that attended the congress and that were dressed as the popular Minions drawings, symbolizing researchers that cure rare diseases.

The post ALPE representation at the FEDER congress appeared first on ALPE.

ALPE Foundation was represented at the WODC by Inês Alves, our scientific adviser. The congress meeting went  for two days, with more than three hundred participants: pharmaceutical companies, scientists, representatives of regulatory agencies of the European health associations and patient organizations. During this congress, it was clearly showed that the pharmaceutical industry is beginning to see the patient closely and in a human and social perspective, and want to know the patient.

The patient has become the central element, as evidenced by the growing relationship between patient organizations and the pharmaceutical industry in the upstream and downstream of the marketing of new medicines, as a valid interlocutor to define objectives and strategies and satisfy demands and needs. The experience of rare disease patient, making it the most knowledgeable of it, is an axis in the whole process of scientific development and contribute substantially to technical knowledge.

The importance of the patient was one of the highlights of the congress topics, as they are central to a better understanding of the natural history of a rare disease, i.e. how the rare disease advances and manifests itself and what characterizes it. And who better to share this knowledge if not the patient!One of the great values ​​of this congress was the variety of the origins of the speakers and participants of groups of rare diseases and the ties and bridges that were established. The personal involvement of agents of the pharmaceutical industry with the patients, the need of mutual understanding and the motivation that engages the industry people to work more and harder to find new therapies is the new paradigma. It was very interesting the topics discussed by specialists throughout the congress and all the panels discussions offered the opportunity of close interaction between attendees from various sectors in which all could expressed questions, concerns, experiences and even suggestions.

Definitely this was an excelent congress, organized by Terrapinn.

The post The World Orphan Drug Congress, 12-13 November 2015, Geneva appeared first on ALPE.

The University Institute of Integration in the community, INICO, and the North Group Foundation organized the 13rd International Photography Contest “People with disabilities in everyday life.

“Maia”, the photograph of a child with achondroplasia, by the Spanish author Andrés Gómez won first prize. The jury praised the extraordinary quality of the images presented in this edition and stressed the difficulty of choosing the winners among the 688 received photographs. A total of 385 professional and amateur photographers from 14 countries participated in this event, which over the years has become a reference in Spain and Latin America.

This image is part of the project “More than an image” that Andrés Gómez is developing for ALPE Foundation. This project aims to bring to the European society the lives of people with this genetic condition through photography. People with achondroplasia with different ages pose for the author in attitudes and actions that show their most personal and everyday aspects: hobbies, employment, lifestyle. We believe that knowledge is respected and, therefore, this is an approach to the society of real people, with a distance of stereotypes just sharing  their life with the world in its essence.
This project is yet another way to show the integrity of people with dwarfism. This consists, among other projects, in the work done by ALPE Foundation and awards like this recognition and a mean of disclosure. And this picture is undoubtedly excellent!

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This review by Kendra A. Klag and William A. Horton, was published very recently in Human Molecular Genetics, Journal 2015.

Here are the major lines of this review. You can find a more extensive and comprehensive text of this work in our library.

“Achondroplasia (ACH) is the prototype and most common of the human chondrodysplasias. It results from gain-of-function mutations that exaggerate the signal output of the fibroblast growth factor receptor 3 (FGFR3), a receptor tyrosine kinase that negatively regulates growth plate activity and linear bone growth. Several approaches to reduce FGFR3 signaling by blocking receptor activation or inhibiting downstream signals have been proposed. Five show promise in preclinical mouse studies. Two candidate therapies target the extracellular domain of FGFR3. The first is a decoy receptor that competes for activating ligands. The second is a synthetic blocking peptide that prevents ligands from binding and activating FGFR3. Two established drugs, statins and meclozine, improve growth of ACH mice. The strongest candidate therapy employs an analog of C-type natriuretic peptide (CNP), which antagonizes the mitogen-activated-protein (MAP) kinase pathway downstream of the FGFR3 receptor and may also act independently in the growth plate. Only the CNP analog has reached clinical trials. Preliminary results of Phase 2 studies show a substantial increase in growth rate of ACH children after six months of therapy with no serious adverse effects. A challenge for drug therapy in ACH is targeting agents to the avascular growth plate. The application of gene therapy in osteoarthritis offers insights because it faces similar technical obstacles. Major advances in gene therapy include the emergence of recombinant adeno-associated virus as the vector of choice, capsid engineering to target vectors to specific tissues, and development of methods to direct vectors to articular chondrocytes.”

Image credits also from: “Advances in treatment of achondroplasia and osteoarthritis”,Kendra A. Klag, William A. Horton, Human Molecular Genetics, Journal 2015.

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This is the new science! The genetic editing technology CRISPR-Cas9 can be an enormous promise for genetic diseases, including achondroplasia, being the most efficient method of gene editing available today.

Emmanuelle Charpentier, French and Jennifer Doudna, American, received this year the Princess of Asturias Award for Research, and Science magazine raises this technique to the number one in the list of scientific discoveries of the year. This tool called CRISPR-Cas9, commonly known as “genetic cut and paste“, is attracting researchers around the world for its plasticity, ease of use and low cost. For this procedure, science is now closer to cure diseases for which there were no treatments or even prevent diseases in an individual and subsequent generations, now rising ethical issues because it involves acting on the embryo to change the DNA.

This technology can have major impact in rare diseases “Because there are very few patients and many diseases that are usually generated by mutations in one or more genes. Before much time was needed to study only one variation of the genome responsible for these diseases but now, in a few weeks, you can reproduce a mutation in a mouse and see what happens.” Luis Montoliu, Nacional Biotecnology Center.

The CRISPR-Cas9 method is simple to use and versatile in its function. It promises to make gene editing more accessible and cheaper, allowing everyone from major companies and amateur biohackers the opportunity to test their creativity and partake in the genetic revolution.

Best news is recently published a study about the verasitility of CRISPR and application in achondroplasia.

“Pathogenic mutations can be broadly classified as causing either gain or loss of function in a gene product. The gain-of-function mutation in FGFR3 in achondroplasia, results in the expression of a pathogenic gene product and may be treated by using NHEJ-mediated mutations to specifically inactivate the mutant allele while leaving the wild-type allele intact on the homologous chromosome.” Zhang et al., “Therapeutic genome editing: prospects and challenges“, 2015 Nature Medicine.

The enormous excitement surrounding genome editing needs to be coupled with strategic planning and rigorous but enabling regulatory processes to ensure the successful development of this class of potentially life-changing medicines. The technology will require a number of iterations to systematically optimize its efficacy, safety and specificity. Although still in its infancy, genome editing presents tantalizing opportunities for tackling a number of diseases that are beyond the reach of previous therapies. Given the accelerating pace of technological advances and broad range of basic science and clinical applications, the road ahead will undoubtedly be an exciting one.

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Since 1994 the identification of the gene responsible for achondroplasia, a form of dwarfism, medical and scientific research teams are trying to find a cure. Since 2014, a clinical trial is being conducted on children aged 5 to 13 years old and the first results are promising.

In achondroplasia, the FGFR3 gene is mutated and this receptor 3 of FGF´s (FGFR3) in chondrocytes (the cells in the growth plate) produces negative signals in large quantities. And this inhibits the natural growth rate. The treatment that is now been under study is actually another small protein with is another receptor, that is able to block inside the chondrocytes, the abnormally active FGFR3. It is a chain reaction that researchers first tested on human cells and mice.

Here you can see a video (in french)

The research was conducted in the laboratories of the Institute of genetic diseases, in Paris. Comparisons were made between the mice with achondroplasia treated with the protein and mice with achondroplasia untreated. The results were that the researchers found a particular difference in size between the femur of treated and untreated mice. The mice that were treated with the BMN-111 molecule had a longer femur than the untreated mice.

BMN-111 allowed the mice to grow by 10% in twenty days, with daily injections. For researchers, this experimental treatment is a step forward. “Not only it can modify cell proliferation, also it is able to modify cell differentiation. These are extremely important points because these cells do not proliferate well and do not differ much … and do not allow the bone to grow properly, “says Dr. Laurence Legeai-Mallet, director of research at the Institute of Genetic Diseases of Paris.

Twenty-six children in the world are under clinical study for this new drug. Two French children were selected for this clinical trial. Since the beginning of the experiment, the researchers observed an improvement in growth in all children. The laboratory that conducted the tests has also decided to extend testing for two years.

Based on an article of: FranceTvinfo

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My parents weren’t familiar with the words Achondroplasia, short stature or dwarfism until I was born. Many people told them that I was not going to ‘thrive.’ Very little was known about my condition at that time, leaving them in the dark about what my future may hold. Saving every article and pamphlet she could get her hands on, my mother hoped for information and answers regarding my condition.

Beginning in my infancy, my parents found an orthopedic surgeon in Baltimore, MD who specialized in skeletal dysplasias. At the age of 3, I was braced for Kyphosis and from that point on we made a trip to Baltimore every year to monitor my progress.

As a child growing up, I was unstoppable. In my mind, there was nothing that I could not do. Swimming, softball, cheerleading and skiing were just some of my favorite activities. But as I got older, things became increasingly more difficult. When walking longer distances, I tired very easily and felt constant aching in my legs. Pain in my elbows and hips, which I ironically labeled as ‘growing pains,’ became constant. My lower legs were becoming severely bowed and my doctor immediately recommended surgery. Back then, the method was to shave away the part of the bone causing a bowed appearance. The thought of such a procedure didn’t sit well with me.

That is when we first came across the extended limb lengthening procedures on a televised segment of Regis and Kathy Lee. Two young boys were on the show with external fixators on their legs. Immediately, I was intrigued and wanted to know more.

Knowing that surgery was inevitable, we began to look deeper into extended limb lengthening. After several failed consultations with inexperienced practitioners, we found Dr. Paley, also in Baltimore, MD, at Kernan Hospital. At my first consultation, he explained that I was an excellent candidate for surgery and that several of the deformities that I suffered from would be corrected. That was all I needed to hear.  The height and proportion were an added bonus. With all of the pros and cons weighed and full support from my family and friends, I opted to undergo the procedures.

My first operation was in June of 1998. I’d be lying if I said it was easy. The rigorous physical therapy was intense. Vigilance paid off and with only two instances of pre-consolidation and a few pin infections, my first procedure gifted me a new sense of independence and pride. Over the course of 6 months, my lower legs were lengthened 6 inches and beautifully straightened.

Wanting to ‘just go for it, ’I underwent the lengthening on my arms the following spring in 1999. What a piece of cake that surgery was compared to the lower leg lengthening. A mere 4 months later, I could rest my arms comfortably at my side and put my hands in my pockets – the ‘growing pains’ previously felt in my elbows were gone.

The final lengthening on my upper legs, the femurs, was by far the most difficult. During the lengthening phase I was non-weight bearing and confined to a wheelchair. Going from newfound independence to being completely reliant on others was not easy for the free spirited teenager that I was. But I knew that it was all for good reason. I spent my sophomore year of high school primarily being tutored at home. In the end, the positives outweighed the physical limitations and after 6 months the flexion deformity in my hip was gone and I had gained another 5 inches of length.

To this day, I will never forget the feeling of standing up next to one of my best friends for the first time, eye to eye. Or the moment that I sat in a chair and both of my feet touched the ground. You can’t put those moments into words but they gave true meaning as to why I chose to undergo the procedures.

When I first began the limb lengthening surgeries, I knew there was enormous controversy surrounding them. The Little People of America deemed the procedures cosmetic and claimed that those who chose to lengthen did it to blend in with society, ultimately wanting to change who they were. I held true in knowing that my motivation did not lie in becoming taller, blending in or changing who I was. My eyes and my heart were on my future. I was still going to be Kristen, the girl born with dwarfism. Nothing could ever change that.

Gradually, people are becoming less objective to limb lengthening and I believe it is because those of us who have gone through with the procedures continue to open up about our experience. Many times, parents of average height who have a child with short stature inquire about limb lengthening, wanting to pursue it for their child. One thing I always stress is that I made the decision to go through with the surgeries. My parents would have supported me either way. It requires commitment from both sides – everyone is in it together. The success outweighs the occasional pain and setback. It is so important for the individual undergoing the procedures to not only be fully committed but ready for it; to understand everything surgery entails. Limb lengthening isn’t for everyone and that is OK.

Never in my wildest dreams could I have imagined that modern medicine would shape my life the way it has. Yes, I am taller, proportionate and straighter thanks to the procedures. It took perseverance, tears and strength. And for almost four years I was constantly in and out of the hospital. But the true immensity of the experience as a whole is nearly impossible to put into words.

When I was a little girl I would pray to God that I would wake up in the morning and things would be different. People would stop looking at me like I was an object of ridicule and accept me for who I was as an individual, not what I looked like. To say that my prayers have been answered is an understatement. Throughout the years I have crossed paths with people who have taught me courage, strength, compassion and how to love me for who I am. The entire journey has softened my heart. I have no regrets but immense gratitude for everything and everyone that this experience has gifted me.

When you face your illness or condition as a disability – it becomes a prison. When you acknowledge your illness or condition as an identity – it is a source of freedom. My name is Kristen and I am a woman with dwarfism who has undergone extended limb lengthening. Thank you Dr. Paley for using your gifts to help me make little, HUGE.

Kristen
Charleston, South Carolina

Credits: Paley Institute

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On the 10th of March 2016, will take place in Oviedo, in the northern of Spain, the MasterClass “Orphan Drugs and Rare Diseases”, oriented to professionals, associations of patients affected with the special issues and circumstances of orphan drugs, the entities involved in the European Medicines Agency  (EMEA) and regulatory institutions that act on research, production and distribution of these drugs.

 ALPE Foundation is involved in the organisation of this event and will participate in the opening session at 9 am.

The program will be the following:

You need to register through the email: masterclass@skylineventos.com,  before the 1st March.
We ask you to disclose this information to all who may be interested: medical profesionals, researchers, pharmacists, patients associations.

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The 29th February 2016 is the Rare Disease Day.

Rare diseases are diseases, conditions, syndromes or disorders that affect a small number of people compared to the general population. And because of their rarity, they pose specific questions. In Europe, it is considered that a disease is rare when it affects 1 person in 2,000. A disease can be rare in one region, but common in another. There are also many common diseases whose variants are rare.

There are thousands of rare diseases. Until now, were already discovered 6000-7000 rare diseases and new diseases are regularly described in the scientific literature. The number of rare diseases depends on the degree of specificity used to classify the different disorders. So far in the field of medicine, disease is defined as an altered state of health, presented with a unique pattern of symptoms and with a single treatment. 70% of patients with rare diseases suffer some kind of disability.

From orphanet

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The journalist Borja Roberts, from the news agency Colpisa, requested the collaboration of our scientific advisor, Inês Alves, for a story on the CRISPR-Cas 9, for the Day of rare diseases, which is always held on the last day February.

Below, you can read the full report in the Journal of Navarra the 02/29/2016:

The latest genetic revolution seeks to respond to rare diseases

Biotechnology lives these days such a large and surprising revolution, but after it can be the solution to many congenital diseases, those affected by rare diseases are still few who know what goes on in laboratories. A new genetic technique called CRISPR-Cas9 edition, identified three years ago. Correct defective DNA of cells in a living animal is no longer a utopia. And though hardly ait is taking the first steps, progress is getting faster and with more solid results.

“In two and a half years we have gone from having a promising technique to be sure it works,” says Luis Montoliu, researcher at the National Center for Biotechnology (CNB – CSIC) and member of the Spanish network of research on rare diseases. “In addition, advances are so rapid that we are running out of excuses for not using them.” Until the arrival of CRISPR-Cas9, modify the DNA was an expensive, difficult and full of bugs process. Too risky for almost any medical use. Yet, except once, it was used only in animals. In 2015, Science magazine called CRISPR-Cas9 as the most important scientific breakthrough of the year. Around the same time, major scientific organizations in the US, China and Britain agreed to not use it to modify germ cells, which transmit genetic information to offspring for fear of unexpected consequences.

“And was surpassed in two months,” says Montoliu. At the end of January 2016c, three independent teams of scientists came public that they managed to treat Duchenne muscular dystrophy, a degenerative genetic disease that causes the disappearance of the fibers forming the muscles in adult mice. None of the works had healed completely, but all had managed to regain fitness and muscle tone. One of them also managed to prevent the mutation that causes the disease to their offspring should be transmitted in four out of five cases.

These results are the most exciting for Montoliu, which ensures that the arrival of CRISPR-Cas9 has brought a new group of young researchers. “We were spellbound with the potential at the embryonic level, but we have a therapeutic tool that can help to treat patients that exist today,” he says. “We may not get a complete cure, but in many diseases an improvement of 10% or 20% is sufficient to raise the quality of life of patients and reduce their risk of death.”

Inês Alves, a veterinary doctor, mother of a three years-old child with a rare disease that causes a form of dwarfism, achondroplasia, and also the scientific advisor of ALPE achondroplasia Foundation, also looks at CRISPR-Cas9 with hope. “Probably it won´t arrive in time for my daughter, but I know we’re not very far from achieving a cure,” she says. “And this will help children who are being born now or arriving in the coming years.” As achondroplasia slows bone development during growth, any intervention has to be done before the child with achondroplasia stop growing. “Any treatment has to be done before 15 years-old,” emphasizes Inês Alves. “And the sooner the better.” A few months ago, she explains, she spoke with one of the companies that are beginning to develop therapeutic tools with this technology and the CEO of one company said that this achondroplasia, which is caused by a mutation in a single gene, is one of the candidates to have a cure soon . “Apparently, changing the DNA is not difficult, the difficulty is to make CRISPR-Cas9 get where it needs to go.” said Inês.

Getting CRISPR-Cas9 reach the affected organs is not trivial, although there are proposals. Each treatment will need its own strategy. According to what the disease affects, it will be needed to correct the DNA of cells of the retina, muscles, brain or any other organ. Not all are equally easy.

The first candidate disease to receive treatment with CRISPR-Cas9 is Leber optic nerve atrophy. The first clinical trial is planned for 2017. And yet, the Spanish association affected by this disease (Asanol) had not yet heard of this technique, too recent and advancing at a breakneck pace.

Image credits: Science of singularity

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Congress Program

08h50: Opening note.

09h00:I ntroduction to Bone dysplasias: definition, classification and epidemiology.

09h20: Prenatal diagnosis.

09h40: Clinical examination of children with probable bone dysplasia.

10h00: Radiographic assessment: clues to the diagnosis.

10h20: Discussion

10h40: Coffee break.

 11h00: Achondroplasia and other chondrodysplasias associated to FGFR3.

11h20: Spondyloepiphyseal dysplasia congenita and other diseases associated with type 2 collagen.

11h40: Discussion.

11h50: Metatropic dysplasia and other diseases associated with TRPV4.

12h10: Pseudoachondroplasia and multiple multiple epiphyseal dysplasias.

12h30: Bone dysplasias and multiple dislocations.

12h50: Discussion.

13h00: Lunch.

14h00: Mucopolysaccharidosis: from diagnosis to treatment.

14h20: Osteogenesis imperfecta.

14h40: Debate

14h50: Fundamental principles in the treatment of limbs in bone dysplasias.

15h10: Challenges in the surgical treatment of boné dysplasias.

15h30: Treatment of spine pathologies in dysplasias Bone.

15h50: Discussion.

16h00: Coffee.

16h20: Rehabilitation bone dysplasias.

17h00: Obesity and bone dysplasias.

17h20: Diagnosis, evaluation and treatment of bone dysplasias: what‘s new and future perspectives.

18h00: Discussion

18h10: Clinical cases and optional evaluation.

19h00: Closing

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Desde 1994, cuando fue identificado el gen responsable de la acondroplasia, una forma de enanismo, los equipos de investigación médica y científica están tratando de encontrar una cura. Desde 2014, un ensayo clínico se lleva a cabo en niños de 5 a 13 años y los primeros resultados son prometedores.

En la acondroplasia, el gen FGFR3 está mutado y este receptor 3 de FGF (el FGFR3) que existe en los condrocitos (las células en la placa de crecimiento) produce señales negativas en grandes cantidades. Y esto inhibe la tasa de crecimiento natural. El tratamiento que ahora ha sido objeto de estudio es en realidad otra proteína pequeña, otro receptor, que es capaz de bloquear en el interior de los condrocitos, el FGFR3 anormalmente activo. Es una reacción en cadena que los investigadores ensayaron primero en células humanas y ratones.

Aquí puede ver un vídeo (en francés)

La investigación se realizó en los laboratorios del Instituto de enfermedades genéticas, en París. Se realizaron comparaciones entre los ratones con acondroplasia tratado con la proteína y los ratones con acondroplasia sin tratamento. Los resultados fueron que los investigadores encontraron una diferencia particular, de tamaño entre el fémur de ratones tratados y no tratados. Los ratones que fueron tratados con la molécula de BMN-111 tenían un fémur más largo que los ratones no tratados.

El BMN-111 permitió a los ratones crecer en un 10% en veinte días, con inyecciones diarias. Para los investigadores, este tratamiento experimental es un paso adelante. “No sólo puede modificar la proliferación celular, también es capaz de modificar la diferenciación celular. Estos son puntos muy importantes debido a que estas células no proliferan bien y no si difieren mucho … y no permiten que el hueso crezca adecuadamente”, dice Dr. Laurence Legeai-Mallet, directora de investigación en el Instituto de Enfermedades Genéticas de París.

Veintiséis niños en el mundo están bajo el estudio clínico de este nuevo fármaco. Dos niños franceses fueron seleccionados para este ensayo clínico. Desde el comienzo del experimento, los investigadores observaron una mejora en el crecimiento en todos los niños. 

El laboratorio que realizó las pruebas también ha decidido ampliar las pruebas durante dos años.

Basado en un artículo de: FranceTvinfo

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Traducimos el testimonio de una joven que ha atravesado un proceso de elongación ósea con la mirada puesta en el futuro. Ni olvida la dureza de la experiencia ni se engaña sobre su acondroplasia. Siempre tendrá acondroplasia. Es una mirada serena hacia atrás, hacia lo superado pero no olvidado.

Mis padres no estaban familiarizados con las palabras «acondroplasia», «talla baja» o «enanismo» hasta que yo nací.  Muchos les decían que no iba a «salir adelante». Se sabía muy poco sobre mi condición por entonces y estaban a oscuras sobre lo que mi futuro podía traer. Atesoraban cada artículo y folleto que caía en sus manos.

Encontraron durante mi infancia a un cirujano ortopédico en Baltimore especializado en displasias esqueléticas. Con tres años me operé de cifosis y desde ese momento hicimos un viaje anual a Baltimore para controlar mi evolución.

Como todo niño, yo era imparable. En mi mente no había nada que no pudiera hacer. Natación, softball, animar fútbol o esquiar eran tan sólo algunas de mis actividades preferidas. Pero según fui creciendo las cosas se volvieron cada vez más difíciles. Cuando caminaba distancias largas me cansaba rápidamente y siempre me dolían las piernas. El dolor en los codos y las caderas, que llamé, irónicamente, «dolores de crecimiento» se hizo constante. Se me curvaron las piernas mucho por abajo  y mi doctor indicó cirugía inmediata. Por entonces, el método consistía en quitar la parte del hueso que aparecía curvada. Pero yo no conseguía aceptar la idea de semejante procedimiento.

Fue entonces cuando vi por primera vez algo sobre los procedimientos de elongación ósea en un programa de Regis y Kathy Lee. Se veía a dos chicos con fijadores externos en las piernas. Inmediatamente me sentí intrigada y quise saber más.

Sabiendo que la cirugía era inevitable empezamos a investigar sobre la elongación ósea. Tras varias consultas fallidas con ciruganos sin experiencia, encontramos al Dr. Paley, también en Baltimore, en el Hospital kernan. En mi primera consulta explicó que yo era una candidata perfecta para la cirugía y que varias de las deformaciones que yo sufría serían corregidas. No necesité oír más. La altura y la proporcionalidad fueron un extra añadido. Con todos los pros y contras sopesados y apoyo total por parte de mi familia y amigos, decidí someterme al procedimiento.

Mi primera operación fue en junio de 1998. Mentiría si dijera que fue fácil. La terapia física fue intensa. Pero la atención pereció la mena y con tan sólo dos episodios de pre-consolidación y unas pocas infecciones de clavos, mi primera elongación me proporcionó una sensación nueva de independencia y orgullo. En un periodo de 6 meses, mis tibias fueron alargadas 6 pulgadas y se enderezaron maravillosamente.

Quise ir a por todas y me sometí a la elongación de brazos la primavera siguiente, en 1999. Aquello fue facilísimo comparado con la elongación de piernas. Tan sólo cuatro meses más tarde podía dejar los brazos tranquilamente a los lados de mi cuerpo y meter las manos en los bolsillos. Los «dolores de crecimiento» desaparecieron.

La elongación final de los fémures fue con diferencia la más difícil. Durante la fase de elongación no podía aguantar ningún peso y estaba confinada a una silla de ruedas. Ir de aquella independencia recientemente conseguida a necesitar absolutamente para todo a otros no fue fácil para la adolescente de espíritu libre que yo era. Pero sabía que era por una buena razón . Pasé todo aquel año de instituto recibí clases en casa. Al final, lo positivo superó a aquellas limitaciones físicas y tras seis meses la deformidad de flexión de mi cadera desapareció y yo había crecido otras cinco pulgadas.

Nunca olvidaré la sensación de ponerme de pie junto a uno de mis mejores amigos por primera vez, ojos a la altura de los ojos. O el momento en que me senté en una silla y mis dos pies tocaban el suelo. No se pueden explicar esos momentos con palabras, pero dieron todo el sentido a que yo hubiera decidido someterme al proceso de elongación.

Cuando empecé con las elongaciones sabía que había una gran controversia en torno a ellas. Little People de América consideraba que se trataba de pura estética e insistía en que los que elegían elongarse lo hacían para encajar en la sociedad y que estaba renunciando, en última instancia, a quienes realmente eran. Yo no me mentí al decirme que mi motivación no era ser más alta, encajar o cambiar mi verdadero ser. Mis ojos y mi corazón se posaban en mi futuro. Seguiría siendo Kristen, la niña que nació con enanismo. Nada podría cambiar eso.

Poco a poco, la gente está poniendo menos objeciones a la elongación ósea y creo que es porque los que lo hemos hecho somos siempre abiertos sobre la experiencia. Muchas veces, los padres de talla normal que tienen un niño de talla baja preguntan sobre la elongación ósea porque la quieren para sus hijos. Algo en lo que siempre insisto es en que fui yo quien tomó la decisión de someterme al proceso. Habría sido apoyada por mis padres en todo caso. Esto requiere compromiso por ambas partes, todos estamos juntos en ello. El éxito pesa más que el dolor ocasional y los bajones de ánimo. Es tan importante para quien se va a someter a la elongación estar dispuesto a ello como estar preparado para ello. Entender todo lo que implica. La elongación ósea no es para todo el mundo y está bien así.

Ni en mis más locos sueños podría haber imaginado que la medicina moderna afectara mi vida de esta manera. Sí, soy más alta, proporcionada y recta gracias a este procedimiento. Requirió perseverancia, lágrimas y fuerza. Y durante casi cuatro años entré y salí casi constantemente del hospital. Pero la magnitud de la experiencia en conjunto es casi imposible de describir.

Cuando era pequeña pedía a Dios que al despertarme por la mañana fueran las cosas diferentes. La gente dejaría de pararse por la calle para mirarme como si fuera un objeto ridículo y me aceptarían como la persona que era, no por mi apariencia. Decir que mis ruegos han sido respondidos es decir poco. A lo largo de los años me he cruzado con gente que me ha enseñado valor, fuerza, compasión y cómo quererme por lo que soy. El viaje ha ablandado mi corazón. No sólo no me arrepiento, sino que siento una gran gratitud por las personas y los aprendizajes que esta experiencia me ha regalado.

.

Cuando te enfrentas a tu condición o enfermedad como una discapacidad se convierte en una prisión. Cuando la reconoces como una identidad es una fuente de libertad. Mi nombre es Kristen y soy una mujer con enanismo que se ha sometido a un proceso de elongación ósea. Gracias, Dr. Paley, por usar sus dones para hacerme un poquito más grande por dentro y por fuera.

Kristen
Charleston, Carolina del Sur

Créditos: Paley Institute

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