Beyond Achondroplasia

Growing together with Clara

May 8, 2018
by inesp.alves
3 Comments

Study on achondroplasia – request for participation in the USA

The Brod Group, a health outcomes research, and consulting firm are currently conducting an international study of pediatric achondroplasia.

Purpose of the study

To get a better understanding of the experiences and daily life of children and adolescents with achondroplasia, as well as the experiences of parents who have children with achondroplasia.

The study findings

Will be used to helping identify important outcomes to consider in future studies of achondroplasia and the results may also be a useful tool to address misconceptions of achondroplasia.

In this document, ACH Study Advertisement you can find additional study details.

Participants

This will be an international study and researchers are now looking for participants living in the U.S.A.

  • children with achondroplasia with ages between 9 and 11 years old
  • parents with achondroplasia that also have children with achondroplasia under 18 years of age  (one interview per family)

How will the study be conducted?

  • In a 1-hour telephone interview or a 2-hours focus group (location is to be determined but possibly in New York City)
  • All data will be kept confidential, and no individual will be identified in the study results
  • There is a $125 honorarium for participating in a focus group and a $75 honorarium for participating in a telephone interview

If you are interested in participating, adding value to this research with your personal real-life knowledge on achondroplasia, please contact Jane Beck, Senior Research Associate with The Brod Group:

e-mail: jane@thebrodgroup.net

telephone: (415) 317-3987

May 4, 2018
by inesp.alves
0 comments

The soluble FGFR3, Therachon´s TA- 46, may prevent early onset of obesity in achondroplasia

Obesity and metabolism are important topics related to achondroplasia but rarely discussed.

Developed especially during childhood, obesity is a common complication associated with achondroplasia, affecting more than 50% of people with this condition. The extra weight exacerbates many other complications associated with achondroplasia, such as lumbar lordosis and obstructive sleep apnea, and may play a role in the increased cardiovascular-related death observed in people with achondroplasia, making it a relevant medical complication in the management of this disease [1].

This complication is generally accepted as a risk factor for a number of complications, such as cardiovascular disease, diabetes, and hypercholesterolemia (excess cholesterol in the blood) in the general population. Although cardiovascular disease is higher in people with achondroplasia than in the general population [2], a few case studies suggested that achondroplasia related obesity doesn’t cause alterations in insulin and cholesterol levels [3-5].
This study was firstly presented in the 2017 International Skeletal Dysplasia Society meeting (report of ISDS 2017 here) by Dr. Celine Saint-Laurent, from Elvire Gouze research team, and the team demonstrated the existence of metabolic alterations in achondroplastic mouse model and in children with achondroplasia. Also, they showed how that the soluble FGFR3 (sFGFR3) therapy could revert these metabolic alterations in this mouse model.

To understand what happens to children witachondroplasiaia, the research team performed a longitudinal retrospective study. So what is this? 

In a longitudinal study, subjects are followed over time with continuous or repeated monitoring of risk factors or health outcomes, or both [6]. And retrospective is when a study looks backwards and examines exposures to suspected risk or protection factors in relation to an outcome that is established at the start of the study [7].

They also evaluated anthropometric measures: body mass index – BMI, height, weight, etc, and blood parameter values were recorded and compared between children of 3 age groups: 0-3, 4-8 and 9-18 years old. After this, the researchers discovered that glucose (blood sugar) and insulin levels (a hormone made by the pancreas that allows your body to use glucose from carbohydrates in the food consumed for energy or to store glucose for future use. Insulin helps keeps your blood sugar level from getting too high (hyperglycemia) or too low (hypoglycemia) [8], were within normal, but these children had a tendency to have low cholesterol and triglyceride levels (fat), which is markedly different from what happens in obesity not associated with achondroplasia.

Key points:

1. The fact that obesity in achondroplasia is different at a metabolic level from obesity in the general population and that it is a relevant medical complication makes it a good indicator for the efficacy of a medication for achondroplasia.

2. Although sFGFR3 has already shown to increase body length and decrease mortality in an achondroplasia mouse model, the researchers also measured how this drug would affect these metabolic disturbances in the same mouse model and demonstrated that the soluble FGFR3 prevented the atypical abdominal obesity observed in untreated mice and that it normalized some of the blood parameters.

 

Image 2. Regions of interest (ROI) for obesity in children with achondroplasia and Android:gynoid fat ratio measurement in the three age groups. Credits: Saint-Laurent C, Garcia S et al., 2018. Android fat distribution describes the distribution of human adipose tissue in the trunk and upper body while Gynoid fat refers to the body fat that forms around the hips, breasts and thighs [10]

Background:
Achondroplasia is a rare genetic disease is characterized by abnormal bone development and early obesity. While the bone aspect of the disease has been thoroughly studied, early obesity affecting approximately 50% of them during childhood has been somewhat neglected. It nevertheless represents a major health problem in these patients and is associated with life-threatening complications including increased risk of cardiovascular pathologies. We have thus decided to study obesity in patients and to use the mouse model to evaluate if soluble FGFR3 therapy, an innovative treatment approach for achondroplasia, could also impact the development of this significant complication.
Methods and findings:
To achieve this, we have first fully characterized the metabolic deregulations in these patients by conducting a longitudinal retrospective study, in children with achondroplasia Anthropometric, densitometric measures as well as several blood parameters were recorded and compared between three age groups ranging from [0±3], [4±8] and [9±18] years old. Our results show unexpected results with the development of an atypical obesity
with preferential fat deposition in the abdomen that is remarkably not associated with classical complications of obesity such as diabetes or hypercholesterolemia. Because it is not associated with diabetes, the atypical obesity has not been studied in the past even though it is recognized as a real problem in these patients. These results were validated in a murine model of achondroplasia (Fgfr3ach/+) where similar visceral adiposity was observed. Unexpected alterations in glucose metabolism were highlighted during a high-fat diet. Glucose, insulin or lipid levels remained low, without the development of diabetes. Very interestingly, in achondroplasia mice treated with soluble FGFR3 during the growth period (from D3 to
D22), the development of these metabolic deregulations was prevented in adult animals(between 4 and 14 weeks of age). The lean-over-fat tissues ratio was restored and glucose metabolism showed normal levels. Treating Fgfr3ach/+ mice with soluble FGFR3 during the growth period, prevented the development of these metabolic deregulations in adult animals and restored lean-over-fat tissues ratio as well as glucose metabolism in adult animals.

Conclusions:This study demonstrates that

  1. achondroplasia patients develop an atypical obesity with preferential abdominal obesity not associated with classical complications.
  2. These results suggest that achondroplasia induces an uncommon metabolism of energy, directly linked to the FGFR3 mutation.
  3. These data strongly suggest that this common complication of achondroplasia should be included in the clinical management of patients.
  4. In this context, sFGFR3 proved to be a promising treatment for achondroplasia by normalizing the biology at different levels, not only restoring bone growth but also preventing the atypical visceral obesity and some metabolic deregulations.

We look forward in seeing how this compound, the soluble FGFR3 (the same as TA-46 from Therachon) will be effective in children with achondroplasia when the company presents phase 2 clinical trial results.

Sources
  1. Unger, S., L. Bonafé, and E. Gouze, Current Care and Investigational Therapies in Achondroplasia. Current Osteoporosis Reports, 2017. 15(2): p. 53-60. 
  2. Wynn, J., et al., Mortality in achondroplasia study: A 42-year follow-up. American Journal of Medical Genetics Part A, 2007. 143A(21): p. 2502-2511. 
  3. Collipp PJ, Sharma RK, Thomas J, Maddaiah VT, Chen SY. Abnormal glucose tolerance in children with achondroplasia. Am J Dis Child. 1972; 124(5):682±5.
  4. Pirgon O, Atabek ME, Sert A. Achondroplasia associated with metabolic syndrome: patient report. J Paediatr Child Health. 2008; 44(10):602±4.
  5. Alatzoglou KS, Hindmarsh PC, Brain C, Torpiano J, Dattani MT. Acanthosis nigricans and insulin sensitivity in patients with achondroplasia and hypochodroplasia due to FGFR3 mutations. J Clin Endocrinol Metab. 2009; 94(10):3959±63.
  6. https://www.bmj.com/about-bmj/resources-readers/publications/epidemiology-uninitiated/7-longitudinal-studies
  7. https://www.statsdirect.com/help/basics/prospective.htm
  8. https://www.endocrineweb.com/conditions/type-1-diabetes/what-insulin
  9. Saint-Laurent C, Garcia S et al.Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia, PLos One, 2018 Apr 13;13(4):e0195876.
  10. https://en.wikipedia.org/wiki/Gynoid_fat_distribution

March 4, 2018
by inesp.alves
3 Comments

5th Nordic Skeletal Dysplasia Symposium – full session dedicated to achondroplasia

The 5th Nordic Skeletal Dysplasia Symposium will be held in Copenhagen, on March 8-9, 2018.

As stated in the Welcome note of this symposium “Skeletal dysplasias are rare diseases and the annual symposium is important to share medical knowledge with colleagues in different countries. We hope to attract all medical professionals who are working in – or are interested in – the field of skeletal dysplasias. This includes both caregivers, clinicians, scientist, and students“.

On the day 2 of the event, a full session will be dedicated to achondroplasia, on the following topics:

13.30-14.30 Management and follow-up of achondroplasia, Irwing M/Osmund D
14.30-15.00 Cervical spine compression/instability: diagnoses, signs and symptoms, Borbjerg T
15.00-15.15 Achondroplasia: mechanical axis considerations. Orthosis – true or false, Hindsø K
15.15-15.30 Finnish quiz with focus on achondroplasia three-five questions, Valta H

We will try to gather and share some information that will be presented at this symposium.

 

March 2, 2018
by inesp.alves
1 Comment

FDA Advisory Committee Meeting on Achondroplasia – Call for patients input

On March 22, 2018, FDA, the US Food & Drug Administration, will conduct a public advisory committee meeting on achondroplasia. The purpose of this meeting to discuss the major objectives of a phase 3 drug development program indicated for the treatment of children with achondroplasia.

FDA values patient perspective on the development of pharmaceutical treatments for achondroplasia and this meeting presents individuals with achondroplasia and their families a valuable opportunity to provide FDA with input on important topics. These topics include the types of clinical trial endpoints that would have a clinically meaningful impact on patients’ functional or psychological well-being and other considerations on the design of clinical trials involving people with achondroplasia.

The meeting’s open public session will take place on March 22, 2018, from 10:30 a.m. to 5:30 p.m. at our location in Silver Spring, MD, just outside of Washington, DC). Individuals, families, and others (patient organizations) may provide testimony in person at this meeting’s open public comment. Anyone interested in providing public comment at the meeting should register with  Marieann.Brill@fda.hhs.gov by March 7.

There are a limited number of speaking slots. In addition, individuals, families, and others can submit a written comment on the topic of achondroplasia and development of potential treatments to the public docket. Additional details can be found in the federal register notice of the meeting.

FDA is seeking to collect a rich and diverse set of patient perspectives on this topic.  We have developed a flyer, attached, with information relevant to this meeting and encourage you to disseminate it to any individuals or groups who may be interested in this meeting.

Preview of the information flyer. To read the flyer in full, click on the following link: AchondroplasiaAC

FDA link to the announcement

 

Beyond achondroplasia will participate in this call for contribution by sending a written comment.

The information here provided was kindly shared by Blake Bannister, Decision Support and Analysis Team, Center for Drug Evaluation and Research, FDA     

February 14, 2018
by inesp.alves
2 Comments

Therachon starts phase 1 clinical trial with TA-46 for achondroplasia

Therachon announced today, 14 February 2018, the beginning of Phase 1 for the clinical trial with TA-46 for achondroplasia.

This trial will take place in The Netherlands, with 70 adult healthy volunteers and it will be:

  • randomized – A study in which the participants are divided by chance into separate groups that compare different treatments or other interventions. Using the chance to divide people into groups means that the groups will be similar and that the effects of the treatments they receive can be compared more fairly. At the time of the trial, it is not known which treatment is best. Pubmed health
  • placebo-controlled – Studies of new drugs often compare the effects of an investigational drug with the effects of a placebo. The reason for using a placebo control is that the benefits of taking medications are not always due to the drug itself. These benefits are called “placebo effects.” An example is when an investigator’s enthusiasm about a new medication sometimes influences the patient’s response. In a double-blind, placebo-controlled research design, the doctors, nurses working directly with patients, and participants themselves involved in the study, will not know which group patients are in. PsychCentral
  • double-blind trial – is a trial where neither the researchers or patients/participants know what they are getting (the drug or the placebo). The computer gives each patient a code number. And the code numbers are then allocated to the treatment groups. Cancer Research UK

The number of participants vary significantly, depending on the study and if teh new medicine is for a more common condition or a rare condition. Credits: Global Medical Institutes

 

The trial is designed to evaluate the safety, tolerability and pharmacokinetics of single and multiple ascending doses of TA-46.

Luca Santarelli, Therachon´s CEO said that this is “an important milestone for the company,”.

Beyond Achondroplasia has published more information about TA-46 previously (read the first article). The company has high expectations that Ta-46 may show significant therapeutic impact in achondroplasia as may improve anatomical proportions and prevent complications related to achondroplasia, that start to occur in early life phases.

Next steps

Is important to know the timelines for this phase 1 trial, namely the duration of this trial as also the results of safety, tolerability and mechanism of the drug in these healthy volunteers and then, after positive results, know the expected dates of the beginning of phase 2, with children with achondroplasia.

How is expected TA-46 to work?

TA-46 acts as a ligand trap can reduce the superactivation of the mutated receptor FGFR3 (that is overworking in achondroplasia, which reduces the multiplication and development of chondrocytes, that the cells that give origin at the growth plate level, to the bone formation).

TA-46 is being developed as a weekly subcutaneous drug for children and adolescents living with the disease.

And this investigational therapy has received Orphan Drug Designation from the European Medicines Agency (EMA) on the 27th March 2017 and the U.S. Food and Drug Administration (FDA).

You can check Therachon´s press release here

January 24, 2018
by inesp.alves
0 comments

Short videos about the work of Medicines Regulators and the path of new medicines

This is a short videos series from EMA, the European Medicines Agency, about new medicines reaching the market and also about the works of regulators, EMA and FDA, which is focused on protecting patients and to approve the best possible new medicines.

December 31, 2017
by inesp.alves
3 Comments

The TransCon CNP for achondroplasia – Ascendis Pharma publications

Ascendis Pharma, a company funded in 2007, applies the TransCon technology which combines a prodrug with a sustained-release technology. This way, the company can offer products with a predictable and sustained release of an unmodified parent drug.

Before heading for the publications the company released in 2017 in selected events, is important to explain some concepts.

What is a prodrug?

A prodrug is an inactive medication or compound (the same as having no action), and after being administrated, it is converted within the body (metabolized) into a pharmacologic active drug.

Prodrugs undergo an enzymatic and/or chemical transformation in vivo (inside the body) to release the active drug: the parent drug, which can then exert the desired pharmacological effect. In both drug discovery and development, prodrugs have become an established tool for improving several properties of active agents: physicochemical, biopharmaceutical or pharmacokinetic.1

Example of a prodrug. Credits: www.clayton.edu

During 2017 Ascendis Pharma released relevant information on the TransCon CNP. Through selected publications, the company shows high expectations on the efficacy of TransCon CNP in improving the quality of life in achondroplasia and reducing complications. In the company website it can be read the following:

Our preclinical studies of TransCon CNP have been encouraging. Continuous exposure to TransCon CNP has been found in preclinical studies to be more efficacious at inducing skeletal growth compared to once-daily injections. In preclinical safety studies, a low Cmax due to slow release of CNP has been shown to improve hemodynamic tolerability. And, the half-life extension observed confirms the potential of convenient weekly dosing in patients with achondroplasia. Additionally, preclinical data suggest a trend toward bone growth associated with TransCon CNPBuilding on these positive results, Ascendis Pharma plans to submit an Investigational New Drug Application for TransCon CNP in the fourth quarter of 2017. Ascendis pharma

What is the Cmax?

Is the maximum concentration of the drug that is measured in the plasma after one dose administration. 2 The concentration of a drug is the abundance of a compound divided by the total volume of a mixture. The following image gives a simple example how to reach the concentration value of a mixture.

Credits: www.fao.org

So, once the TransCon CNP shows a low Cmax, this avoids side effects in the body after the administration of CNP, namely the reduction of blood pressure and an increase of heart rate has shown by other CNP (as BMN-111).

And what is the plasma?

Is the clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma.3 Blood is composed of blood cells suspended in blood plasma, that can be separated by centrifugation (a process used to separate substances that as mixed together).

 

What is the half-life of a drug?

Is the time that takes for the plasma concentration or the amount of drug in the body to be reduced by 50%. 4

So due to an increased half-life of the TransCon CNP, the company sees the potential of having one administration per week of the drug instead of a daily administration.

 

Structural Optimization of TransCon CNP – Development of a Sustained-Release Prodrug of CNP for Achondroplasia

 

The TransCon technology. Credits: Ascendis Pharma

The reduced drop in the blood pressure after Vosoritide and TransCon CNP administration. A preclinical study conducted in monkeys.  Credits: Ascendis Pharma

Main conclusions

  1. The TransCon CNP prodrug has minimal binding to the NPR-B and NPR-C receptors and improved NEP stability in vitro compared to unmodified CNP.
  2. In vivo TransCon CNP demonstrated the desired half-life extension without adverse hemodynamic effects.
  3. These data support clinical development for weekly dosing and suggest TransCon CNP may be a safe and efficacious option for children with ACH. Ascendis Pharma

TransCon CNP, a sustained-release prodrug of C-type natriuretic peptide, prevents premature synchondroses closure in an achondroplasia mouse model

The reduction of the ossification of the areas around the foramen magnum, the synchondroses (IOSA). Credits: Ascendis Pharma

Main conclusions:

  1. In a murine model of ACH, TransCon CNP prevented the closure of synchondroses and resulted in an improvement in foramen magnum and skull shape, suggesting normalization of the overall skull contour.
  2. These results suggest that the early administration of TransCon CNP may alleviate the risk of foramen magnum stenosis that leads to some of the most serious clinical complications of ACH. Ascendis Pharma

Pharmacokinetics and Cardiovascular Assessment of TransCon CNP, a Sustained-Release C-type Natriuretic Peptide Prodrug, for the Treatment of Achondroplasia

Main conclusion:

  1. Continuous exposure to CNP showed better efficacy and CV tolerability than intermittent, daily injections.
  2. TransCon CNP exhibited a substantially longer half-life in cynomolgus monkeys compared to daily CNP analogs, supporting once-weekly dosing in humans
  3. TransCon CNP showed no adverse hemodynamic effects in cynomolgus monkeys or mice at doses exceeding the expected therapeutic dose
  4. TransCon CNP may improve efficacy and safety over daily administered CNP. Ascendis Pharma

TransCon CNP, a Sustained-Release Prodrug of C-Type Natriuretic Peptide, exerts Positive Effects on Bone in Juvenile Cynomolgus Monkeys and in a Mouse Model of Achondroplasia

TransCon CNP administration to Fgfr3Y367C/+ mice from birth to day 15 increased the naso-anal length and bone length (femur; blue arrows, tibia; red arrows). Credits: Ascendis Pharma

Main conclusions:

  1. In young healthy monkeys, once weekly TransCon CNP increased long bone growth in a dose-dependent fashion.
  2. In a murine model of ACH, TransCon CNP improved growth plate architecture and improved phenotypical features.
  3. These data support further development of TransCon CNP as a potential therapy for ACH, providing efficacious CNP levels with weekly administration. Ascendis Pharma

 

Bibliography

1. Rautio J et al, 2008, Prodrugs: design and clinical applications.

2. Science Direct – Cmax (pharmacology)

3. Pubmed Health – Blood Plasma

4. UNIL-Université de Lausanne

December 10, 2017
by inesp.alves
16 Comments

Update on BioMarin´s Achondroplasia Clinical Development Program

BioMarin Pharmaceutical sent to patient organizations an update of the clinical development program for BMN-111. The current status of the achondroplasia clinical programme is described in the document below.
BioMarin’s investigational therapy for achondroplasia, BMN 111, is currently under investigation and has not been approved for use in any country.

Study 111-301

This trial is a phase 3 placebo-controlled trial with BMN-111, includes children from 5 to 17 years of age and approximately 110 participants globally. In this trial, participants are randomly selected to be included in the placebo group or in the drug group.

Outcomes of study 111-301

The primary outcome of the trial is to evaluate a change in the rate of growth or change in height. Secondary outcomes include measurements of health through evaluating health-related quality of life scores, other
associated symptoms, sleep quality as well as major illnesses and surgeries.

Duration

This trial lasts for 52 weeks and participants will have to have to complete a minimum of 6 months in the
observational trial (111-901) before they can be selected for the Phase 3 (111-301) trial.
Participants on placebo can receive the investigational therapy, or the BMN-111, after the 1 year trial period is
complete.

Study 111-501

BioMarin is preparing a new study, the 111-501, on the Lifetime Impact of Achondroplasia Study in Europe (LIAISE) is an observational study (so, no drug will be included) looking at the impact on quality of life, healthcare resource use, clinical, socioeconomic and psychosocial state of individuals living with achondroplasia.

This study is recruiting up to 300 participants between 5 and 70 years of age and will be opening in the following countries between now and early 2018: Germany, Spain, Italy, Sweden, and Denmark. Participation in the

study will include a 5-year review of historical clinical data as well as data obtained using questionnaires.

Read the full document here:

BioMarin ACH clinical development program Nov 2017

October 23, 2017
by inesp.alves
2 Comments

The International Society of Skeletal Dysplasia 2017 meeting report

The International Skeletal Dysplasia Society meeting was held in Bruges between the 20th and 23rd September 2017, with the presence of world-renowned geneticists and clinicians with interest in skeletal dysplasias; also some pharmaceutical companies and patients representatives from all around the world were present.

The companies that were present and that are currently developing medicines for achondroplasia were, by alphabetic order: Ascendis Pharma, BioMarin, and Therachon.

ALPE Foundation has a report of this meeting, where the most relevant information is shared.

To add some clarification on the concepts regarding the Meclozine representation by Hiroshi Kitoh, that presented “Oral administration of meclozine for the treatment of short stature in achondroplasia”

 

His team observed that cutting-off the FGFR3 signaling in-vitro promoted (produced) longitudinal bone growth in transgenic ACH mice (mice that were genetically changed to be born with the ACH mutation). The team has been investigating which is the optimal dose of meclozine for the treatment of short stature in ACH for further clinical application in children.

In vitro - In vitro (Latin for "within the glass") refers to the technique
of performing a given procedure in a controlled environment outside of a 
living organism. Many experiments in cellular biology are conducted outside 
of organisms or cells. One of the weaknesses of in vitro experiments is 
that they fail to replicate the precise cellular conditions of an organism. 
In mpkb.org
FGFR3 ach mouse – Mouse models are currently available for genetic 
research and include thousands of unique inbred strains and genetically 
engineered mutants.  In Genome.gov.
FGFR3 ach mouse model is a mutant strain developed for mice to be born
with the achondroplasia mutation, to conduct scientific studies.

For this study, the team administered orally 1, 2 or 20 mg/kg/ day of meclozine to 7-day-old FGFR3 ach mice for 10 days. The body lengths were measured during the treatment periods and at the end of the treatment, the mice were subjected to micro-computed tomography (micro-CT) scans for calculating the bone length and bone volume.

The pharmacokinetic analyses demonstrated that peak drug concentration (Cmax) of 2 mg/kg of meclozine to mice was similar to those of 25 mg/body to human, which is a clinical usage for anti-motion-sickness. The body lengths of FGFR3 ach mice were increased by oral administration of 1 or 2 mg/kg/day of meclozine and the bone volume and trabecular bone quality were improved by meclozine treatment. Treatment of 20 mg/kg/day of meclozine, however, showed no positive effects on bone growth of mutant mice.

Pharmacokinetics: Pharmacokinetics is the study of drug absorption, 
distribution, metabolism, and excretion. A fundamental concept in 
pharmacokinetics is drug clearance, that is, elimination of drugs
from the body. In Principles of Pharmacokinetics
Micro-computed tomography: Enables a non-invasive inspection to 
screen anatomical changes in small animals. Once the dose received
by the small animal can be a critical concern in the research, the 
advantages of micro-CT include high resolution, high sensitivity 
to bone and lung, short scan time and cost-effectiveness. 
In Li H et al., 2008

Kitoh finished saying that they confirmed a preclinical proof of concept for applying meclozine for the treatment of short stature in ACH, although toxicity and adverse events associated with long-term administration of this drug should be examined. Also, the team is aiming to start a phase 1 clinical trial in Nagoya, Japan in children with ACH, between the end of 2017 and beginning of 2018. The study design is still not disclosed.

 

Metabolic studies on Achondroplasia

But one of the most relevant moments during ISDS was a study presented by Celine Saint-Laurent, a young researcher working in Elvire Gouze´s team in Nice, France (and in collaboration with Therachon). In her presentation, Celine showed that there is a link between the FGFR3 mutation and the metabolic complications related to achondroplasia.

Prior to this study in a mouse model with ACH, Celine firstly conducted a retrospective longitudinal study in children and adolescents with achondroplasia carrying the most frequent mutation of achondroplasia: the G380R FGFR3 mutation. Anthropometric, densitometric measures and several blood parameters were recorded from birth onward during follow up visits and compared between three age groups ranging from [0-3], [4-8] and [9-18] years old.

Celine’s study confirmed that there are metabolic disturbances in achondroplasia patients, that are unexpectedly not associated with classical obesity complications. Indeed, the data gathered showed that while patients with achondroplasia usually develop abdominal obesity, this does not correlate with an increase of typical risk factors of obesity such as high glucose, insulin or lipid levels and that they do not appear to develop diabetes.

In the mouse model study, Celine injected the mice with Flag-soluble FGFR3 (sFGFR3) during the mice growth period and could confirm that the bone growth was restored and the metabolic deregulations were corrected with the administration of soluble FGFR3. The researchers concluded that sFGFR3 proved to be a promising treatment for achondroplasia by restoring bone growth and also by preventing the metabolic deregulations and the development of obesity.

 

Anthropometric measurements: are used to assess the size, shape and 
composition of the human body. Some common methods used to gather 
these measurements are BMI, waist-to-hip ratio, skin-fold
test and bioelectrical impedance.

 

 

October 20, 2017
by inesp.alves
0 comments

Recruitment in clinical trials

The following document, shared by BioMarin in September 2017, is a clarification on the ongoing clinical trials for achondroplasia and was released for associations and families:

BioMarin Achondroplasia Programme Update 20Sept17

It is important to mention that families interested in having their children enrolled in BioMarin ongoing observational study (111-901) and interventional clinical trial (111-301), have to contact the centers that are conducting the clinical trial driectly, listed here.

Pharmaceutical companies DO NOT recruit patients for clinical trials. The companies, such as BioMarin, select the clinical centers (hospitals) in which their trial will take place and is the trial coordinator of that clinical center (usually a chief clinician), that recruits patients and who must be contacted for recruitment.

Translate »