August 2, 2007
RE: MPS IVA (Morquio) Project
Dear ALL Morquio Families and Friends,
We hope that all Morquio families are going well.
First of all, thanks for your great contribution on Morquio Project. We highly appreciate to have all Morquio families join our movement and activity.
Owing to formidable efforts and supports by families, MPS Societies, Morquio Foundations, and supporters, the members in our Morquio Dream Team have now increased to 8 persons (see the last picture of our members). We are sure that we can increase the more activity to promote the Morquio project. Without contribution and appreciation by each individual Morquio family, Societies, and local communities, we could never reach this point. Thanks again for your great help!
We are now still in discussion on the clinical program on Morquio. We expect to have Natural History Program of Morquio prior to the clinical trial. Natural History Program will be held to know more about Morquio A Disease.
Once it is available, we are very happy to announce it. Please kindly wait a little more. Thanks for all the patience.
Brief summary of the Morquio Related issues is as follows:
1. We have successfully finished Morquio family meeting and workshop as well as the fundraising party hosted by Bellassai family and Mary Smith (Seattle, WA: July 1 to 4).
Maurizio Bellassai, Maurizio@bellassai.com Betsy Bellassai, email@example.com Thanks for the formidable efforts for the family.
With Morquio patients (Seattle, WA)
Dinner with Morquio Patients and Families!
Troy Becker Morquio Patient
Mandy & Annie Bellassai Morquio Patients
Tara Creeden Morquio patient
Ian Michael Smith, Morquio patient with Dr. Shunji Tomatsu
The coming events (meet Morquio families!)
A. Reggae for Cure (Sat. August 4th 2007 Belmont, CA)
Hosted by Ariana’s Cure Fund for Morquio
See the attachment!
From Kallas Family
Hello Friends & Family,
Can you all help out Ariana's Cure by posting this on your myspaces, websites, and by sending this to friends and your mailing lists by email. Together let's make this another successful benefit for Morquio research.
George Kallas, President
B. Miracle for Eddie Milwaukee, WI On September 16
"A Miracle for Eddie" is a reality! We have begun the planning for a fundraiser for Morquio Research. It will be on Sunday, September 16th at the American Legion Post. Mark your calendars and come support the research that will stop the progression of Morquio in children.
Host family: Kimminau Family
Contact Jennifer Kimminau at firstname.lastname@example.org.
A Miracle for Eddie
PO Box 207546
West Allis, WI 53227
Carol Ann Foundation: www.morquio.com
(See the attachment)
From Kimminau Family,
Hi Friends and Family,
I am writing to update you on our son Eddie. Eddie was diagnosed with Morquio Syndrome last August. He has had his share of struggles in his short life, but we are hoping that soon those struggles will be lessened. I have attached a brochure that explains what he is going through, what Morquio Syndrome is, and how Brad and I are so hopeful that a treatment will soon be a reality.
Brad and I, along with wonderful family and friends, are planning a fundraiser on September 16th to raise money solely for research to find a treatment for Morquio Syndrome. If you would like to help by donating your time, items for auction, concessions, or a monetary donation, we would be so thankful.
Please take a minute to look over the brochure, check out Eddie's website www.caringbridge.org/visit/eddiek, and feel free to pass this on.
Jeni & Brad KImminau
Join this meeting! Ask the host in details!
Thanks again for your great interest and contribution on Morquio Project. We are very thrilled to meet Morquio families in the next events!
We will have a discussion with an individual family at both family meetings.
The following issues will be presented and discussed.
1. International Morquio A Registry
2. Educational CD for Morquio
3. Murine models for MPS IVA
4. ERT of MPS IVA
5. Question and Answer
We are very pleased to meet as many as Morquio families through the meeting. We are very happy to make a presentation of our Morquio Project to date and to discuss with each individual family. We enclosed the meeting brochure at Milwaukee, WI.
We have the similar questions on Morquio A syndrome as follows:
Q. 12 The pregnant woman who has a baby (fetus) affected by Morquio will have a higher tendency of miscarriage or not.
Ans. Since we do not have any such data scientifically, we can not conclude any on this.
However, one thing is true that Morquio kids are born with normal height and weight from our registry data (this is scientific: over 350 patients data). Therefore, it is very hard to tell that you are affected by Morquio at birth. Again, Morquio kinds have normal stature at birth!
Overall, the most miscarriage may not be related to Morquio and that it will be just coincidential or by accident.
Of course, we have to learn this issue from Morquio families more statistically: how often does the pregnant woman who has a baby affected Morquio have miscarriage? Such incidence is higher or not compared with normal population.
We hope that we can conclude this issue in the near future through the registry program.
Q1. How can I tell my child is severe or mild? My affected child is similar to other Morquio kids?
Ans. I enclose the Morquio Registry paper here which over 300 patients have kindly contributed to through the questionnaire. You may see some similarity and difference with your kids. Clinical severity is sometimes difficult to say exactly: at least we must see the information of growth chart, DNA analysis, enzyme assay, and keratan sulfate level.
We are very close to finish “Growth Chart for Morquio Patients” with age. Once it is available, you may compare your kid with other Morquio kids. We will inform you!
Please keep the growth chart record as many as possible since at birth. We will also have more registry and biochemical data to be published. Thanks for your great contribution!
Q2. How important to measure keratan sulfate (KS)?
Ans. KS is sort of sugar chain. Morquio patients can not digest KS since one of the enzymes to digest KS is missing in the body. Therefore, KS is accumulated in the body, especially, in the cartilage (bone) and eye cornea. The stored KS will destroy the cartilage layer (growth plate). Because of that, Morquio patients have a lot of signs and symptoms related to the bone. It is quite important to know how much KS is elevated in the body (urine and blood). KS level is age-dependent and it is the highest when the kids grow. There are two major methods to measure KS quantitively: one is to use antibody against KS and the other one is to use the very modern instrument (so-called, tandem mass spectrometry). Tandem mass spectrometry is very sensitive method and can measure KS even in the mouse.
Q3. When do we have to consider the surgical operation?
Ans. It is hard to predict when the appropriate time is. However, the most important operation is “cervical fusion” to protect against the unstable neck. From the registry data, around 30% of patients who had operations may require it. The average age is around 9 years. Please ask the experienced doctor about the indication.
Q4. Is there any animal model of Morquio? How will you confirm whether any treatment is effective or not prior to human patients?
Ans. So far except human patients we only have three different types of Morquio model mice. No other animal models are known. Generally, we try to treat the animal model prior to human patients. Since there is no animal model except mice, we use Morquio mouse model at this point. Our mouse model has a unique feature to produce inactive human Morquio enzyme. Therefore, we can treat this mouse model continuously for a long term without any problem. Generally, if we infuse the human enzyme into the mouse body, the human enzyme will be neutralized since the mouse recognizes it as a foreign body. We are treating Morquio mice by several different treatment methods to see the effectiveness. The most important issue is how to reach the bone especially, growth plate since the growth plate region does not have vessels.
Q5. We have glaucoma (or strabismus) on the eyes. Is that related to Morquio disease or not?
Ans. According to the textbook or common sense among doctors, we could say it is unrelated. However, the recent registry data or the information from the patient may change such concept. As Morquio patients live longer, these eye symptoms may be more popular. Therefore, we need more detail analysis before the definite conclusion of relation between Morquio disease and these eye issues.
Again, there is no statistical analysis made on these subjects. None of doctors and scientists do not know the clear answer. Since we have a schedule to the natural history program in a large scale from many Morquio patients, we may have more precise answer.
Q6. The growth hormone will work on Morquio patient?
Ans. It will be unlikely to have a huge benefit by using the growth hormone since Morquio patients have sufficient growth hormone in the body. The fundamental issue of Morquio disease is caused by destruction of the growth plate with the accumulation of keratan sulfate in the cartilage cells. Therefore, we have to clear such storage material. Some patients have used the growth hormone in the past. However, till now, we have not noticed the huge benefits have occurred. Of course, there is still argument on when or how to treat the patient by the growth hormone since only several patients have used it so far.
Q7. Why is it so difficult to develop of Morquio A drug?
Ans. We have several reasons.
- It is a very rare disease (1 out of 200,000-300,000 births). Therefore, only 1200 patients are suffering from Morquio A disease in developed countries. Therefore it is not so easy for the big company to have an interest to develop the drug.
- It is systemic bone disease. It is a challenge to improve the bone lesions compared to other visceral organs like liver, spleen, kidney etc.
- Enzyme deficient in Morquio patients is not easy to be purified since the enzyme is unstable.
In addition, we have to need the detailed preclinical tests (mouse, monkey, rat etc.) to go forward to the clinical trial.
Q8. How much will enzyme replacement therapy or other treatment like gene therapy work on Morquio patients?
Ans. This is a very critical question but also it is very difficult to answer at this moment. Since we have never treated Morquio patients, we can not predict how much effective. Especially, many factors must be considered: age, clinical severity, the extent of storage material, current clinical situation, condition of the bone deformity etc. The effectiveness will vary by individual patient. Some patients will get more benefits but others will get less benefit. According to the other types of MPS patients treated by enzyme replacement therapy, to improve bone lesions, it will take time. Early treatment at an early stage will provide a more benefit. We are treating Morquio A mouse model at a different age currently. Gene therapy is still at quite an early stage on Morquio A, therefore, we can not predict any at this moment. We are currently under way of some other new treatments on Morquio mouse models. We hope that we can answer more clearly.
Q9. Morquio patients can get the child? The child is also affected by Morquio?
Ans. Yes. Morquio patients can have own child. However, special consideration must be done for woman Morquio patients since the lung capacity and abdominal capacity are very small. Generally, woman Morquio patients need Cesarean section at the delivery. The child is not affected by Morquio A unless the partner is a carrier or Morquio A patient.
Q10. Why do Morquio patients have hypermobile joint (loose ligament)? And is there any help to put the wrist bands?
Ans. There are two possibilities: one is because of small bones on the hands and wrists. The other possibility is the connective tissue and ligaments surrounding wrists are severely affected. The wrist bands could be helpful to sustain the grip power. The drawing, writing, and the computer typing can help to maintain the function. All are supportive treatment. Indication of surgical procedures remains uncertain and its consequence is not clear since very few patients have received the operation so far.
Q11. We do not know about Morquio disease. How can we get the information?
Ans. First please ask the expert of your country or region and your each individual national MPS Society. International Morquio Organization will also send the educational CD without any charge. Please ask the available language as well since we have several languages for educational CD.
Q12. What kinds of rehabilitation do we have to take? Any recommendation?
Ans. This is very important since the appropriate rehabilitation will maintain your skills and strength as well as physical activity. Generally, we recommend physiotherapy (swimming), diet therapy (refrain from overweight), fine motor skills (computer, any music instrument, drawing, writing), and walking if possible. Ultimately, each individual patient must find the most appropriate one by him or herself since signs and symptoms are different.
We are now summarizing the rehabilitation methods. Hopefully, we can put the methods in next version of educational CD.
Q. 13 How can we relieve the pain?
Ans. There is no universal method to relieve the pain. Also it depends upon how severe, how often, where, worsening or not etc. We are now summarizing the pain killer methods. Once it is done, we will inform it ASAP.
Scientific papers may be difficult to be understood, but if you have any further specific question, please let me know.
President Mary Smith
The Carol Ann Foundation & The International Morquio Organization
8164 W. Circulo De Los Morteros Tuscon, Arizona 85743
Dr. Shunji Tomatsu
Shunji Tomatsu MD. PhD
Educational CD for Morquio (Japanese version)
We have educational CD for Morquio. If you want to know Morquio disease, it will be good educational slides. Please ask The Carol Ann Foundation & International Morquio Organization for this CD. It is completely free of charge! We have this CD for several languages including English, Arabic, Japanese, German, Polish, Spanish etc.
Morquio Project has been supported by grants from the following non-profit organizations (alphabetically):
Ariana’s Cure Fund for Morquio
Austrian MPS Society
Austrian Research Society for Mucopolysaccharidoses and Related Diseases
Care For Carly Foundation
German MPS Society
International Morquio Organization (Carol Ann Foundation)
Italian MPS Society
Jacob Randall Foundation
National MPS Society
Spanish MPS Society
Thanks for all supports and appreciation on Morquio Project. We also thank for cooperation to join the International Morquio Family and each National Morquio Registry Program for each Society.
We are expanding the activity! Please support our activity!
Morquio Dream Team July 17, 2007
Please kindly look at the following web sites to know the variety of activity by
Address for Morquio Foundations:
The Carol Ann Foundation & International Morquio Organization
President Mary Smith
The International Morquio Organization
8164 W. Circulo De Los Morteros Tuscon, Arizona 85743
Telephone: 520-850-7264 Fax 520-744-2535
The Bennett Foundation
President Steve Waters
714 Richmond Street
Brunswick, Georgia 31520
(912) 222-1363 or (912) 262-9525
Jacob Randall Foundation for Morquio
President Renee Little
12125 Lexington Park Dr. #208
Tampa, FL 33626
Telephone: 813- 731-8274
Ariana’s Cure Fund for Morquio
President George Kallas
San Francisco CA
Danette Baker Website for Morquio Group
Annabelle Bozarth Website
Website: www.caringbridge.org (under the name
BELLE) Go to Journal
Sarah Van Orden Website
Ruthann Van Orden
Care For Carly Foundation
A Miracle for Eddie
Isabella Burton web site
Sota Isomoto Website (Japanese)
Please let me know if you have any own Morquio web site!!!
Tomatsu Shunji MD PhD
Professor and Director, Skeletal Dysplasia Lab
Pediatric Orthopedic Surgery
ARB 331 Alfred I. dupont Institute Hospital for Children
1600 Rockland Rd.,Wilmington, DE. 19899-0269