The Academic Medical Center in Amsterdam and Saint Mary's Hospital in Manchester (UK) are both looking for suitable candidates for a trial with heparan N-sulfatase, the enzyme replacement therapy for patients with Sanfilippo syndrome (Mucopolysaccharidosis type IIIA), developed by Shire.
More information about the inclusion and exclusion criteria and contact information here:
http://www.clinicaltrials.gov/ct2/show/NCT01155778?term=MPS+III+A&rank=1.
Mucopolysaccharidosis IVa (MPS IVA, Morquio A disease) is an inherited lysosomal storage disorder that features skeletal chondrodysplasia caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS).
Human GALNS was bioengineered with the N-terminus extended by the hexaglutamate sequence (E6) to improve targeting to bone (E6-GALNS).
We initially assessed blood clearance and tissue distribution. Next, to assess the effectiveness of storage clearance and reversal of pathological phenotype, a dose of 250 U/g of enzyme was given weekly to Morquio A mice (adults: 12 or 24 weeks, newborn: 8 weeks). Sulfatase modifier factor 1 (SUMF1) was co-transfected to activate the enzyme fully. The E6-GALNS tagged enzyme had markedly prolonged clearance from circulation, giving over 20 times exposure time in blood, compared to untagged enzyme.
The tagged enzyme was retained longer in bone, with residual enzyme activity demonstrable at 48 hours after infusion. The pathological findings in adult mice treated with tagged enzyme showed substantial clearance of the storage materials in bone, bone marrow, and heart valves, especially after 24 weekly infusions. Mice treated from the newborn period showed marked reduction of storage materials in tissues investigated.
These findings indicate the feasibility of using tagged enzyme to enhance delivery and pathological effectiveness in Morquio A mice.
source: http://www.ncbi.nlm.nih.gov/pubmed/20332769?dopt=Abstract
Lentigen Corporation, a biotechnology company specializing in the development and manufacture of lentiviral gene delivery technologies, announced that it has received a National Institutes of Health (NIH) small business technology transfer (STTR) grant for a program on “Lentiviral Gene Therapy for Mucopolysaccharidosis.” In this program, Lentigen will collaborate with Dr. R. Scott McIvor Professor, Department of Genetics, Cell Biology and Development, and Dr. Walter Low, Professor, Departments of Neurosurgery and Physiology at the University of Minnesota, Minneapolis, MN.
The goal of this program is to evaluate the feasibility of using lentiviral vectors to restore the missing gene in patient’s cells and return the cells back to the patient. The specific research that will be conducted under this grant will use a mouse model of MPS II created in the laboratory of Dr. Joseph Muenzer, University of North Carolina, to establish and test conditions for introduction of the correcting gene and its effectiveness when reintroduced into the animals.
more info: http://www.lentigen.com
While the Dutch were in the streets celebrating the Queen’s birthday yesterday, Thai authorities arrested a man for insulting the Thai royal family on Facebook.
Wipas Raksakulthai (age 37) said he didn’t insult the king. The police didn’t say what he wrote.
Insulting the king and his family is one of the worst crimes and often results in long prison sentences. The high aged Bhumibol is accorded God-like status among the Thai people.
I just wonder how any man or family allows oneself to be revered like God on earth. I hate to tell you this, but gods don’t poop and pee like men. This particular family even carries a MPS disorder gene. I don’t think gods are ever in need for diapers, medicine or feeding tubes!
For this reason alone Raksakulthai should be released.
King Bhumibol should use his God-given position to raise MPS awareness rather than having people worship him.
Just my opinion… dunno…
Miguel, desperate because of the silence of the Chilean government, has ended his hunger strike and went on a quest to find treatment for his son Kemuel.
Kemuel has Hunter syndrome (MPS II), but Chile does not want pay for Elaprase, a drug needed to treat him and the other 13 patients in that country.
Miguel and Kemuel set of on a journey to find treatment somewhere in South America. On April 24th they left Arica (Chile). Having gone through Bolivia and Argentina, their journey took them to Porto Alegre in Brazil; the most important research center for MPS in the area.
Miguel and Kemuel crossing the Bermejo river that seperates Bolivia from Argentina
Tucuman, Argentina
the hospital in Porto Alegra, Brazil
Please, pray for this brave family. Follow their footsteps on La Ruta de Kemuel.
Rumour has it that Shire is planning an ERT clinical trial for Sanfilippo syndrome (MPS III) in June 2010 in the Netherlands (and Manchester, England).
I’ve written before about Miguel and his hunger strike (see below).
Miguel writes today:
Ayer fue un dÃa muy difÃcil… hoy es un dÃa demasiado pesado para llevar… no se qué pasará mañana… creo que necesito ayuda.
(Yesterday was a very difficult day … today is a day too heavy to carry … do not know what will happen tomorrow … I think I need help).
You are in our prayers Miguel!
It is possible to clearly identify the gender of a fetus after only 7 weeks of pregnancy through a blood test drawn from the pregnant woman. Until now reliable testing was only possible after 11 weeks with amniocentesis, with risk of a miscarriage.
A gender test is useful for detecting congenital gender-related disorders.
Researchers from Sanquin in Amsterdam published the test in Obstretics an Gynecology.
source: nrc.next
New investigation results, ‘Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulphate storing mucopolysaccharidoses,’ are detailed in a study published in European Journal of Human Genetics. According to recent research published in the European Journal of Human Genetics, "Neurological pathology is characteristic of the mucopolysaccharidoses (MPSs) that store heparan sulphate (HS) glycosaminoglycan (gag) and has been proven to be refractory to systemic therapies. Substrate deprivation therapy (SDT) using general inhibitors of gag synthesis improves neurological function in mouse models of MPS, but is not specific to an MPS type."
"We have investigated RNA interference (RNAi) as a method of targeting SDT to the HS synthesising enzymes, EXTL2 and EXTL3. Multiple shRNA molecules specific to EXTL2 or EXTL3 were designed and validated in a reporter gene assay, with four out of six shRNA constructs reducing expression by over 90%. The three EXTL2-specific shRNA constructs reduced endogenous target gene expression by 68, 32 and 65%, and decreased gag synthesis by 46, 50 and 27%. One EXTL3-specific shRNA construct reduced endogenous target gene expression by 14% and gag synthesis by 39%. Lysosomal gag levels in MPS IIIA and MPS I fibroblasts were also reduced by EXTL2 and EXTL3-specific shRNA. Incorporation of shRNAs into a lentiviral expression system reduced gene expression, and one EXTL2-specific shRNA reduced gag synthesis," wrote X. Kaidonis and colleagues.
The researchers concluded: "These results indicate that deprivation therapy through shRNA-mediated RNAi has potential as a therapy for HS-storing MPSs."
