MPS I Intrathecal Enzyme Replacement Clinical Trial Information

The Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, California and the University of Minnesota are collaborating on a Study of Intrathecal Enzyme Replacement Therapy for cognitive decline in patients with Mucopolysaccharidosis Type I.

The purpose of this research study is to find out whether giving enzyme replacement therapy with Aldurazyme® as an injection directly into the cerebral spinal fluid (the fluid around the spinal cord and the brain) can stabilize (keep from getting worse) or improve

cognitive decline in patients who have MPS I. The term “cognitive decline” refers to a change for the worse in our ability to think and learn. Difficulty with thinking, memory, language, concentration and decision making are some signs of cognitive decline.

To be eligible for this study, you or your child must be willing and able to comply with the study procedures and meet certain criteria:

• 6 years of age or older
• Diagnosed with MPS Type I
• Show evidence of cognitive decline on a screening evaluation
• Study participants will have:
• Up to 10 treatments given 1-3 months apart over 2 years (treatment group)
• or 4 treatments given 3 months apart beginning at month 12 (control group).
• Physical Examinations (general and neurologic)
• Neuropsychological testing for cognitive decline and MRI of the brain,
• Reimbursement/payment of travel expenses

Additional details about this clinical trial can be found at the ClinicalTrials.gov website,

(www.clinicaltrials.gov ); search under “mucopolysaccharidosis”.

If you are interested in this study or would like more information, please contact:

Dr. Agnes Chen or Dr. Patricia Dickson

Tel: (310) 222-4160 (310) 222-4145

Fax: (310) 782-2999 (310) 782-2999

Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it This e-mail address is being protected from spambots. You need JavaScript enabled to view it

MPS I Intrathecal ERT for Spinal Cord Compression

Enzyme replacement therapy (ERT) has been developed for mucopolysaccharidosis I (MPS I), a lysosomal storage disorder. ERT helps many physical ailments due to the disease, but does not treat the central nervous system, due to inability to cross the blood brain barrier. The purpose of this study is to test delivery of ERT to the spinal fluid via intrathecal injection in patients with MPS I. In this pilot study, recombinant human α-L-iduronidase will be administered intrathecally once per month for four months to individuals age 8 and older with the Hurler-Scheie and Scheie forms of MPS I and spinal cord compression. For questions regarding age, please contact Dr. Dickson.  If successful, intrathecal delivery could represent a practical, straightforward method of treating central nervous system disease due to lysosomal storage.

Primary Outcomes: safety of intrathecal enzyme treatment by blood and spinal fluid tests each month; improvement in neurologic signs related to spinal cord compression, by neurologic examination and Japanese Orthopedic Association Scale each month; improvement in neurologic symptoms related to spinal cord compression, by subjective assessments and independence of functioning scale each month; improvement in mobility, by six-minute walk test each month; improvement in spinal cord compression by MRI imaging and somatosensory evoked potentials at baseline and 4 months; improvement in lysosomal storage by spinal fluid glycosaminoglycan levels at each treatment.  Secondary Outcomes: improvement in spinal fluid pressure, by opening pressure measurements at each intrathecal treatment; improvement in hydrocephalus and other brain lesions by MRI at baseline and 4 months
Expected Total Enrollment:  10

Additional information can be obtained at http://www.clinicaltrials.gov/ct/show/NCT00215527?order=1 or by contacting the Principal Investigator, Dr. Patricia Dickson, 310-222-4145    This e-mail address is being protected from spambots. You need JavaScript enabled to view it

MPS I Intrathecal ERT for Children Being Considered for Transplantation

The University of Minnesota has recently obtained FDA approval for the delivery of Laronidase into the spinal fluid of children with Hurler syndrome being considered for marrow/cord blood transplantation.  The goal of these studies is to decrease the neuropsychologic decline that has been observed in children with Hurler from the time the patients are initially evaluated to the time they are 1 year from transplantation.  The hypothesis is that there is a significant delay in achieving sufficient enzyme levels in the brain following transplantation, and that this may be overcome by giving enzyme into the spinal fluid until this occurs.  Patients with Hurler syndrome that are between 8 and 36 months of age that have not previously received enzyme therapy and are being considered for transplantation at the University of Minnesota are eligible. Patients receiving Laronidase in the spinal fluid will also be on intravenous Laronidase prior to transplant.  The study will involve 4 doses of Laronidase given during a lumbar puncture (LP, or spinal tap) approximately 3 months before transplantation, at the time of admission to the hospital for the transplant, 3 months after the transplant and 6 months after the date of the transplant.  The Principal Investigator of the study is Dr. Paul Orchard, who can be reached at 612-626-2961, or by email at This e-mail address is being protected from spambots. You need JavaScript enabled to view it .  Alternatively, Teresa Kivisto is the nurse coordinator involved with this study, and she can be reached at 612-273-2924, or by email at This e-mail address is being protected from spambots. You need JavaScript enabled to view it . 

MPS II

MPS II Intrathecal Enzyme Replacement Clinical Trial

Shire Human Genetic Therapies is sponsoring a clinical trial at the University of North Carolina at Chapel Hill to learn if direct administration of recombinant enzyme into the fluid around the brain and spinal cord is safe and a possible treatment for children with MPS II with developmental delays.  The principal investigator for the clinical trial “A phase I/II safety and ascending dose ranging study of idursulfase administration via an intrathecal drug delivery device in pediatric patients with MPS II who demonstrate evidence of central nervous system involvement and who are receiving treatment with Elapraise” is Joseph Muenzer, MD, PhD.

Currently there is no approved therapy for treating the brain and spinal cord in patients with the severe form of MPS II.  The goal of this study is to give a new preparation of iduronate-2-sulfatase (idursulfase-IT) directly into the fluid surrounding the brain and spinal cord (intrathecal administration).  The new form of iduronate-2-sulfatase has not been used before in patients with MPS II and is considered investigational.  It has not been approved by the FDA or any other regulatory agency.

This Phase I/II clinical trial is planning to enroll 16 patients with MPS II between the ages of 3 to 8 years with evidence of early neurocognitive decline using an open-label, three-dose trial design.  This clinical trial will initially have both a treatment group (12 study patients) and a control group (4 study patients) with the control group eligible to receive intrathecal enzyme after a six month observational period.  The monthly intrathecal administration of idursulfase-IT will be given using a Port-A-Cath® II Low Profile™ intrathecal implantable access system manufactured by Smiths Medical MD, Inc. (St. Paul, MN) that requires surgical implantation.

To be eligible for the investigational intrathecal enzyme replacement clinical trial, study patients needs to have some developmental delay, but can not be severely impaired, have received and tolerated a minimum of 6 months of weekly intravenous Elapraise and have adequate hearing (with or without hearing aids) to complete developmental assessments.  Patients with MPS II are not eligible if they have a shunt for the treatment of hydrocephalus, have had a cord blood or bone marrow transplant or have other medical conditions that may place the individual at an increased risk during the investigational clinical trial.

If you are interested in obtaining more information about the clinical trial, please contact Dr. Joseph Muenzer (919.966.1447) or the study coordinator, Heather Preiss, RN (919.843.5731) at the University of North Carolina at Chapel Hill, NC.

MPS III

A Phase I/II Safety, Tolerability, Ascending Dose and Dose Frequency Study of Recombinant Human Heparan N-Sulfatase (rhHNS) Intrathecal Administration Via an Intrathecal Drug Delivery Device in Patients With Sanfilippo Syndrome Type A (MPS IIIA)

Shire Human Genetic Therapies (Shire HGT) is developing a sulfamidase enzyme replacement therapy (ERT)rhHNS for patients with MPS IIIA.  rhHNS is being administered into the cerebrospinal fluid (CSF) via a surgically implanted intrathecal drug delivery device (IDDD), because when administered intravenously (IV) it does not cross the blood brain barrier (BBB).

This study is a multicenter, multiple-dose, dose escalation study designed to evaluate the safety, tolerability, and clinical activity of up to 3 dose levels (2 doses [10 and 45mg] monthly and 1 dose [45mg] every other week for 6 months) of rhHNS administered via an IDDD in patients with Sanfilippo syndrome Type A ages greater than or equal to 3 years of age.

The phase I/II clinical trial is planning to enroll 15 patients, beginning June 2010.  The study is expected to be completed March 2012, and the duration of the study for each patient is nine months.

Patients who have completed all study requirements in this study Study HGT-will be invited to participate in an open-label extension study that will be designed to evaluate long term safety and clinical outcomes of intrathecal administration of rhHNS.

The Phase I / II clinical study is being conducted at two sites: Emma Children’s Hospital, Academic Medical Center in The Netherlands by Dr. Frits Wijberg and the St. Mary’s Hospital in Manchester, UK under the direction of Drs. Simon Jones and Ed Wraith.  Click here to read the letter to the Society from Shire with more details about this study.

Additional information about the clinical trial can be obtained at http://clinicaltrials.gov/ct2/show/NCT01155778?term=MPS+III+intrathecal&rank=1 or by contacting Tiffany Crump 484-595-8257, This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Daryll Heron +44 1256 894572, This e-mail address is being protected from spambots. You need JavaScript enabled to view it . 

MPS IV

BioMarin Pharmaceutical Inc. announced on April 29, 3010 positive results for the Phase I/II trial for BMN 110 or N-acetylgalactosamine 6-sulfatase (GALNS), intended for the treatment of the lysosomal storage disorder Mucopolysaccharidosis Type IVA (MPS IVA), or Morquio A Syndrome. The company expects to initiate a pivotal Phase III trial in the fourth quarter of 2010.

The Phase I/II study is designed as an open-label, within-patient dose escalation trial in approximately 20 patients followed by a treatment continuation phase. During the dose escalation phase of the study, subjects receive weekly intravenous infusions of GALNS in three consecutive 12-week dosing intervals: 0.1 mg/kg for twelve weeks, 1.0 mg/kg for twelve weeks and 2.0 mg/kg for twelve weeks. The objectives of the Phase I/II study are to evaluate safety, pharmacokinetics, pharmacodynamics, clinical response to therapy and to identify the optimal dose of GALNS for future studies.

Highlights from the Phase I/II study:

• Endurance improvements with GALNS were consistent with, and in some cases, better than those observed in pivotal studies of approved enzyme replacement therapies.
• Clinically meaningful improvements in two measures of endurance (6-minute walk distance and 3-minute stair climb) were achieved at both 24 weeks and 36 weeks as compared to baseline. (See Table 1 below).
• Clinically meaningful improvements in two measures of pulmonary function (forced vital capacity and maximum voluntary ventilation) were achieved at 36 weeks as compared to baseline. (See Table 1 below).
• Keratan sulfate levels decreased shortly after the initiation of treatment and fell further as the study progressed. (See Table 1 below).
• The frequency and severity of infusion reactions were comparable to those observed with Naglazyme and Aldurazyme.

"We are encouraged that clinically significant improvements in endurance and pulmonary function can be detected with GALNS treatment even in a relatively short study of a heterogeneous population. This gives us confidence that we can design a robust 24 to 36 week Phase III clinical study with a measure of endurance as the primary endpoint and several additional supportive endpoints. We will be working to reach an agreement with regulatory authorities on a powerful and large Phase III trial protocol that minimizes regulatory risk and captures the maximum amount of clinical benefit expeditiously," said Hank Fuchs, M.D., Chief Medical Officer of BioMarin. "We are on track to initiate a Phase III registration-enabling program in the fourth quarter of 2010."

Additional information can be found at www.bmrn.com and through clinicaltrials.gov, http://clinicaltrials.gov/ct2/show/NCT00787995?term=MPS+IV&rank=1.

MPS VII

A gene therapy clinical trial for mucopolysaccharidosis type VII (MPS VII), also known as Sly Syndrome has been put on hold pending additional data.

ML II/III

There currently are no programs in place for developing treatment options for ML II/III