Research Faces of MLD

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San Rafaelle Gene Therapy

Gene Therapy Clinical Trail - Now Recruiting!

A gene therapy clinical trial is scheduled to start recruiting in late March 2010. The protocol uses the patients own genetically modified hematopoietic stem cells to increase ARSA product 0-15x the normal rate. This super-production is offset by the reduced number of cells that typically cross the blood brain barrier.

Gene therapy is based on the principle that every illness caused by gene defect can be cured by inserting, through viral vectors, a functional copy of the gene in the sick cells of the patient. In the case of the MLD, it is problematic to insert the functional gene in the sick cells of the central and peripheral nervous system for the inaccessibility of these organs. It is, however, possible, by using appropriate gene transfer systems, to correct in a stable way hematopoietic cells that can transport then the functional enzyme to the affected nervous system.

The proposed protocol is similar to the historical transplantation of hematopoietic cells from healthy donors, but is hoped to be a less risky and more effective alternative thanks to the use of autologous, the patient's own cells,

Trial Center
The study will take place in Milano (Milan) Italy. 8 MLD patients are being recruited. The study is a Phase I / I with a requirement from the Italian authorities to show efficacy.

The recruitment of the patients is international. All costs of patients and families participating in the study will be paid by HSR-TIGET.

Inclusion Criteria
• Late infantile MLD in pre-symptomatic phase (usually identified because of an older affected sibling)
• Early juvenile MLD in pre-symptomatic phase or within the first 6 months from the onset of the symptoms.
• (Presumably) no prior therapies

Protocol Summary
• Bone marrow extraction from the patient of the patient
• Isolation of the stem cells to be submitted to gene transfer
• Manipulation of the stem cells ARSA production capability with the lentiviral vector
• Minimal patient conditioning with Busulfan (GVHD is greatly reduced due to re-implantation of patient's own cells)
• Re-infusion of the manipulated stem cells

Primary efficacy end points are an improvement or stability in the motor performances assessed by the "Gross Motor Function Measure, GMFM" 24 months after the treatment, in comparison to the scores obtained in a cohort of untreated patients of peer age, and a significant increase of the ARSA activity in the patients' hematopoietic cells measured 24 months after the treatment, in comparison to the pre-treatment values.

Follow Up
The follow-up post-treatment will be performed at regular intervals fro 3 years with 5 more years of formal post-trial study.

Principal Investigators:
• Dr. Alessandra Biffi, Project Leader at HSR-TIGET & Staff Pediatrician in Pediatric Immunohematology and Bone Marrow Transplant Unit at HSR.+39-02-2643-4678/4681 FAX:+39-02-2643-4668
• Dr. Maria Sessa, Project Leader at HSR-TIGET & Staff Neurologist at HSR (also a member of the MLD Foundation's Medical & Scientific Advisory Board). +39-02-2643-2755 FAX:+39-02-26432951

HSR-TIGET ... San Raffaele Institute
HSR-TIGET was funded in 1995 as joint- venture among the Scientific Institute San Raffaele and the Telethon Foundation for the research and treatment of rare genetic diseases. Main goal of the Institute is to be a center of excellence in all the phases of the research from basic to clinical gene and cellular therapy, from the experimentation of new therapeutic strategies in the animal models of disease up to their clinical testing in the patients.

Quick Links

March 4, 2010 - Trial Document from San Raffaele

Dr. Sessa Video overview of the Gene Therapy research from a 2009 MLD Family Conference™

Video interview of Dr. Biffi discussing the Clinical Trial (March 201) ... coming soon.


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