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Research 101

Gene TherAPY

You may have heard about gene therapy in the news, and researchers have long believed gene therapy held great promise for MLD patients. MLD was one of the first diseases to be treated with gene therapy

What is gene therapy?

Gene therapy has been around for decades, but it was in 2009 when a researcher named Alessandra Biffi attempted to treat a child with MLD using gene therapy at the Telethon Institute in Milan, Italy  There are many forms of gene therapy, but Dr. Biffi used a treatment called lentiviral hematopoietic  stem cell gene therapy. Dr. Biffi and her colleagues believed that they could replace the broken ARSA gene mutation that causes MLD with a working copy of the gene to start producing the arylsulfatase A enzyme. Dr. Biffi hoped the treatment would  slow down the disease’s progression. Much to Dr. Biffi and her colleague’s amazement, this pioneering gene therapy exceeded all expectations and the first children had MRIs that appeared normal two years after treatment.  


What is even more remarkable is how gene therapy works. To replace a broken gene, researchers need a vehicle to transport the corrected gene to our cells. That vehicle is the HIV virus, stripped of its harmful properties. You see, viruses are really good at getting inside and telling them what to do. HIV is a very efficient virus. And researchers hoped they would be able to  “infect” a patient’s cells with a repaired copy of the ARSA gene they needed to be healthy.   


The treatment shows great potential but, sadly, cannot be used on all patients. Moreover, since most MLD patients are diagnosed after they have symptoms, gene therapy is not as effective. One of the most important efforts of Cure MLD will be newborn screening. Identifying children at birth who will develop MLD will be crucial to defeating MLD.


You see, gene therapy works by slamming the brakes on a disease to halt MLD’s progression. It cannot repair the damage to the brain or central nervous system.


While the results of the research have been impressive, some patients treated with MLD can walk, others use walkers or wheelchairs. Moreover, it is not clear how long the therapy will stop the disease’s progression. But, the research on gene therapy for MLD has offered new hope for our community.  However, as gene therapy becomes more efficient, safe, and fast-acting, we expect to see new treatments available to a wider range of patients, possibly even symptomatic ones.


Watch this video featuring Dr. Biffi discussing her work to develop a gene therapy.

To learn more about the Orchard Therapeutics’ gene therapy trial, please have your doctor contact Dr. Francesca Fumagalli at Please note the gene therapy clinical trial may require travel to Milan, Italy. You can watch this video featuring the Price family and hear about their remarkable journey.

At the end of 2020, Orchard Therapeutics' MLD gene therapy, Libmeldy, was approved for commercial use in the European Union (EU). They have also begun the process of bringing gene therapy to the United States. Just recently, a pre-approval access site was opened up in Minnesota. Additionally, a late-juvenile arm of the trial in Italy is now actively recruiting (you can find the eligibility criteria here). Learn more about Orchard Therapeutics' updates by visiting their website here.

I would like information about treatment options and clinical trials.

What is enzyme replacement therapy?

As of April 2024, the Embolden Study trial run by Takeda Pharmaceuticals (TAK-611) is closed and no longer accepting new participants. The trial initially closed recruitment in January 2021 after reaching the right amount of participants  .

While enzyme replacement therapies (ERT) have shown promise in treating a number of lysosomal storage disorders like Pompe, Gaucher, Batten and Fabry diseases, the clinical trial did not meet its primary or secondary endpoints. After numerous conversations with families, patient advocacy groups, and clinicians, Takeda has decided to extend its ERT trial for existing, enrolled patients. The trial is still closed to all other families. 


Enzyme replacement therapy (ERT) is used to treat genetic disorders just like MLD where there is an insufficient amount of enzyme produced. Enzyme replacement therapies work to supplement an enzyme deficiency via regular infusions in a small port. For MLD, that infusion occurred weekly. For the ERT, a functional enzyme is produced in the laboratory by cells that have been genetically modified. The cells are then harvested and the enzyme is purified before being given to the patient. 

Embolden Study Image (Cure MLD)

You are not alone, please contact us and we will have a family ambassador contact you.

We will also send you and your loved one a special care package that includes Loie’s Disease, a children’s book to explain leukodystrophy to children, and the “Living with Leukodystrophy” medical resource guide.

Lorie's Disease Book Cover (Cure MLD)
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