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Voice of the Patient Report

Metachromatic Leukodystrophy (MLD)
Voice of the Patient Report

Key MLD EL-PFDD Meeting Insights  


1. Metachromatic leukodystrophy, or MLD, is a rare and progressive neurologic disease with devastating impacts. Most patients with this lysosomal storage disorder live less than a decade after diagnosis. Some families include multiple affected family members.


2. Unfortunately, most MLD families endure long diagnostic odysseys, with an MLD diagnosis made long after the appearance of initial symptoms which prevents access to viable therapies. Earlier forms of MLD usually present first as mobility challenges, and progress rapidly from onset. Later presenting forms of MLD are less predictable, generally first presenting with cognitive and behavioral changes which may be initially hard to recognize as MLD.


3. Most MLD patients experience devastating symptoms including regression, a loss of communication, impaired mobility and balance challenges, feeding and GI motility, and cognitive and behavioral challenges. Additional MLD symptoms include muscle tone issues, muscle cramps, seizures, pain and irritability, respiratory issues, vision issues, incontinence, anxiety, depression, fatigue, gallbladder abnormalities, fine motor issues, drooling, temperature regulation, neuropathy, renal issues, and scoliosis.


4. Earlier diagnosis is necessary. Newborn screening for MLD will ensure that children with MLD can be identified presymptomatically and be eligible for life-saving gene therapy, among other potentially curative therapies. For all other patients, the time from the first symptoms to diagnosis must be shortened so that patients will gain more benefit from earlier therapeutic intervention.


5. MLD profoundly impacts quality of life for patients and their entire families. Patients are completely dependent on their caregivers, and most cannot be left unattended. Younger patients are at risk of aspirating and choking. Older patients are socially isolated and a risk to themselves. Caregivers worry that their loved one will be unable to breathe and will die prematurely, that their loved one will experience uncontrolled pain, and that communication and responsiveness will decrease.


6. Disease modifying therapies for MLD now exist and when delivered early, are potentially life-changing. Gene therapies and enzyme-replacement therapies now offer hope; however, only presymptomatic and minimally symptomatic patients are eligible. Financial and geographic barriers result in treatment inequity. During the EL-PFDD meeting, many parents compared the lives of siblings who received therapy with those who had not.


7. There is an urgent need for treatments for MLD patients across the spectrum of disease, especially for those who are already symptomatic, including adult patients. Currently, patients rely on a very large number of different treatments and medications to control and manage symptoms and for comfort at the end of life. These palliative care options are not curative and will not slow or stop the progression of MLD.


8. Leveraging existing data and using novel clinical trial designs will allow more MLD patients to be treated. Experts recommended methods for measuring meaningful improvement in systematic patients such as non-comparator trials with historical patient data or using patients as their own controls.  

 I would like to speak to the Ambassador Outreach Program Coordinator

MLD Externally Led Patient-Focused Drug Development Meeting Additional Patient Comments 

The Metachromatic Leukodystrophy (MLD) Externally-Led Patient Focused Drug Development (EL-PFDD) meeting held on October 21, 2022 was organized and hosted by a collaboration of MLD patient advocacy groups and researchers including Cure MLD, the Calliope Joy Foundation, MLD Foundation, United Leukodystrophy Foundation and the Global Leukodystrophy Initiative.  


The meeting represented an important opportunity for the MLD community to share patient, family and caregiver perspectives on the challenges and unmeet treatment needs of those who live with MLD every day. The patient and caregiver perspectives gathered from the October 21, 2021 EL-PFDD meeting are summarized in an accompanying Voice of the Patient report, To ensure that as many voices as possible were heard, an online comment submission portal was open for one week before and four weeks after the MLD ELPFDD meeting. Comments that were submitted through the online comment submission portal are presented in this document, and selected comments are included in the main body of the Voice of the Patient report.  


Respondents are identified by their first name only. Comments were sorted by MLD subtype and treatment approach (gene therapy, enzyme replacement therapy [ERT], bone marrow transplant [BMT] and no therapies). Comments were edited only slightly for spelling and punctuation. Comments that did not address the Meeting Discussion Questions from Appendix 3 of the Voice of the Patient report were not included.


Late infantile MLD



Victoria, mother of two children living with late infantile MLD, two-year-old Oliver who received gene therapy and six-year-old Adeline who did not


• “I am pleased with the outcome of Oliver’s gene therapy. However, Oliver is delayed and shows signs of MLD. I wish I had known more about the possible outcomes of gene therapy. The good and bad.”

• “Addi is completely dependent on us for all of her care, in addition she also suffers from acute respiratory failure.”

• “Newborn screening and a treatment to completely prevent symptoms.”  


Les, father of two sons with late infantile MLD, Cathal, who passed away at age six and Ciarán, who received gene therapy and is now six 

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