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.