Rare Diseases – Current And Upcoming Treatments

Dr. Ram begins by outlining the clinical course of MLD, a rare lysosomal storage disorder caused by arylsulfatase A deficiency, which leads to sulfatide accumulation and progressive demyelination. He reviews the rapid deterioration seen in untreated cases—particularly in late-infantile and early juvenile forms—and emphasizes the critical importance of identifying patients early. Gene therapy, specifically atidarsagene autotemcel (Libmeldy), has shown transformative outcomes when delivered in the presymptomatic stage. It involves harvesting the patient’s hematopoietic stem cells, modifying them to express functional ARSA, and reinfusing them post-conditioning. Clinical trial data demonstrate significant preservation of cognitive and motor function in appropriately selected patients.

However, only a minority of children referred for treatment meet eligibility criteria. This underscores the importance of early recognition, ideally through newborn screening or sibling testing. Dr. Ram emphasizes the need for clinicians to remain alert to subtle early signs and act quickly to initiate enzyme and genetic testing.

Dr. del Toro complements the discussion by focusing on the management of patients who are ineligible for gene therapy due to advanced symptoms. Using a case study of twin boys with progressive MLD, she highlights the need for holistic, multidisciplinary care. This includes spasticity and pain management, respiratory and nutritional support, sleep interventions, and attention to quality of life for both patient and family. She also discusses the frequent occurrence of gallbladder complications in MLD, recommending regular ultrasound monitoring.

Looking forward, the speakers discuss emerging research areas such as substrate reduction therapy, enzyme replacement approaches (including intrathecal delivery), and newer gene editing technologies. While these options are not yet widely available, they represent hope for broader patient populations in the future.

The session concludes with a strong call for investment in newborn screening programs, family education, and international collaboration to expand access to effective treatments. While gene therapy has reshaped the treatment landscape for early-diagnosed patients, supportive care remains essential for the majority of those affected by MLD today.