We are pleased to announce that Shanice Beerepoot, currently doing a PhD at the Center for Children with White Matter Disorders, Amsterdam University Medical Centre, the Netherlands (ERN-RND member) has been awarded an EJP RD fellowship, congratulations!
Why the study collaborators think that this study is important
Pre- and early-symptomatic MLD patients can be treated with an allogenic hematopoietic stem cell transplantation. The treatment rationale is that hematopoietic stem cells from a donor can cross the blood-brain and blood-nerve barrier, and differentiate into macrophages that produce ASA to correct the enzyme deficiency. However, in the majority of MLD patients this treatment has primarily effects on the brain white matter whereas the peripheral nerves show no or limited treatment response. Consequently, the central nervous system functions remain stable and survival increases, but the peripheral neuropathy often worsens during follow-up. The latter is reflected by an ongoing decline in nerve conduction velocity and deterioration of clinical symptoms in approximately 75% of the patients.
Peripheral neuropathy has a major impact on the morbidity of untreated and treated MLD patients by causing e.g. neuropathic pain, foot deformities and neurogenic bladder disturbances. Still, scientific data about the etiology, course and prognostic markers of peripheral neuropathy in MLD patients are lacking. In our own clinical experience, we observed that there is much variation in the severity and progression of peripheral neuropathy between MLD patients, both in the untreated and treated patient groups. Besides, case reports on nerve enlargement raise questions about time dependent alterations of peripheral nerve morphology and its etiologic implications. Results of this study will increase knowledge on the course of peripheral neuropathy in MLD patients and might help to predict peripheral neuropathy progression over time in untreated and treated MLD patients, improving patient counselling and treatment decision making. In addition, we experience that characterizing progressive peripheral neuropathy in HCT treated MLD patients is challenging, especially when the disease is stabilized in the brain. Questions of the neurologists are whether the progressive peripheral neuropathy is linked to disease progression and MLD subtype or an acquired immune mediated disease, such as Graft-versus-host disease or chronic inflammatory demyelinating polyneuropathy. More information on the trend of peripheral neuropathy over time after treatment might help to fill in this current knowledge gap, and might help the neurologists during follow-up of these patients.
The EJP RD, from which ERN-RND is a participant, offers many opportunities to visit colleagues across Europe to foster research collaborations and enhance knowledge sharing so please keep an eye on current and upcoming calls for funding here.