Vanishing white matter (VWM) is a leukodystrophy caused by recessive gene variants. The disease is characterized by chronic neurologic deterioration with episodes of rapid decline. VWM is rare and likely underdiagnosed, particularly in adults. Currently, only symptomatic care is offered, including measures to prevent stressors that could provoke acute deteriorations. A recent paper by the global VWM consortium, led by Marjo van der Knaap and Prisca Leferink of Amsterdam Neuroscience, has formulated recommendations for enhanced diagnosis, drug trial setup, and patient selection.

Because of the rarity of the disease, a global consortium was established to enable and accelerate therapeutics for VWM. Nine neurologists involved in leukodystrophy patient care and research from eight academic medical centers worldwide assist in the drug development processes and clinical trial design. Clinical trials in VWM are considerably challenging due to low numbers of known patients with VWM, unpredictable disease onset and course, and absence of intermediate biomarkers.

Recently, the VMW consortium, which works closely together with the Industry Alliance Office of Amsterdam Neuroscience, published their first paper together with patients’ associations formulating recommendations for enhanced diagnosis, drug trial setup, and patient selection, based on evaluations of molecular, laboratory, and clinical data. In the paper, the consortium showed that the grim situation is shifting as different molecular targets have been identified, and several drugs are in clinical development. However, efficacy trials are still challenged by the low number of known patients with VWM, variability, and unpredictable disease course for onsets after early childhood.

Some recommendations of the VWM consortium are to increase the diagnostic rate of VWM, develop biomarkers that can be used in therapy trials, share data from all trials with a minimum common set of outcome measures, and more compassionate use of trial drugs for patients not fulfilling the inclusion criteria. They conclude that the opportunity to advance therapy for VWM will depend on the collaboration of patients, clinicians, industries, and regulatory agencies.

Read the publication in the Neurology Genetics Journal: Therapy Trial Design in Vanishing White Matter.

Or find more background information on the website of the global VWM consortium.