InnoSuisse Consortium «The NeurOphthalmoscope: Early diagnosis of brain diseases.»
In the frame of the InnoSuisse project consortium, together with partners such as «Best start-up team of the year»- company machineMD, CSEM (Centre Suisse d’Electronique et de Microtechnique), and Helbling Technik Bern AG, we thrive to develop a cutting-edge Virtual Reality Tool NeurOphthalmoscope or “NEOS” that will enable a high-quality, multimodal neuro-ophthalmological and neuro-otological examination. With this novel tool, we aim to improve the diagnosis and management of rare diseases.
A Longitudinal Study of Neurological Functions, Associated Brain Connectivity, and Metabolic Markers in Young Patients with Classic Galactosemia
One of our current projects focuses on the rare metabolic disease classical galactosemia (CG), characterised by the inability to metabolize galactose. Due to the high galactose content in mammalian milk, newborns with this disorder present with acute intoxication syndrome, which can become life threatening. Thus, in Switzerland, it is part of the neonatal screening. Upon diagnosis, a galactose-restricted diet is immediately introduced and recommended for life. Despite this early intervention, individuals with CG commonly develop long-term complications particularly in the brain. To date, a comprehensive understanding of the onset and the development of CNS-related symptoms in CG is still lacking. Together with the Department of Pediatrics, namely Dr. Matthias Gautschi, Division Metabolism, and Prof. Regula Everts-Brekenfeld, Division Neuropsychology, and the Ph.D. candidate Anja Maria Vossenkaul we aim to characterize the neuropsychological, neurological, and metabolic phenotypes in children and adult population suffering classical galactosemia.
SV-WMD & Dizziness
Another main area of interest is vertigo and dizziness. Vertigo and dizziness are the second most common neurological symptom in neurology. In the elderly population, one of the most common reasons for falling is dizziness. The greatest number of fatal falls concerns adults 65 years and older. According to the World Health Organization, as of January 2018, falls are the second leading cause of accidental or unintentional injury deaths worldwide. Supported by the Baasch-Medicus stipend for protected-research time, I aim to shed light on the cerebral small-vessel, white matter disease (SV-WMT) and its link to dizziness. By the broad instrument-based battery in our vertigo lab, we aim to relate the deficits in the balance system and the severity of SV-WMD, associating them with the subjectively perceived dizziness. Optimizing of the cardiovascular risk factors early in life, and focused balance training should have an impact on the morbidity and mortality in this vulnerable elderly population and improve the management of the elderly at risk of falling.
ALL in NPC
Multinational, randomized, placebo-controlled, double-blinded, cross-over Phase III clinical trial to assess safety and efficacy of ALL (IB1001) versus Placebo for the treatment of NPC.
Acetyl-DL-leucine (ADLL) has been used for more than 6 decades in France to treat acute vertiginous episodes. The clinical experience has shown that it is a well-tolerated drug without serious adverse events. In 2015, our pilot case-series study in patients with Niemann-Pick disease, type C ( NPC) indicated the possible positive symptomatic effects on cerebellar ataxia, but also other modalities of this rare debilitating disease. The further basic research studies, and clinical trials demonstrated the positive effects of acetyl-L-leucine (ALL) in lysosomal storage disorders, suggesting not only symptomatic, but also disease-modifying effects. I am the principal investigator of the only study site in Switzerland for the multinational, randomized, placebo-controlled, double-blinded, cross-over Phase III study that will assess the safety and efficacy of ALL (IB1001) versus Placebo for the treatment of children >4 years of age and adults with NPC. The development of this re-purposed drug for lysosomal storage diseases is a model example of the translational and back-translational research enabled by the close cooperation with the lab of Prof. Frances Platt, University of Oxford.
Bremova-Ertl T, Claassen J, Foltan T, Gissen P, Hahn A, Hassan A, Hennig A, Jones S, Kolnikova M, Martakis K, Ramaswami U, Sharma R, Schneider S Efficacy and Safety of N-acetyl-L-leucine in Niemann-Pick disease type C. J Neurol 2021 Aug 13;1-12. doi: 10.1007/s00415-021-10717-0. Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C - PubMed (nih.gov)
Kaya E, Smith D, Smith C, Morris L, Bremova-Ertl T, Cortina-Borja M, Fineran P, Morten K, Poulton J, Spencer J, Strupp M and Platt F Acetyl-leucine slows disease progression in lysosomal storage disorders. Brain Communications, Volume 3, Issue 1, 2021, fcaa148, https://doi.org/10.1093/braincomms/fcaa148. LINK: Acetyl-leucine slows disease progression in lysosomal storage disorders - PubMed (nih.gov)
Churchill GC, Strupp M, Factor C, Bremova-Ertl T, Factor M, Patterson MC, Platt FM, Galione A. Acetylation turns leucine into a drug by membrane transporter switching. Sci Rep. 2021 Aug 4;11(1):15812. doi: 10.1038/s41598-021-95255-5. Acetylation turns leucine into a drug by membrane transporter switching - PubMed (nih.gov)
Bremova T, Malinová V, Amraoui Y, Mengel E, Reinke J, Kolníková M, Strupp M. Acetyl-dl-leucine in Niemann-Pick type C: A case series. Neurology. 2015 Oct 20;85(16):1368-75. doi: 10.1212/WNL.0000000000002041. Acetyl-dl-leucine in Niemann-Pick type C: A case series - PubMed (nih.gov)