Publications by authors named "J H Weishaupt"
Genetic alterations in the ERCC4 gene typically cause Xeroderma pigmentosum and other nucleotide excision repair disorders. Neurologic symptoms are present in some of these patients. In rare cases, ERCC4-mutations can manifest with prominent neurologic symptoms.
View Article and Find Full Text PDFAmyotrophic lateral sclerosis (ALS) is a fatal, adult-onset disease marked by a progressive degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Death in most patients usually occurs within 2-4 years after symptoms onset. Despite promising progress in delineating underlying mechanisms, such as disturbed proteostasis, DNA/RNA metabolism, splicing or proper nucleocytoplasmic shuttling, there are no effective therapies for the vast majority of cases.
View Article and Find Full Text PDFBackground: Fasudil is a small molecule inhibitor of Rho-associated kinase (ROCK) and is approved for the treatment of subarachnoid haemorrhage. In preclinical studies, fasudil has been shown to attenuate neurodegeneration, modulate neuroinflammation, and foster axonal regeneration. We aimed to investigate the safety, tolerability, and efficacy of fasudil in patients with amyotrophic lateral sclerosis.
View Article and Find Full Text PDFgene screening in ALS - frequency of mutations, patients' attitudes to genetic information and transition to tofersen treatment in a multi-center program.
Amyotroph Lateral Scler Frontotemporal Degener
September 2024
Article Synopsis
- A study was conducted at 11 ALS centers in Germany from October 2021 to February 2024 to evaluate the frequency of pathogenic gene variants in ALS patients and their transition to an expanded access program for tofersen treatment.
- Out of 1935 patients screened, 48.8% chose to be informed about genetic variants related to tofersen, revealing that 1.8% had (likely) pathogenic variants, 0.9% had other pathogenic variants, and 7.0% showed hexanucleotide repeat expansion.
- The transition to tofersen treatment from genetic testing averaged 94 days, with a notable 74.0% of patients with certain variants opting for the therapy, highlighting the importance of comprehensive
Article Synopsis
- The introduction of the antisense oligonucleotide tofersen for treating ALS caused by SOD1 mutations emphasizes the need to clarify the impact of over 230 SOD1 variants, particularly the debated p.D91A variant common in Europe.
- A study involving 11 ALS patients treated with tofersen for up to 16 months shows that it significantly reduces serum neurofilament light chain (sNfL) levels, which are linked to ALS progression, in both homozygous and heterozygous SOD1 patients.
- These findings support the role of mono- and bi-allelic SOD1 variants as relevant targets for treatment, offering a new perspective for assessing causality based on biomarker responses in clinical