The University Medical Center (UMC) Utrecht, Netherlands, has announced that it has enrolled its first patient in a new study to identify biomarkers of amyotrophic lateral sclerosis (ALS), in collaboration with VectorY Therapeutics.

Findings from the longitudinal study could support the development of VectorY’s lead programme, VTx-002, a targeted TDP-43 treatment for ALS.

Affecting more than 200,000 people worldwide, ALS is a progressive neurological disorder that affects motor neurons, the nerve cells in the brain and spinal cord, impacting muscle movement and breathing.

Aiming to enrol 70 ALS patients in the Netherlands, the study will identify blood or cerebrospinal fluid (CSF) biomarkers of ALS patients to help improve diagnosis, monitor disease progression, improve the design of future clinical studies and provide insights into ALS pathogenesis to help support the development of new therapeutics.

All blood and CSF samples will be collected, while multiple potential biomarkers will be identified and tested, including TDP-43-related biomarkers, which are indicative of the pathogenic processes leading to motor neuron degeneration.

TDP-43 is an RNA/DNA-binding protein that plays a key role in the regulation of RNA processing in the nucleus and cytoplasm.

Currently in preclinical development, VectorY’s VTx-002 is a vectorised antibody that selectively clears misfolded and aggregated TDP-43 from the cytoplasm of neuronal cells, restoring the essential function of TDP-43 in the nucleus, to preserve neuronal cell function and health in ALS.

Researchers at the Francis Crick Institute, University College London (UCL) and AstraZeneca (AZ) have revealed why targeted treatment for non-small cell lung cancer (NSCLC) fails for some cancer patients.

The study demonstrated how lung cancer cells with two genetic mutations are more likely to double their genome, withstanding treatment and developing resistance.  Around 85% of all lung cancer cases are NSCLC, the most common type of lung cancer found in patients who have never smoked.

A common genetic mutation found in NSCLC is in the epidermal growth factor receptor gene (EGFR), which accelerates cancer cell growth and is found in up to 15% of NSCLC cases in the UK.

After re-analysing data from the trial of AZ’s EGFR inhibitor, Tagrisso (osimertinib) – among patients with either EGFR-only or EGFR and p53 mutations – researchers found that tumours got smaller in response to treatment in patients with just the EGFR mutations. Meanwhile, some tumours had grown in patients with both mutations, providing evidence of rapid drug resistance.

Researchers then investigated why tumours may be more prone to drug resistance using mouse models with both the EGFR and p53 mutations.

Results showed that mice with resistant tumours had far more cancer cells that doubled their genome, giving them extra copies of all of their chromosomes.