MSCA Postdoc fellow opportunity – Amyotrophic lateral sclerosis (ALS)

Background:

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with limited therapeutic options and an urgent unmet clinical need. Cryptic splicing of ATG4B, a key regulator of autophagy, is present in approximately 97% of ALS patients, making it a highly attractive therapeutic target. We have developed a first-in-class peptide-conjugated phosphorodiamidate morpholino oligomer (peptide-PMO) that potentially restores correct ATG4B splicing and autophagic function.

This technology, protected by a joint patent with the University of Oxford, represents the first peptide-PMO platform specifically designed for central nervous system (CNS) delivery and has the potential to overcome one of the major limitations of current antisense therapies: the need for frequent intrathecal administration.

What we offer:

Next-Generation Peptide-PMO Therapeutics for Restoring Autophagy in ALS: From Target Validation to Clinical Translation.

This fellowship will advance both the therapeutic candidate and the underlying delivery platform through an integrated translational research programme. Using preclinical ALS models and human iPSC-derived motor neurons, the project will characterize pharmacokinetics, pharmacodynamics, tissue persistence, target engagement and duration of action, establishing the basis for extended dosing intervals.

Functional studies will determine the capacity of the therapy to restore autophagic activity, improve motor neuron function and rescue disease-associated molecular and cellular phenotypes, while generating robust preclinical evidence to support future clinical translation.

Beyond developing a therapeutic candidate for ALS, the project will establish a versatile platform for CNS-targeted splice-switching therapies with potential applications in other TDP-43 proteinopathies, including frontotemporal lobar degeneration (FTLD) and Alzheimer's disease. By integrating RNA therapeutics, disease biology, pharmacology and technology transfer, the fellowship will accelerate the translation of an innovative patented technology towards clinical development while generating broadly applicable knowledge for next-generation oligonucleotide medicines.

Due to the strong links between the hosting research group and Oxford University, secondments in England can be proposed during the duration of the postdoctoral fellowship.

Objectives

1. Establish the pharmacokinetic and pharmacodynamic profile of a first-in-class CNS-targeted peptide-PMO targeting ATG4B splicing.Determine biodistribution, tissue persistence, target engagement and duration of splice correction in preclinical ALS models to define the relationship between exposure, efficacy and dosing frequency.

2. Evaluate the therapeutic efficacy and mechanism of action of ATG4B splice correction in ALS.Assess the ability of the lead peptide-PMO to restore autophagic function, improve motor performance and rescue molecular and pathological hallmarks of disease in vivo.

3. Validate therapeutic activity in human iPSC-derived motor neurons.Determine whether ATG4B splice correction restores autophagic homeostasis and improves neuronal function in patient-derived motor neurons, providing translational evidence for clinical development.

4. Advance a patented peptide-PMO platform towards clinical translation.Generate the preclinical evidence required to support IND-enabling development while establishing a versatile CNS delivery platform applicable to other TDP-43 proteinopathies, including FTLD and Alzheimer's disease.

Candidate´s requirements:

• PhD. Holder with a background in: neuroscience, molecular biology, pharmacology, biotechnology, biomedical sciences or related disciplines.

• With prior experience working with: rodent models, molecular biology techniques (RNA extraction, RT-qPCR, digital PCR, Western blotting and immunofluorescence), cell culture (preferably human iPSC-derived neurons), and microscopy.

  Experience with antisense oligonucleotides, neurodegenerative disease models, pharmacokinetic/pharmacodynamic studies, behavioural assessment and bioinformatics/data analysis will be considered an advantage.

• Along with the general requirements from the MSCA European Postdoctoral Fellowships.

Application process:

To extend your expression of interest, please share your CV along with a cover letter and relevant testiomonials to: pascual.torres@udl.cat & talent@irblleida.cat.

Deadline: 20-August-2026