Research on the TDP-43 protein opens new therapeutic avenues for ALS

Sunday, June 21, 2026, Madrid, Spain – Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, the nerve cells responsible for controlling voluntary muscle movement. As the disease progresses, it causes a gradual loss of mobility, speech, swallowing, and respiratory function, while cognitive abilities remain preserved in most cases.

On the occasion of World ALS Day, observed on June 21, the Spanish Bioindustry Association (AseBio) is highlighting a disease for which significant unmet medical needs still remain. In Spain, between 4,000 and 4,500 people are currently living with ALS, and approximately 900 new cases are diagnosed each year, equivalent to nearly three diagnoses per day. The disease is also associated with a high mortality rate: approximately three people die from ALS every day in Spain. Average survival is typically between two and five years following diagnosis, although there is considerable variability among patients.

Despite advances in the understanding of the disease, therapeutic options remain limited, and there is still no cure capable of stopping or reversing its progression. Diagnosis continues to be challenging and may be delayed by more than a year after the onset of the first symptoms, hindering early access to specialized care and potential clinical trials.

In this context, biotechnology is driving new approaches aimed at addressing the molecular causes of the disease. One of the most promising areas of research focuses on the TDP-43 protein, whose dysfunction is present in the majority of ALS patients and plays a key role in neuronal degeneration. Molefy Pharma, an AseBio member company, is developing AP-2, an innovative molecule for ALS designed to restore TDP-43 function. Following the granting of orphan drug designation by the European Medicines Agency (EMA) and authorization from the Spanish Agency for Medicines and Medical Devices (AEMPS) to initiate clinical trials in humans, we spoke with its CEO, Alfonso de Egaña Barrenechea, about the latest advances and challenges in ALS research.

According to Alfonso de Egaña Barrenechea, ALS research is currently experiencing a particularly promising moment, driven by the growing commitment of the scientific community, patient associations, and the biotechnology sector. However, he emphasizes that significant unmet medical needs remain. He also points out that there are still no pharmacological treatments capable of significantly slowing or halting disease progression, making it essential to continue advancing the development of new therapeutic strategies that can improve both patient outcomes and quality of life.

Alongside advances in research, the CEO of Molefy Pharma highlights the importance of strengthening comprehensive care for people living with ALS. In this regard, he considers the establishment of dedicated ALS units in all major referral hospitals to be a priority. These units should be staffed by multidisciplinary teams capable of addressing, in a coordinated manner, the diverse needs of patients and their families.

He also stresses the need for sustained investment in research to support long-term projects, particularly those focused on the discovery and development of new treatments.

TDP-43: A Key Therapeutic Target in ALS

One of the areas currently generating the greatest scientific interest is the study of the TDP-43 protein. According to De Egaña, this protein plays an essential role in the functioning of cells in the nervous system and shows alterations in more than 97% of ALS cases.

“ALS can today be defined as a TDP-43 proteinopathy, that is, a disease of the TDP-43 protein,” he states. The formation of toxic aggregates and the loss of function of this protein disrupt key cellular processes and contribute to the neuronal death characteristic of the disease.

Based on this evidence, Molefy Pharma is developing AP-2, a molecule designed to restore TDP-43 function. To date, studies have shown a reduction in pathological aggregates and a recovery of normal protein function in preclinical models. “If the effects observed in cellular and animal models were replicated in humans, AP-2 could represent a treatment capable of modifying the course of the disease,” explains the company’s CEO.

The recent authorization to initiate clinical trials in humans represents, in this context, a decisive step toward evaluating the safety and efficacy of this therapeutic approach in patients with sporadic ALS.

Biotechnology, Precision Medicine, and Biomarkers in ALS

Looking ahead to the coming years, Molefy Pharma expects the approach to ALS to evolve toward increasingly complex and personalized therapeutic strategies. These include the combination of different drugs with complementary mechanisms of action, the development of multi-target treatments, and advances in precision medicine.

The company also focuses on the development of biomarkers and omics technologies, tools that will enable earlier diagnosis, improve patient selection, and optimize clinical trial design.

Despite the uncertainties that still surround the disease, Molefy Pharma looks to the future with optimism and is confident that advances in basic research, drug discovery, and biomarker development will contribute to a better understanding of ALS and to the development of more effective treatments that improve both the quality and length of patients’ lives.