New insights into ALS: why damaged DNA is not repaired

A study conducted at the “Luigi Luca Cavalli-Sforza” Institute of Molecular Genetics of the National Research Council in Pavia (CNR-IGM) has produced key results in defining the molecular mechanisms underlying the accumulation of DNA damage in cells affected by Amyotrophic Lateral Sclerosis (ALS)—a devastating neurodegenerative disease that still lacks effective treatment options and is increasingly prevalent worldwide.

The research, funded by the AriSLA Foundation, involved contributions from researchers at the Institute of Translational Pharmacology (CNR-IFT), the Institute of Molecular Biology and Pathology (CNR-IBPM), Sapienza University of Rome, the University of Rome Tor Vergata, the Mondino Institute in Pavia, and IFOM in Milan.

The results, published in the scientific journal Cell Death & Differentiation, reveal that aggregates of the proteins FUS and TDP-43—which accumulate in ALS patients—prevent cells from detecting and repairing DNA damage. This leads to a rapid buildup of DNA lesions, resulting in genomic instability and cellular distress. While in healthy individuals cells are able to repair the multiple DNA injuries that occur daily through a process known as the “DNA Damage Response,” in ALS patients this cellular response does not function properly, thus contributing to neurodegeneration.

Sofia Francia, researcher at CNR-IGM and coordinator of the study, explains: “In a previous study funded by AriSLA, we had already shown that the aggregation of FUS and TDP-43 proteins blocks the ability of cells to signal and repair DNA damage. As a result, damaged DNA accumulates rapidly, compromising genomic function and harming the cell. Today, having identified the main actors involved in this dysfunction has enabled us to test, at the cellular level, a therapy using a drug already approved for its antibacterial activity, and more recently found to also have anticancer properties. The results are extremely promising, as they represent a first step that will allow us to continue the research in more advanced models and, hopefully, lead to potential new therapies.”

The study suggests repurposing an already-approved molecule for ALS treatment, offering the potential for a faster impact on patients.

“We are pleased with these results, which stem from multiple AriSLA-supported studies and confirm the importance of maintaining support for high-quality research evaluated through our rigorous peer-review process,” adds Anna Ambrosini, AriSLA Scientific Director.

ALS is one of the greatest challenges in the field of neurodegenerative diseases: diagnoses are growing exponentially in developed countries for still-unknown reasons, and the absence of effective treatments places a significant burden on national healthcare systems. By 2040, the number of people diagnosed with ALS in Europe is expected to rise by 20%—from the current 28,000 cases to approximately 35,000—partly due to the lack of effective treatments, which makes ALS an increasingly pressing issue for public health.


Contacts

Scientific contact:
Sofia Francia
CNR-IGM
sofia.francia@igm.cnr.it
+39 0382 546325

Press Office:
Francesca Gorini – francesca.gorini@cnr.it
Emanuele Guerrini – emanuele.guerrini@cnr.it
ufficiostampa@cnr.it
+39 06 4993 3383

JOINT IGM-UNIPV-IFOM Imaging Workshop

The imaging workshop jointly organized by IGM, UNIPV, and IFOM will be held on June 12 in the Falaschi Lecture Hall.

The following talks are scheduled:

  • Dario Parazzoli – IFOM (MI): Two-Photon Imaging in Cancer Research: A Window into the Tumor Microenvironment

  • Amanda Oldani – CGS, UniPV: Total Internal Reflection Fluorescence Microscopy, a Closer Look into the Great Unknown

  • Spartaco Santi – IGM (BO): From Idea to Illumination: Gustafsson’s SIM Revolution Under the Lens

  • Simone Sabbioneda – IGM (PV): Fluorescence under Pressure: Flow and Imaging Cytometry

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13th Arturo Falaschi Lecture

13th “Arturo Falaschi Lecture”
June 10, 2025
at 10:30

Aula “A. Falaschi” IGM CNR

Prof. John Diffley

Associate Research Director
Francis Crick Institute
London, UK

Understanding the Evolution

of DNA Replication

Initiation through Biochemistry

IGM Seminar – Dr. Davide Pradella

The seminar “Engineering focal oncogene amplifications: insights into the contributions of extrachromosomal DNA (ecDNA) to tumorigenesis” by Dr. Davide Pradella will take place on May 28th, 2025.

The event will be held at 2:30 PM in the Falaschi Conference Room – IGM-CNR.

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Course of Human Health and Disease

From May 5 to May 16, 2025, the course “Pioneering Strategies in Disease Modeling and Therapeutic Discovery” will be held at the Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, as part of the PhD Program in Genetics, Molecular, and Cellular Biology.

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Advanced Course from March 31 to April 11

The advanced course “Mechanisms and Pathways Controlling Nuclear and Genome Integrity” will be held at the Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza” as part of the PhD Program in Genetics, Molecular, and Cellular Biology, from March 31 to April 11, 2025.

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Giovanni Maga has left us

Professor Giovanni Maga, Director of the Department of Biomedical Sciences at the CNR and former Director of the Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, passed away in the late afternoon of Saturday, March 22, 2025. He was 59 years old.

Giovanni Maga’s life was deeply connected with that of our institute, where he began working during his university studies, including his master’s degree and specialization. After completing a postdoctoral fellowship at the University of Zurich, Maga continued his career at the Pavia institute, first as a postdoctoral fellow, then as a researcher, senior researcher, research director, and head of the DNA Enzymology & Virology Section.

In 2019, he was appointed Director of the Institute of Molecular Genetics, a role he held until 2023, when he assumed the leadership of the Department of Biomedical Sciences at the CNR.

Throughout his career, he authored over 200 articles in international journals, wrote books, and held several patents.

Dr. G. Maga had been working since his graduation on the enzymology of DNA replication. His research focused on the characterization of different enzymatic systems responsible for nucleotide metabolism and the duplication of genetic information in human cells and viruses. His interest was devoted both to the elucidation of basic molecular processes and to the exploitation of novel enzymatic targets for antiviral and anticancer chemotherapy.

He was particularly interested in elucidating the biochemical pathways involved in coupling the DNA replication and repair machinery in human cancer cells, with particular emphasis on the role(s) of specialized DNA polymerases; understanding the host-virus molecular interactions in order to develop broad-spectrum antiviral drugs.

All of us at the Institute of Molecular Genetics are deeply saddened by the loss of Giovanni—a scientist, colleague, and friend.

We extend our deepest condolences to his family and loved ones.

Asilomar 1975-2025: A seminar with Prof. Francesco Cassata

The seminar Asilomar 1975-2025: EMBO, EMBL and the Politics of Scientific Expertise, initially scheduled for February 27, will take place on Friday, March 14.

The seminar will be held by Prof. Francesco Cassata (University of Genoa and Centro Linceo “B. Segre” – Rome).

The event is scheduled for 11:30 AM in the “Arturo Falaschi” conference room at the Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza.”

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Prof. Marco Foiani at DBB

On Wednesday, February 5, at 11:00 AM, Professor Marco Foiani, Director of the IGM-CNR, will hold a seminar in the “Jucci” Conference Room of the Department of Biology and Biotechnology Lazzaro Spallanzani (Via Adolfo Ferrata, 9, 27100 Pavia PV).

The seminar will focus on “Mechanisms Controlling Nuclear and Genome Integrity.”

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IGM Retreat 2025

Three days of discussions and planning to shape the institute’s activities

The staff of the “Luigi Luca Cavalli-Sforza” Institute of Molecular Genetics participated in the annual retreat, which took place at the “La Bellotta” center in Pontenure (PC) from January 20 to 22, 2025.

The institute’s director, Prof. Marco Foiani, outlined the future challenges, focusing on the results achieved and the goals to be pursued in the coming year. He particularly emphasized the IGM mission.

During some talks and round tables, the services and technologies available at Pavia and Bologna were presented. The recently established PhD-PostDoc association was also introduced.

The positive atmosphere fostered good relations and the exchange of ideas among the various components of the IGM structure.