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Amyloidosis Research and Treatment Center - Giovanni Palladini
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Contacts

Giovanni Palladini, PI

Email: giovanni.palladini@unipv.it

Web site: www.amiloidosi.it

Members

Giovanni Palladini, PI, Full Professor, Head and Director of the medical staff

Mario Nuvolone, Associate Professor and part of the medical staff

Paolo Milani, Researcher and member of the medical staff

Laura Obici, Medical staff

Andrea Foli, Medical staff

Roberta Mussinelli, Medical staff

Marco Basset, Medical staff

Francesca Fabris, Post-doc and member of the medical staff

Francesca Benigna, Specializing doctor

Martina Nanci, Specializing doctor

Claudia Bellofiore, Specializing doctor

Alice Nevone, Specializing biologist

Paola Rognoni, Post-doc

Maria Girelli, PhD student

Giulia Mazzini, Specializing biologist

Maria Antonietta Sesta, Specializing biologist

Serena Caminito, Biologist

Chiara Corpina, Specializing biologist

Research

Systemic amyloidoses are caused by conformational changes and aggregation of autologous proteins that deposit in tissues in the form of fibrils. This process causes functional damage of the organs involved, and eventually leads to death, if left untreated.

More than 30 types of amyloidosis are classified according to the different precursor proteins. The most common systemic form is light chain (AL) amyloidosis caused by a bone marrow plasma cell clone. Other common forms are transthyretin (ATTR) amyloidosis caused by mutations increasing the ability of TTR to form amyloid or by ageing in wild-type ATTR affecting approximately 20% of men aged 80 or more, hereditary apolipoprotein AI (ApoAI) amyloidosis prevalent in eastern Lombardy, and amyloidosis reactive to chronic inflammation (AA) caused by the acute phase protein SAA. In recent years, our understanding of the pathogenesis of systemic amyloidoses and our ability to treat these diseases has much improved.

In our group basic and clinical research are coupled, aiming at translating deeper understanding of disease mechanisms in better patients’ care, while innovative laboratory research often stems from attentive clinical observation of patients. Approximately 3500 evaluations of patients with systemic amyloidosis are performed at the Amyloidosis Research and Treatment Center every year.

The clinical center and the Biotechnology Research Laboratories are located at the Fondazione IRCCS Policlinco San Matteo (Pavia). Our group coordinates the Italian Amyloidosis Study Group, a network of more than 30 Italian research and clinical centers throughout the country (www.amiloidosi.it), and closely collaborates with all the major amyloid centers worldwide.

Our research interests are manifold:

(i) understanding the molecular mechanisms of systemic amyloidoses, through multi-OMICs approaches, development of pre-clinical models and clinical investigations;

(ii) developing molecular and imaging tools for accurate and early diagnosis and patients monitoring;

(iii) studying biochemical and imaging tools for staging and monitoring the disease in individual patients and in the design of clinical trials;

(iv) developing and testing more effective, targeted, and safe therapeutic approaches.

The main research methodologies employed include mass spectrometry, next-generation sequencing, next-generation flow cytometry, primary cell cultures, pharmacological studies, observational and interventional clinical studies.

The research activity of the group is supported by competitive public and private, national and international research grants. Active research funding includes PRIN (Ministry of University and Research), Ricerca Finalizzata (Ministry of Health), AIFA, AIRC, CARIPLO Foundation, and Global Bridges.

Bibliography

Early cardiac response is possible in stage IIIb cardiac AL amyloidosis and is associated with prolonged survival. Basset M, Milani P, Foli A, Nuvolone M, Benvenuti P, Nanci M, Fabris F, Bellofiore C, Merlini G, Palladini G. Blood. 2022 Jun 30:blood.2022016348. doi: 10.1182/blood.2022016348.

An N-glycosylation hotspot in immunoglobulin κ light chains is associated with AL amyloidosis. Nevone A, Girelli M, Mangiacavalli S, Paiva B, Milani P, Cascino P, Piscitelli M, Speranzini V, Cartia CS, Benvenuti P, Goicoechea I, Fazio F, Basset M, Foli A, Nanci M, Mazzini G, Caminito S, Sesta MA, Casarini S, Rognoni P, Lavatelli F, Petrucci MT, Olimpieri PP, Ricagno S, Arcaini L, Merlini G, Palladini G, Nuvolone M. Leukemia. 2022 May 24. doi: 10.1038/s41375-022-01599-w.

Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, Sanchorawala V, Gibbs S, Mollee P, Venner CP, Lu J, Schönland S, Gatt ME, Suzuki K, Kim K, Cibeira MT, Beksac M, Libby E, Valent J, Hungria V, Wong SW, Rosenzweig M, Bumma N, Huart A, Dimopoulos MA, Bhutani D, Waxman AJ, Goodman SA, Zonder JA, Lam S, Song K, Hansen T, Manier S, Roeloffzen W, Jamroziak K, Kwok F, Shimazaki C, Kim JS, Crusoe E, Ahmadi T, Tran N, Qin X, Vasey SY, Tromp B, Schecter JM, Weiss BM, Zhuang SH, Vermeulen J, Merlini G, Comenzo RL; ANDROMEDA Trial Investigators. N Engl J Med. 2021 Jul 1;385(1):46-58.

Indicators of profound hematologic response in AL amyloidosis: complete response remains the goal of therapy. Milani P, Basset M, Nuvolone M, Benigna F, Rodigari L, Lavatelli F, Foli A, Merlini G, Palladini G. Blood Cancer J. 2020 Sep 1;10(8):90. doi: 10.1038/s41408-020-00355-6.

Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis. Kastritis E, Leleu X, Arnulf B, Zamagni E, Cibeira MT, Kwok F, Mollee P, Hájek R, Moreau P, Jaccard A, Schönland SO, Filshie R, Nicolas-Virelizier E, Augustson B, Mateos MV, Wechalekar A, Hachulla E, Milani P, Dimopoulos MA, Fermand JP, Foli A, Gavriatopoulou M, Klersy C, Palumbo A, Sonneveld P, Johnsen HE, Merlini G, Palladini G .J Clin Oncol. 2020 Oct 1;38(28):3252-3260. doi: 10.1200/JCO.20.01285.