**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Nelson Leung1,2, Tereza Kmochová3, Ellen D McPhail4, Surendra Dasari5, Lenka Nosková3, Aleš Hnízda3, Kateřina Hodaňová3, Martina Živná3,8, Samih H Nasr4, Jakub Sikora3,8, Stanley T Crooke7, Anthony Bleyer3,8, Francis K Buadi2, Stanislav Kmoch3,8
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
2Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
3Research Unit for Rare Diseases, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
4Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
5Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
6Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic
7nLorem, Carlsbad, California, USA
8Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Institute of Pathology, First Faculty of Medicine, Charles University, Prague, Czech Republic

**Main Body of the Abstract**
BACKGROUND: Amyloid A (AA) amyloidosis is typically secondary to chronic inflammation from chronic infections or autoimmune diseases. Genetic causes have been described with hereditary periodic fever syndromes and a mutation in the SAA1 promoter but etiology in 25% of cases remain unidentified. Here, we describe the first familial AA amyloidosis secondary to a mutant SAA1 gene treated with antisense oligonucleotide (ASO).
PATIENTS: Patient was diagnosed with AA amyloidosis at age 37 by kidney biopsy. His sister was diagnosed at 31 following evaluation for proteinuria. His mother died of infectious complications following a kidney transplant for end stage renal disease (ESRD) secondary to amyloidosis. Maternal grandfather died of ESRD. Genetic testing for periodic fever syndromes was negative for both siblings and CRP was normal for the patient.
METHODS: A variant chr11: 18290751 A>T (hg19) encoding for a missense mutation in SAA1 (NM_199161.5):c.101A>T(p.D34V) was identified in both siblings. The D34V substitution was not detectable by the standard proteomics because it was hidden by the trypsin splice site. Endoprotease AspN was used to detect the D34V in the amyloid proteome. An ASO-Ga1NAc was created against the SAA1 RNA. A N of 1 trial was initiated to treat the patient. Dosing started at 40 mg and will be titrated upward to a maximum of 120 mg monthly in order to achieve a 60% suppression of SAA1 level.
DISCUSSION: We report the first familial AA amyloidosis secondary to a SAA1 mutation. A N of 1 trial has been initiated with an ASO against SAA1.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
**Nelson Leung1,2, Tereza Kmochová3, Ellen D McPhail4, Surendra Dasari5, Lenka Nosková3, Aleš Hnízda3, Kateřina Hodaňová3, Martina Živná3,8, Samih H Nasr4, Jakub Sikora3,8, Stanley T Crooke7, Anthony Bleyer3,8, Francis K Buadi2, Stanislav Kmoch3,8**
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
2Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
3Research Unit for Rare Diseases, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
4Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
5Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
6Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic
7nLorem, Carlsbad, California, USA
8Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Institute of Pathology, First Faculty of Medicine, Charles University, Prague, Czech Republic

**Main Body of the Abstract**
**BACKGROUND**: Amyloid A (AA) amyloidosis is typically secondary to chronic inflammation from chronic infections or autoimmune diseases. Genetic causes have been described with hereditary periodic fever syndromes and a mutation in the SAA1 promoter but etiology in 25% of cases remain unidentified. Here, we describe the first familial AA amyloidosis secondary to a mutant SAA1 gene treated with antisense oligonucleotide (ASO).
**PATIENTS**: Patient was diagnosed with AA amyloidosis at age 37 by kidney biopsy. His sister was diagnosed at 31 following evaluation for proteinuria. His mother died of infectious complications following a kidney transplant for end stage renal disease (ESRD) secondary to amyloidosis. Maternal grandfather died of ESRD. Genetic testing for periodic fever syndromes was negative for both siblings and CRP was normal for the patient.
**METHODS**: A variant chr11: 18290751 A>T (hg19) encoding for a missense mutation in SAA1 (NM_199161.5):c.101A>T(p.D34V) was identified in both siblings. The D34V substitution was not detectable by the standard proteomics because it was hidden by the trypsin splice site. Endoprotease AspN was used to detect the D34V in the amyloid proteome. An ASO-Ga1NAc was created against the SAA1 RNA. A N of 1 trial was initiated to treat the patient. Dosing started at 40 mg and will be titrated upward to a maximum of 120 mg monthly in order to achieve a 60% suppression of SAA1 level.
**DISCUSSION**: We report the first familial AA amyloidosis secondary to a SAA1 mutation. A N of 1 trial has been initiated with an ASO against SAA1.



Antisense oligonucleotide therapy for familial AA amyloidosis, A N of 1 trial OC12 (#193)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.