Intermediate HTT CAG repeats worsen disease severity in amyotrophic lateral sclerosis

Maurizio Grassano^#^{1

2}, Antonio Canosa^#³, Sandra D'Alfonso⁴, Lucia Corrado⁴, Giorgia Brodini³, Emanuele Koumantakis⁵, Paolo Cugnasco³, Umberto Manera⁶, Rosario Vasta³, Francesca Palumbo³, Letizia Mazzini^{7

8}, Salvatore Gallone⁹, Cristina Moglia³, Ramita Dewan², Ruth Chia², Jinhui Ding², Clifton Dalgard^{10

11}, Raphael J Gibbs², Sonja Scholz^{12

13}, Andrea Calvo³, Bryan Traynor^#^{2

14}, Adriano Chio^#³

Affiliations

¹ Department of Neurosciences Rita Levi Montalcini, University of Turin, Torino, Piemonte, Italy maurizio.grassano@unito.it.
² National Institute on Aging Laboratory of Neurogenetics, Bethesda, Maryland, USA.
³ Department of Neurosciences Rita Levi Montalcini, University of Turin, Torino, Piemonte, Italy.
⁴ Department of Health Sciences Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont Amedeo Avogadro School of Medicine, Novara, Piemonte, Italy.
⁵ Department of Public Health and Pediatrics, University of Turin, Torino, Italy.
⁶ 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy.
⁷ University Hospital Maggiore della Carità, Novara, Piemonte, Italy.
⁸ University of Eastern Piedmont Amedeo Avogadro School of Medicine, Novara, Piemonte, Italy.
⁹ Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Piemonte, Italy.
¹⁰ Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
¹¹ The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
¹² National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
¹³ Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁴ Johns Hopkins University, Baltimore, Maryland, USA.

^# Contributed equally.

PMID: 39242198
PMCID: PMC11672072
DOI: 10.1136/jnnp-2024-333998

Intermediate HTT CAG repeats worsen disease severity in amyotrophic lateral sclerosis

Maurizio Grassano et al. J Neurol Neurosurg Psychiatry. 2024.

. 2024 Dec 16;96(1):100-102.

doi: 10.1136/jnnp-2024-333998.

Authors

Affiliations

¹ Department of Neurosciences Rita Levi Montalcini, University of Turin, Torino, Piemonte, Italy maurizio.grassano@unito.it.
² National Institute on Aging Laboratory of Neurogenetics, Bethesda, Maryland, USA.
³ Department of Neurosciences Rita Levi Montalcini, University of Turin, Torino, Piemonte, Italy.
⁴ Department of Health Sciences Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont Amedeo Avogadro School of Medicine, Novara, Piemonte, Italy.
⁵ Department of Public Health and Pediatrics, University of Turin, Torino, Italy.
⁶ 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy.
⁷ University Hospital Maggiore della Carità, Novara, Piemonte, Italy.
⁸ University of Eastern Piedmont Amedeo Avogadro School of Medicine, Novara, Piemonte, Italy.
⁹ Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Piemonte, Italy.
¹⁰ Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
¹¹ The American Genome Center, Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
¹² National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
¹³ Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁴ Johns Hopkins University, Baltimore, Maryland, USA.

^# Contributed equally.

PMID: 39242198
PMCID: PMC11672072
DOI: 10.1136/jnnp-2024-333998

No abstract available

Keywords: ALS; GENETICS; HUNTINGTON'S; MOTOR NEURON DISEASE; NEUROGENETICS.

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Conflict of interest statement

Competing interests: AChio serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Denali Pharma, AC Immune, Biogen, Lilly, and Cytokinetics and has received a research grant from Biogen. BT holds the US, Canadian and European patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion in C9orf72. BT and SS received research support from Cerevel Therapeutics. ACalvo has received a research grant from Cytokinetics. MG has received grants from the American Academy of Neurology, the American Brain Foundation and the ALS Association.

Figures

Figure 1. Survival from disease onset according to *HTT* CAG intermediate number of repeats in the Piemonte and Valle d’Aosta Register for ALS (PARALS) (A) and Answer amyotrophic lateral sclerosis (ALS) (B) cohort. (A) PARALS cohort (n = 1181). The blue line represents the survival of 79 patients with ALS carrying 27–35 CAG repeats (ie, intermediate length), and the red line represents the survival of 1102 patients with ALS carrying 26 or fewer CAG repeats (ie, normal length). (B) Answer ALS cohort (n = 476). The green line represents the survival of 30 patients with ALS carrying 27–35 CAG repeats (ie, intermediate length), and the orange line represents the survival of 346 patients with ALS carrying 26 or fewer CAG repeats (ie, normal length).

See this image and copyright information in PMC

References

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Intermediate HTT CAG repeats worsen disease severity in amyotrophic lateral sclerosis

Affiliations

Intermediate HTT CAG repeats worsen disease severity in amyotrophic lateral sclerosis

Authors

Affiliations

Conflict of interest statement

Figures

References

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