When viewing this topic in a different language, you may notice some differences in the way the content is structured, but it still reflects the latest evidence-based guidance.

Huntington disease

View PDF
  • Overview
  • Theory
  • Diagnosis
  • Management
  • Follow up
  • Resources
Last reviewed: 29 Nov 2025
Last updated: 28 Oct 2025
28 Oct 2025

AMT-130 gene therapy slows disease progression in patients with Huntington disease

AMT-130, a gene therapy which uses RNA interference to lower levels of mHTT (mutant huntingtin) protein, has shown promising results in one phase 1/2 study. Based on information from press releases, initial topline results from the European arm of the study indicate that the therapy has the potential to slow disease progression, giving hope to patients with Huntington disease.

The study met its primary endpoint, with a statistically significant 75% slowing of disease progression with high-dose AMT-130 compared with control at 36 months, as measured using the composite Unified Huntington Disease Rating Scale. A secondary endpoint was also met, with high-dose AMT-130 showing a statistically significant 60% slowing of disease progression as measured by Total Functional Capacity. Favorable trends were also found across additional clinical measures of motor and cognitive function, mean cerebrospinal fluid neurofilament light protein (NfL) levels reduced below baseline at 36 months, and the therapy was well tolerated with a manageable safety profile.[109]

A single dose of the drug is expected to last a lifetime. The Food and Drug Administration (FDA) has previously granted AMT-130 breakthrough therapy designation and regenerative medicine advanced therapy designation, programs designed to accelerate the development and review of new drugs. It is anticipated that a biologics license application will be submitted to the FDA in 2026 requesting accelerated approval of the drug.[109][110]​ AMT-130 currently also has orphan drug designation in Europe.

See Management: emerging

Original source of update

Summary

Definição

História e exame físico

Principais fatores diagnósticos

  • positive family history of Huntington disease
  • known expansion of the CAG repeat length at the N-terminal end of the huntingtin gene
  • impaired work or school performance
  • personality change
  • irritability and impulsivity
  • chorea
  • twitching or restlessness
  • loss of coordination
  • deficit in fine motor coordination
  • slowed rapid (saccadic) eye movements
  • motor impersistence
  • impaired tandem walking
Detalhes completos

Outros fatores diagnósticos

  • concentration impairment/task anxiety or apathy
  • cognitive decline relative to partner/siblings
  • changes in personal habits/hygiene
  • disinhibition or unusually anxious behavior
  • depression, obsessions, and compulsions
  • sleep disturbance
Detalhes completos

Fatores de risco

  • expansion of the CAG repeat length at the N-terminal end of the huntingtin gene
  • other genetic factors
  • family history
Detalhes completos

Investigações diagnósticas

Primeiras investigações a serem solicitadas

  • no initial tests
Detalhes completos

Investigações a serem consideradas

  • genetic test for cytosine-adenine-guanine (CAG) repeat expansion
  • MRI or CT scan
Detalhes completos

Algoritmo de tratamento

CONTÍNUA

all patients

Colaboradores

Autores

Mitsuko Nakajima, MD

Clinical Research Fellow

Huntington's Disease Centre

Queen Square

Institute of Neurology

Department of Neurodegenerative Disease

Russell Square House

London

UK

Declarações

MN is funded by the clinical fellowship scheme from the Huntington's Disease Society of America, a nonprofit organization that funds research into Huntington disease. There is no contractual agreement to disseminate product information.

Agradecimentos

Dr Mitsuko Nakajima would like to gratefully acknowledge Dr Peter McColgan, Dr Sarah Tabrizi, Dr David Craufurd, Dr Marianne Novak, and Dr Francis Walker, previous contributors to this topic.

Declarações

FW declared that he had no competing interests. MN is an author of a reference cited in this topic. DC has received fees for advisory board membership from Hoffmann-La Roche Ltd. SJT has received grant funding for her research from CHDI Foundation, the BBSRC, Dementia and Neurodegenerative Disease Network UK, European Huntington’s Disease Network, Huntington’s Disease Association of the UK, the Medical Research Council UK, Takeda Pharmaceuticals, the UCL/UCLH Biomedical Research Center, and the Wellcome Trust. SJT has been on advisory boards or had consultancies with F. Hoffmann-La Roche Ltd, Ixico Technologies, Shire Human Genetic Therapies, Takeda Pharmaceuticals International, and TEVA Pharmaceuticals; all honoraria for these consultancies and advisory boards were paid to UCL. Through the offices of UCL Consultants Ltd, a wholly owned subsidiary of UCL, SJT has undertaken consultancy services for F. Hoffmann-La Roche Ltd and GSK. ST is also an author of references cited in this topic PM declared that he had no competing interests.

Revisores

Adrian Priesol, MD, FRCPC

Instructor

Massachusetts Eye and Ear Infirmary

Harvard Medical School

Boston

MA

Declarações

AP declares that he has no competing interests.

Tiago Mestre, MD, MSc

Resident Neurology

Neurological Clinical Research Unit

Institute of Molecular Medicine

Lisbon

Portugal

Declarações

TM declares that he has no competing interests.

Créditos aos pareceristas

Os tópicos do BMJ Best Practice são constantemente atualizados, seguindo os desenvolvimentos das evidências e das diretrizes. Os pareceristas aqui listados revisaram o conteúdo pelo menos uma vez durante a história do tópico.

Declarações

As afiliações e declarações dos pareceristas referem--se ao momento da revisão.

Referências

Nossas equipes internas de editoria e de evidências trabalham em conjunto com colaboradores internacionais especializados e pares revisores para garantir que forneçamos acesso às informações o mais clinicamente relevantes possível.

Principais artigos

Bean L, Bayrak-Toydemir P; American College of Medical Genetics and Genomics. Standards and guidelines for clinical genetics laboratories, 2014 edition: technical standards and guidelines for Huntington disease. Genet Med. 2014 Dec;16(12):e2.Texto completo  Resumo

Anderson KE, van Duijn E, Craufurd D, et al. Clinical management of neuropsychiatric symptoms of Huntington disease: expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders. J Huntingtons Dis. 2018;7(3):355-66.Texto completo  Resumo

Bachoud-Lévi AC, Ferreira J, Massart R, et al. International guidelines for the treatment of Huntington's disease. Front Neurol. 2019;10:710.Texto completo  Resumo

Quinn L, Kegelmeyer D, Kloos A, et al. Clinical recommendations to guide physical therapy practice for Huntington disease. Neurology. 2020 Feb 4;94(5):217-28.Texto completo  Resumo

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.

  • Diagnósticos diferenciais

    • Tardive dyskinesia
    • Dentatorubro-pallidoluysian atrophy (DRPLA)
    • Neuroacanthocytosis
    Mais Diagnósticos diferenciais

  • Diretrizes

    • Clinical guidance in neuropalliative care: an AAN position statement
    • Clinical recommendations to guide physical therapy practice for Huntington disease
    Mais Diretrizes

  • Folhetos informativos para os pacientes

    Depression in adults

    Huntington’s disease

    Mais Folhetos informativos para os pacientes
  • padlock-lockedConectar-se ou assinar para acessar todo o BMJ Best Practice

O uso deste conteúdo está sujeito ao nosso aviso legal