Therapeutic Advances in Huntington's Disease

被引:49
|
作者
Shannon, Kathleen M. [1 ]
Fraint, Avram [1 ]
机构
[1] Rush Med Coll, Dept Neurol Sci, Chicago, IL 60612 USA
关键词
Huntington disease; Huntington's disease; review; treatment; experimental therapeutics; TRANSGENIC MOUSE MODEL; DEEP BRAIN-STIMULATION; GOOD CLINICAL-PRACTICE; MUTANT HUNTINGTIN; PHARMACOLOGICAL-TREATMENT; PSYCHIATRIC-SYMPTOMS; AXONAL-TRANSPORT; OXIDATIVE STRESS; REDUCES TOXICITY; UP-REGULATION;
D O I
10.1002/mds.26331
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Huntington's disease is a rare hereditary degenerative disease with a wide variety of symptoms that encompass movement, cognition, and behavior. The genetic mutation that causes the disease has been known for more than 20 y, and animal models have illuminated a host of intracellular derangements that occur downstream of protein translation. A number of clinical trials targeting these metabolic consequences have failed to produce a single effective therapy, although clinical trials continue. New strategies targeting the protein at the level of transcription, translation, and posttranslational modification and aggregation engender new hope that a successful strategy will emerge, but there is much work ahead. Some of the clinical manifestations of the illness, particularly chorea, affective symptoms, and irritability, are amenable to palliative strategies, but physicians have a poor evidence base on which to select the best agents. Clinical trials since 2013 have dashed hopes that coenzyme Q10 or creatine might have disease-modifying properties but suggested other agents were safe or hinted at efficacy (cysteamine, selisistat, hydroxyquinoline) and could proceed into later-stage disease modification trials. The hunt for effective symptom relief suggested that pridopidine might be shown effective given the right outcome measure. This review summarizes recent progress in HD and highlights promising new strategies for slowing disease progression and relieving suffering in HD. (c) 2015 International Parkinson and Movement Disorder Society
引用
收藏
页码:1539 / 1546
页数:8
相关论文
共 50 条
  • [1] Therapeutic advances in Huntington's disease
    Estevez-Fraga, Carlos
    Aviles Olmos, Iciar
    Mananes Barral, Veronica
    Lopez-Sendon Moreno, Jose Luis
    [J]. EXPERT OPINION ON ORPHAN DRUGS, 2016, 4 (08): : 809 - 821
  • [2] Therapeutic Advances for Huntington's Disease
    Kumar, Ashok
    Kumar, Vijay
    Singh, Kritanjali
    Kumar, Sukesh
    Kim, You-Sam
    Lee, Yun-Mi
    Kim, Jong-Joo
    [J]. BRAIN SCIENCES, 2020, 10 (01)
  • [3] Therapeutic advances in neural regeneration for Huntington's disease
    Francesco D’Egidio
    Vanessa Castelli
    Giorgia Lombardozzi
    Fabrizio Ammannito
    Annamaria Cimini
    Michele d’Angelo
    [J]. Neural Regeneration Research, 2024, (09) : 1991 - 1997
  • [4] Therapeutic advances in neural regeneration for Huntington's disease
    D'Egidio, Francesco
    Castelli, Vanessa
    Lombardozzi, Giorgia
    Ammannito, Fabrizio
    Cimini, Annamaria
    d'Angelo, Michele
    [J]. NEURAL REGENERATION RESEARCH, 2024, 19 (09) : 1991 - 1997
  • [5] Huntington's disease: From molecular basis to therapeutic advances
    Krobitsch, Sylvia
    Kazantsev, Aleksey G.
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2011, 43 (01): : 20 - 24
  • [6] Current Therapeutic Advances in Patients and Experimental Models of Huntington's Disease
    Brett, Ana C.
    Rosenstock, Tatiana R.
    Rego, A. Cristina
    [J]. CURRENT DRUG TARGETS, 2014, 15 (03) : 313 - 334
  • [7] Update on Huntington's disease: Advances in care and emerging therapeutic options
    Zielonka, Daniel
    Mielcarek, Michal
    Landwehrmeyer, G. Bernhard
    [J]. PARKINSONISM & RELATED DISORDERS, 2015, 21 (03) : 169 - 178
  • [8] Recent advances in the therapeutic development for Huntington disease
    Mestre, Tiago A.
    [J]. PARKINSONISM & RELATED DISORDERS, 2019, 59 : 125 - 130
  • [9] Therapeutic advances in Huntington's disease with relevance to other repeat expansion disorders
    Tabrizi, S. J.
    [J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2020, 28 (SUPPL 1) : 28 - 28
  • [10] THERAPEUTIC TARGETS FOR HUNTINGTON'S DISEASE
    Sorbera, L. A.
    Dulsat, C.
    Rosa, E.
    [J]. DRUGS OF THE FUTURE, 2012, 37 (06) : 437 - 443