What are the current treatment recommendations for Huntington's disease (HD)?

From the Guidelines

Currently, the most effective treatment approach for Huntington's disease (HD) focuses on managing symptoms and improving quality of life, as there is no cure available, and this is supported by the American College of Medical Genetics and Genomics standards and guidelines for clinical genetics laboratories, 2014 edition 1. The treatment plan should be individualized based on symptom presentation, as HD affects each person differently.

• For movement disorders, tetrabenazine (12.5-25 mg, 1-3 times daily) or deutetrabenazine (6-48 mg daily in divided doses) are FDA-approved to reduce chorea.
• Antipsychotics like risperidone (0.5-2 mg daily) or olanzapine (2.5-10 mg daily) may help with both chorea and psychiatric symptoms.
• For depression, SSRIs such as sertraline (50-200 mg daily) or escitalopram (10-20 mg daily) are commonly used.
• Mood stabilizers like valproate (250-500 mg twice daily) can help with irritability and aggression.
• Physical therapy, occupational therapy, and speech therapy are essential components of treatment to maintain function and independence.
• Nutritional support is important as the disease progresses, sometimes requiring feeding tubes in advanced stages. A multidisciplinary approach involving neurologists, psychiatrists, psychologists, genetic counselors, physical therapists, and social workers provides the most comprehensive care, and treatment plans must be regularly monitored and adjusted to balance symptom control with side effects, as stated in the technical standards and guidelines for Huntington disease 1.

From the FDA Drug Label

The efficacy of tetrabenazine tablets as a treatment for the chorea of Huntington’s disease was established primarily in a randomized, double-blind, placebo-controlled multi-center trial (Study 1) conducted in ambulatory patients with a diagnosis of HD. The primary efficacy endpoint was the Total Chorea Score, an item of the Unified Huntington’s Disease Rating Scale (UHDRS). As shown in Figure 1, Total Chorea Scores for patients in the drug group declined by an estimated 5.0 units during maintenance therapy (average of Week 9 and Week 12 scores versus baseline), compared to an estimated 1.5 units in the placebo group.

The current recommendation for treatment of Huntington's disease is tetrabenazine, which has been shown to be effective in reducing chorea scores in patients with HD.

• The treatment effect of 3.5 units was statistically significant.
• About 50% of tetrabenazine-treated patients achieved a 6-point or greater improvement in chorea score.
• A Physician-rated Clinical Global Impression (CGI) favored tetrabenazine statistically. 2

From the Research

Current Treatment Options for Huntington's Disease

• Tetrabenazine is a dopamine-depleting agent that has been approved by the US Food and Drug Administration (FDA) for the treatment of chorea associated with Huntington's disease 3, 4, 5.
• Deutetrabenazine, a structurally similar compound to tetrabenazine, has also been approved by the FDA for the treatment of chorea associated with Huntington's disease and tardive dyskinesia 6.
• Other treatment options for Huntington's disease include antipsychotic medication, antidepressants, mood stabilizing medication, and non-drug therapies, which can help manage symptoms such as chorea, behavioral and psychiatric abnormalities, and cognitive decline 7.

Efficacy and Safety of Current Treatments

• Tetrabenazine has been shown to be effective in reducing chorea severity in patients with Huntington's disease, with a significant benefit on ratings of clinical global improvement 4.
• Deutetrabenazine has also demonstrated consistent efficacy in reducing chorea severity and improving quality of life in patients with Huntington's disease, with a safety profile similar to that of placebo 6.
• However, tetrabenazine has been associated with potentially serious adverse effects, such as depression, anxiety, and suicidal ideation, and should be dosed individually based on ongoing assessment of possible adverse side effects 4, 5.

Future Therapeutic Options

• Several new therapeutic options are currently undergoing clinical trials, including antisense oligonucleotide (ASO) therapies, RNA interference (RNAi) therapies, and stem cell therapies, which target the disease at its origin by lowering the levels of mutant huntingtin protein (mHTT) 7.
• Other potential therapies in pre-clinical development include Zinc-Finger Protein (ZFP) therapies, transcription activator-like effector nuclease (TALEN) therapies, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) therapies 7.