What side effects are associated with this type of intervention?

Gene expression modulation treatments for Huntington's Disease, such as those targeting specific single nucleotide polymorphisms (SNPs) like WVE-003, are still under investigation. Common side effects of gene therapy approaches can include immune reactions, inflammation, and off-target effects that may lead to unintended gene modifications. More broadly, treatments for HD often involve medications to manage symptoms, which can cause side effects such as gastrointestinal issues, psychiatric symptoms, and motor disturbances. As research progresses, more specific side effect profiles for SNP-targeting therapies will become clearer.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically targeting gene expression modulation via SNP targeting for Huntington's Disease. The primary FDA-approved treatments for Huntington's Disease focus on managing symptoms rather than altering the genetic expression of the disease. These include tetrabenazine and deutetrabenazine for chorea (involuntary movements) associated with Huntington's Disease. Other treatments are aimed at managing psychiatric symptoms and improving quality of life.

What other types of research exist?

Promising alternatives to WVE-003 for Huntington's Disease treatment in 2024 include: 1) Allele-selective transcriptional repression using ZFP-TFs, which can selectively repress over 99% of HD-causing alleles while preserving normal alleles. 2) RNA interference (RNAi), which has shown improvements in motor and neuropathological abnormalities in HD mouse models. 3) Antisense oligonucleotides (ASOs) targeting single nucleotide polymorphisms for allele-selective suppression of mutant Huntingtin, which have demonstrated tolerability and efficacy in pre-clinical models. 4) Gene editing technologies like TALEN and CRISPR/Cas, which are being explored for their potential to correct genetic mutations at the DNA level.

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Antisense Oligonucleotide

WVE-003 for Huntington's Disease

Phase 1 & 2

Waitlist Available

Research Sponsored by Wave Life Sciences Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Ambulatory, male or female patients aged ≥25 to ≤60 years

Presence of the A variant of SNP3 on the same allele as the pathogenic CAG triplet expansion

Must not have

Implantable CNS device that may interfere with ability to administer study drug via lumbar puncture or undergo MRI scan

Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called WVE-003 in adults with early-stage Huntington's Disease who have a specific genetic marker. The goal is to see if the drug is safe and effective by changing how certain genes work.

Who is the study for?

This trial is for adults aged 25-60 with early-manifest Huntington's Disease, who can walk and have certain scores on the UHDRS scale. They must carry a specific genetic marker (SNP3-A variant) linked to their condition. People who've had other experimental drugs recently or have conditions that make lumbar punctures risky can't join.

What is being tested?

The study tests WVE-003, a potential treatment for Huntington's Disease. Participants are randomly assigned to receive either WVE-003 or a placebo without knowing which one they're getting. The trial will assess safety, how well the body handles the drug (PK), and its effect on disease markers (PD).

What are the potential side effects?

Since this is an early-phase trial for WVE-003, detailed side effects aren't fully known yet. Generally, participants may experience issues related to the administration of the drug via lumbar puncture and possible reactions similar to other oligonucleotides.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 25 and 60 years old and can walk.

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My genetic test shows I have the A variant of SNP3 linked to my condition.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any implants in my brain or spine that could interfere with spinal injections or MRI scans.

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I have a condition that could make a spinal tap risky or difficult.

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I have previously been treated with tominersen.

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I haven't had cancer or cancer treatment in the last 5 years, except for skin cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: WVE-003 (Dose C) or placeboExperimental Treatment1 Intervention

Group II: WVE-003 (Dose B) or placeboExperimental Treatment1 Intervention

Group III: WVE-003 (Dose A) or placeboExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

WVE-003

2021

Completed Phase 2

~50

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Huntington's Disease (HD) that focus on gene expression modulation, such as WVE-003, work by targeting specific single nucleotide polymorphisms (SNPs) to reduce the production of the mutant huntingtin protein. This approach involves the use of antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) that bind to the mutant mRNA, promoting its degradation or preventing its translation. By lowering the levels of the toxic protein, these treatments aim to slow disease progression and alleviate symptoms. This is crucial for HD patients as it addresses the root cause of the disease at the genetic level, potentially offering more effective and long-lasting benefits compared to symptomatic treatments.

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