Daniel Claassen, MD, MS

“Just using these 2 SNPs—SNP1 and SNP2&mdash;if there’s a potential therapy for modifying mutant huntingtin in an allele-specific manner, almost two-thirds of patients would qualify based on our findings.”

Data recently collected by a group of investigators including Daniel O. Claassen, MD, MS, suggest that clinical trials could feasibly use investigative agents targeting single nucleotide polymorphisms (SNPs) that are allele-selective to address a significant portion of the population with Huntington disease (HD).

The associate professor of neurology in the Department of Cognitive and Behavioral Neurology and Movement Disorders at Vanderbilt University Medical Center explained to 

 that he and colleagues used next-generation sequencing to assess the feasibility. Their data showed heterozygosity of SNP1 and/or SNP2 in 72% (n = 146) of patients, with the 2 polymorphisms linked only with the mutant 

) allele in 61% (95% high-density interval: 55—67) of individuals.

In this interview, Claassen offered his perspective on the data and provided an overview of the takeaways for the clinical community. He suggested that this confirmation is really one of the first steps at truly developing personalized medicine in the treatment of patients with HD, and spoke to the next steps that need to be taken with the agents in the pipeline that could address this need: Wave Life Science’s SNP1 and SNP2 candidates WVE-120101 and WVE-120102.&shy;

Claassen DO, Corey-Bloom J, Dorsey ER, et al. Genotyping single nucleotide polymorphisms for allele-selective therapy in Huntington disease. 

. 2020;6(3):e430. doi: 10.1212/NXG.0000000000000430

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The associate professor of neurology at Vanderbilt University Medical Center offered his perspective on the feasibility of genotyping, phasing, and targeting of SNPs in Huntington disease.

Daniel Claassen, MD, MS: Takeaways from SNP Research in Huntington Disease

“[These SNPs] are actually far, far away from the CAG repeat. They’re thousands of base pairs away, so the methodological advances that were taken to do this [sequencing] was quite impressive.”

Daniel O. Claassen, MD, MS, associate professor of neurology, Cognitive and Behavioral Neurology and Movement Disorders, Vanderbilt University Medical Center, and colleagues recently conducted a study utilizing a next-generation sequencing method in Huntington disease which showed heterozygosity of SNP1 and/or SNP2 in 72% (n = 146) of patients in their assessment. The 2 polymorphisms were associated only with the mutant 

All told, the data suggest that allele-selective therapies may potentially address a significant portion of the population with Huntington disease. With 2 such therapies in the pipeline from Wave Life Sciences that target SNP1 and SNP2—WVE-120101 and WVE-120102&mdash;this highlights an important opportunity to answer what Claassen describes as a “fundamental question” about Huntington: Is it safe and effective to knock-down wild type Huntington protein expression?

To find out more about the sequencing method used and what the findings of this study can tell the clinical community treating Huntington, 

The associate professor of neurology at Vanderbilt University Medical Center spoke to the findings of a recent study in Huntington disease that assessed the feasibility of selectively knocking down mutant protein expression.

Daniel Claassen, MD, MS: Selective Knock-Downs in Huntington Disease

“SNPs are kind of randomly dispersed polymorphisms in the genetic code, and there have been data that show that there is a certain SNP that is more commonly present in some people than others. The question was could they design a technology that would take advantage of that SNP being on the same allele as the mutant Huntington expansion?”

Recent study findings from a group of investigators suggest that it is feasible to undergo clinical trials using single nucleotide polymorphisms (SNPs)-targeting candidates—such as Wave Life Sciences SNP1 and SNP2 candidates WVE-120101 and WVE-120102&mdash;and that allele-selective therapies may potentially address a significant portion of the population with Huntington disease (HD).

The study, conducted by Daniel O. Claassen, MD, MS, associate professor of neurology, Cognitive and Behavioral Neurology and Movement Disorders, Vanderbilt University Medical Center, and colleagues, identified heterozygosity of SNP1 and/or SNP2 in 72% (n = 146) of those in their assessment. The 2 polymorphisms were associated only with the m

 allele in 61% (95% high-density interval: 55—67) of individuals.

To find out more about what brought this study together and prompted Claassen and colleagues to undertake the work, 

 sat down with him. He offered his perspective on the investigation and provided a brief history of the understanding of SNPs in HD.

The associate professor of neurology at Vanderbilt University Medical Center offered his perspective on his and colleagues’ study of single nucleotide polymorphisms in Huntington disease.

Daniel Claassen, MD, MS

Articles

Daniel Claassen, MD, MS: Takeaways from SNP Research in Huntington Disease

Daniel Claassen, MD, MS: Selective Knock-Downs in Huntington Disease

Daniel Claassen, MD, MS: Allele-Selective Therapy for Huntington Disease