Wave SELECT HD: when one is better than two

– Written by the Moving Forward team on February 7th, 2023

Wave is a strong contender in the Huntingtin lowering drug race. Their approach is a bit different from other companies, as their ASO is only trying to silence the expanded copy of the HD gene, while leaving the other copy of the gene alone. In other words, the company wants to selectively target the mutated Huntingtin protein and preserve the unaffected Huntingtin protein, based on the hypothesis that keeping the healthy protein might be beneficial for the person affected by HD.

We do not remove both eyes, we put an eye patch on the abnormal eye and keep the normal eye seeing, explains Ralf Reilmann, the HD expert neurologist founder of the George-Huntington Institute and one of the German principal investigators of SELECT HD.

The downside of this selective approach is that it is far more complex than other Huntingtin-lowering experimental therapies and requires the patient to have the right SNP3 changes for the drug to work. So not everyone will be able to benefit from this specific therapy in the short term. The SELECT HD trial is a small phase 1b/2a clinical trial that wants to check if the drug WVE-003 is safe and determine what should be the effective dosing regimen to reduce the levels of the mutated Huntingtin protein.

SELECT HD aims to enroll around 36 persons with early manifest Huntington’s disease, aged between 25 and 60 years old. The study is running in Australia, Canada, Denmark, France, Germany, Italy, Poland, Spain and the UK and is still recruiting.

Last September, Wave informed the community that a preliminary monitoring of the efficiency of the drug showed that the WVE-003 treatment with 30 or 60 mg led to a 20-30% reduction of the levels of the mutant Huntingtin protein, while the levels of the regular Huntingtin stayed about the same.

Thus, the preliminary data suggests that the WVE-003 is working as expected – it is able to selectively reduce the toxic Huntingtin protein and maintain the healthy Huntingtin protein and its beneficial effects in the central nervous system.  Although these first findings create a lot of excitement and positive expectations in the HD community, we must not forget that this selective approach contains a challenge because only about 40% of HD gene carriers have the variant A on SNP3 and thus can be eligible for this potential treatment.

Nevertheless, we believe that the development of a selective approach to HD mutant Huntingtin lowering is a very significant breakthrough in the field of HD research, which we think will provide unvaluable data for developing effective treatments to stop Huntington’s disease in the future.

Moreover, we need to acknowledge that personalized medicine is an emerging and increasingly strong practice that is moving forward based on the human genome project, which allow us to select the best approach to a specific disease based on the genetic profile of the people affected by that disease. Being able to choose the right drug, at the right dose, for the right person based on their genetics is a true revolution in the field of medicine. Having this cutting-edge approach also in the field of Huntington’s disease is also a true revolution and really encouraging for us.

More details about SELECT HD can be found here: