Spark ignited: first HD patient dosed in new Roche gene therapy trial

Spark Therapeutics, recently integrated into Roche Pharmaceuticals, has been working on an HD gene therapy. It’s delivered via a one-time brain surgery and is designed to lower levels of the huntingtin protein. A (very) small safety study has recently begun, and so far, one brave individual has received this experimental therapy, known as RG6662 (or SPK-10001). Let’s discuss how company relationships fuel clinical progress, and what’s next in the development of the drug. 

The relationship between Spark and Roche

To capture your interest with a romance, let’s talk about how these companies found themselves holding hands. Spark began as a biotech company about a decade ago, based on academic research at the University of Pennsylvania. They developed the first ever gene therapy for an inherited disease (Luxterna) to treat a type of vision loss. Roche became particularly interested in this, as well as their work on a blood disorder called hemophilia, ultimately purchasing the company in 2019. 

While fully owned by Roche, Spark continued to grow, building a big scientific campus for discovery and manufacturing, and working on more gene therapies, including one for HD. In 2024-2025 the company went through a bunch of restructuring, and in May of 2025, Roche announced a new relationship status: Spark has been fully integrated. That means Roche now has full control of how Spark is managed, how it operates, and the future of the drugs they have developed. 

Taking an HD drug from its academic research origins, starting then growing a company, and partnering with an even larger one to enable clinical development – that’s a story arc we can commit to following! 

RG6662/SPK-10001

When a big company acquires a drug in development, they usually rename or renumber it according to their own system. We’ve mentioned SPK-10001 in our coverage of major HD conferences like the 2024 annual meeting of the Huntington Study Group and the 2025 CHDI HD Therapeutics Conference. Now (gasp) it’s taken Roche’s name: RG6662.

It is an experimental gene therapy, packaged inside of a harmless virus called an AAV. When it is injected directly into the brain, it can spread to many brain areas and deliver genetic instructions (creating a microRNA) to tell the cells to stop producing the huntingtin protein. RG6662 lowers both expanded huntingtin – the kind that arises from extra CAG repeats and can harm brain cells – and wild type huntingtin – the kind that is a healthy length. The goal is to lower huntingtin for a very long period of time with a single treatment, in hopes that this could slow or stop the worsening of HD symptoms. 

Going public

Now that we’ve binged the first few seasons, let’s get up to date on the storyline. The Spark-Roche connection has birthed a new gene therapy trial of RG6662/SPK-10001. A June 12^th letter directed specifically to HD families and shared by advocacy organizations, stated that the first patient had been dosed in a small clinical trial. If it feels like this baby came out of the blue, rest assured that there have been massive efforts behind the scenes to take this new HD drug from bench to bedside. 

Notably, Spark representatives have presented updates on the pre-clinical science at the biggest recent HD conferences. Last November we touched on their efforts in primates to test the drug’s safety and confirm its ability to spread to different areas of the brain, lowering huntingtin for up to a year. In February they shared data from mouse and primate studies that looked more closely at dosing, delivery, and biomarkers like NfL. They have also talked about their work to optimize the surgical procedure, and their plans for the upcoming trial. 

The trial itself

The study will have multiple parts and it will move forward over several years. Spark and Roche announced initiation of the first part of the study (Part A), which will now pass fully into Roche’s hands. It will run in the USA and is planned to involve participants with early HD aged 25-65, with a CAG repeat length of 40 or more, who are mostly independent in their activities and care, and have a loved one who can be their study companion. In Part A, 8 participants will receive RG6662, as an injection into the caudate and putamen – the parts of the brain most vulnerable in HD.

Part A takes it slow, checking very carefully for safety. If all seems to be going well for the first recipient of RG6662 (they will be monitored for at least a few months), then Roche will proceed with the next participant. There may also be a “dose escalation” to test whether a higher amount of drug might be better. “Our team will learn from each participant’s experience, and we will adjust the study based on learnings,” Roche and Spark shared in the joint announcement.  

Part B of the study will include a placebo arm, so some of the participants will receive a “sham” brain surgery with no drug delivered. Then Part C would allow those who were assigned a placebo to receive RG662 later on, and Part D will involve long-term follow-up of all of the participants to look at safety and effectiveness over a much longer period of time. 

Looking to the future

We’ll have our eyes peeled for more news around the progress of this trial, of course – and we’re excited that another gene therapy has reached the clinic. What’s also notable here is the public display of affection partnership and engagement. Not all companies make joint community-facing announcements about the initiation of a study. Both Spark and Roche have a history of partnering with advocacy organizations early in drug development, and Roche’s learnings from the GENERATION HD1 and GENERATION HD2 trials will surely inform their strategy in HD moving forward. They have partnered with the Huntington Study Group, an organization with many years of experience running HD trials, to carry out the study. 

All in all, years of data and exploration in animals as well as many touchpoints with the HD community allowed Spark and Roche to move ahead with the design of a clinical trial in people. It’s particularly encouraging when companies use their knowledge, partnerships, and community connections not only to make scientific decisions around dosing and delivery, but also to integrate safety and support measures that meet the needs of people with HD and their companions. We’ll be sure to keep you in the loop as more sparks fly. 

TL;DR

• Spark Therapeutics, now fully integrated into Roche, has launched a small safety trial of a one-time gene therapy for HD called RG6662 (formerly SPK-10001).
• Delivered via brain surgery, the therapy uses an AAV vector to lower both mutant and normal huntingtin protein levels.
• The first participant has received the treatment, marking a major milestone after years of research.
• The multi-phase trial, starting in the U.S. with early-stage HD patients, will gradually assess safety and dosing before expanding.
• Spark and Roche’s collaboration emphasizes transparency and patient engagement, building on past HD trial experiences to guide their approach.

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