Discovering new treatments for everyone with MND matters and clinical trials play a vital role in making that happen. The success of Tofersen, an effective treatment for 2% of people with MND, has shown that MND can be treated. Even more importantly, the science behind it could help open the door to treatments for more people with MND. In recent years, we’ve seen promising developments and that momentum is set to continue into 2026 with several trials beginning and others expected to release results. Every day of research and every new discovery brings us closer to effective treatments for majority of people with MND. In this blog, we’ll highlight some of the clinical trials to watch this year.
Ulefnersen
Ulefnersen is a new gene therapy which is designed to treat people with MND who have a change in the FUS gene. In people who have a change in the FUS gene, the FUS protein becomes faulty and forms toxic clumps in the motor neurons, causing damage and cell death. Ulefnersen targets the changed FUS gene and silences it so that the body makes less of the faulty FUS protein.
A Phase 3 trial of Ulefnersen, called FUSION, is investigating if the gene therapy can slow the progression of MND. The trial is testing the therapy in 89 people with FUS MND across 16 countries, including the USA and UK. Those on the trial will either be given the drug or a placebo for 60 weeks. There is also an open label extension where everyone on the trial has the chance to receive the drug for 84 weeks after the initial trial period. Results from this trial are expected to be released later this year.
EXPERTS-ALS
EXPERTS-ALS is a platform designed to quickly test multiple promising MND drugs at the same time. It measures levels of neurofilament light chain (NfL), a marker of neuron damage, to see whether a drug can significantly reduce them. If a treatment lowers NfL across participants, it suggests early benefit and should be prioritised for larger clinical trials.
Since it began in 2024, EXPERTS-ALS has been testing three drugs called Metformin, Nifedipine and Ropinirole. This year, we are expecting results from the first analysis of the data collected during the trial. Data is collected throughout the trial, whilst people are still taking the drugs, to see whether the testing should continue or whether the drug should be removed from the trial.
A new drug is also set to be added to EXPERTS-ALS by the end of 2026. Raya Therapeutic’s RT1999, also known as Smilagenin, has previously been tested for Parkinson’s disease and is known to be safe. Previous studies in models of MND suggest that the drug could help control the production of proteins which are protective to motor neurones in MND. Testing this drug in EXPERTS-ALS will help to determine if these promising signs seen in the lab are also seen in people with MND.
VTx-002
VTx-002 is a gene therapy that is designed to treat the majority of people with MND. In around 97% of people with MND, a protein called TDP-43 becomes faulty and forms abnormal clumps, which are toxic and cause damage to motor neurons. VTx-002 delivers the instructions for the body to make an antibody which sticks to the toxic clumps of TDP-43 and kick starts the body’s immune system to remove them. Previous laboratory research has shown that VTx-002 may prevent death of motor neurons and slow disease progression in models of MND.
A Phase 1/2 trial called PIONEER-ALS is investigating the safety of VTX-002 in 12 people with MND. This is the first time that the gene therapy will be tested in humans and people on the trial will be given a single injection of one dose of the gene therapy into the base of their brain. They will be monitored for up to 5 years after the treatment to look at ongoing effects of the drug. The trial began in the USA in February this year and there are plans to open the trial in more countries in the coming months.
PrimeC
PrimeC is made from a combination of two existing prescription medicines, an antibiotic called Ciprofloxacin and a non-steroidal anti-inflammatory drug called Celecoxib. It is thought to reduce inflammation in the brain and the build-up of iron in neurons, both of which have been suggested to contribute to the damage of motor neurons. The previous phase 2 trial found PrimeC was safe and showed promising signs of slowing disease progression over the trial and open label extension.
A phase 3 trial, called PARAGON, is planned which will test PrimeC in around 300 people with MND to see if the drug might be an effective treatment for MND. Those on the trial will either be given the drug or a placebo for 48 weeks. There will also be an open label extension where everyone on the trial has the chance to receive the drug after the trial ends. The Phase 3 trial is set to begin this year in the US, Europe and Israel.
QRL-201
QRL-201 is a new gene therapy which is designed to treat the 97% of people with MND who have faulty TDP-43. When TDP-43 becomes faulty, it no longer works as it should and this causes problems with another protein called Stathmin-2. In most people living with MND, less Stathmin-2 is made by the body and this is thought to contribute to the damage to motor neurons. QRL-201 aims to increase the amount of Stathmin-2 being made.
A Phase 1 trial called ANQUR is investigating the safety of QRL-201 in 64 people with MND. This is the first time that the gene therapy is being tested in humans and people on the trial are being given either QRL-201 or a placebo for 12 weeks. They will be monitored for up to 36 weeks after the first treatment to look at ongoing effects of the drug. The trial has released some interim results which showed that QRL-201 is safe and slowed disease progression for some people with MND who had a slower rate of disease progression before the trial began.
The full results from this trial are expected to be released later this year, but following these promising interim results, there are plans to extend the trial and collect more data. The company behind the therapy are looking to begin an open label extension, meaning that everyone who was part of the trial will receive QRL-201. There are also plans to prepare for a phase 3 trial of QRL-201.
TRCN-1023
TRCN-1023 is another gene therapy designed to treat the majority of people with MND, those who have faulty TDP-43 protein. Faulty TDP-43 is linked to lower levels of another protein, called UNC13A. UNC13A plays an important role in regulating communication between neurons and muscles, but in MND the lower levels of this protein mean that it doesn’t work as effectively as it should. TRCN-1023 is designed to restore levels and function of UNC13A to normal and improve the communication between neurons and muscles.
Laboratory tests showed that TRCN-1023 works as designed, reaches the brain and spinal cord, and is safe and well tolerated in models. The results of this laboratory testing support the need for further development and testing of TRCN-1023. There are plans to test the gene therapy in people with MND in a phase 1/2 international trial called FUNCtionALS. This trial is expected to begin towards the end of this year.
You can keep up to date with other clinical trials happening in the UK and Internationally on our website.
