Clinical Trials

Trials in the United States

Amylyx Pharmaceuticals Announces First Participant Dosed in Phase 2 Study of AMX0035 for the Treatment of Wolfram Syndrome

https://www.amylyx.com/news/amylyx-pharmaceuticals-announces-first-participant-dosed-in-phase-2-study-of-amx0035-for-the-treatment-of-wolfram-syndrome

AMYLYX Phase 1/2 Clinical Trial

Please click on the link for the Phase ll Study of Safety and Efficacy of AMX0035 in Adult Patients with Wolfram syndrome. For further information and how to apply click the link below.
https://clinicaltrials.gov/ct2/show/NCT05676034?term=amx0035&draw=2&rank=1Amylyx

Our mission is to one day end the suffering caused by neurodegenerative diseases. Currently, there are no approved treatments to stop or slow the progression of Wolfram syndrome (WS), and we are committed to exploring the potential of AMX0035 (sodium phenylbutyrate and taurursodiol) in WS based on preclinical findings. We plan to initiate a Phase 1/2 clinical trial, proof of concept study, assessing the potential of AMX0035 for the treatment of WS.AMX0035 is hypothesized to target pathways central to WS and has shown effects in a variety of models of WS.The FDA granted orphan drug designation to AMX0035 for the treatment of WS in November 2020. 

Neil H. White, MD

Telephone: (314) 286-1157

Bess A. Marshall, MD

Telephone: (314) 454-6051

Fumihiko Urano, MD, Ph.D.

Tamara Hershey, PhD

Trials Abroad

Dr. Barrett

Scientific Advisor

Telephone: +44 (0)121 414 7966
Fax: +44 (0)121 414 4486

Email: t.g.barrett@bham.ac.uk
Twitter: @euro_wabb

Address
Room WX 2.55 , Second Floor
IBR West
The Medical School
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Tim Barrett lay person summary

Development of a novel repurposed drug treatment for the neurodegeneration and diabetes in Wolfram syndrome. 

One in 17 of the UK population suffers from a rare disease. There are over 6,000 rare diseases, many of which are life limiting, and almost all have no cure. Wolfram syndrome is a rare disease (1:700,000; about 100 people in the UK) that causes diabetes and blindness in children and young people. These children may grow up to develop other problems such as deafness, loss of bladder control, loss of balance, and sometimes depression. The disease is life limiting because of damage to brain cells and brain shrinkage. The only way to look after affected people is to treat the complications: there is no cure, and no treatment to prevent or slow down the progression of the disease.

The goal of our research team is to develop a treatment that will prevent or delay the disease getting worse. We believe that such a treatment will offer longer, better quality of life for affected people.

Our research team at Birmingham University developed a cell model of Wolfram syndrome, and used it to screen for medicines that can treat the disease. We found one, sodium valproate, that reduces cell death in our cell model of Wolfram. Sodium valproate is a really promising candidate as it has been used for decades to treat epilepsy in children. It is licenced for use in epilepsy. We also know that it improves the diabetes in a mouse model of Wolfram syndrome. However, like all medicines, it does have side effects. It should not be used in people with liver disorders, or people with mitochondrial disorders caused by mutations in the POLG gene. It must not be used in pregnancy. It can sometimes cause mood changes, anaemia, nausea, disturbed periods, weight increase, and tremor. Therefore, we need to test its safety and effectiveness for Wolfram patients, in a clinical trial. We are only allowed to prescribe it to patients, once we have shown that it is safe; and that it works to slow down the disease process.

On 14th December, the UK Medical Research Council awarded £2million ($2.5Million) funding to the Birmingham UK team to lead a clinical trial of sodium valproate in children and adults with Wolfram syndrome. This will be the first randomised controlled trial in Wolfram syndrome. The aim of the clinical trial is to show that sodium valproate is safe, and effective, in people with Wolfram syndrome. We will invite 70 children and adults with Wolfram syndrome to take part. These will be from people attending 5 centres: Birmingham adults (Dr Ben Wright) and children (Dr Renuka Dias); Almeria (Dr Gema Esteban Bueno); Paris (Pr Christophe Orssaud); Montpellier (Pr Christian Hamel); Lodz (Pr Wojciech Mlynarski).

The study period will run for 36 months. We will check that valproate is safe, and effective as a treatment for Wolfram. We will do this by closely monitoring for any side effects; and by careful measurements of vision, brain volume, and other features, as the trial continues. We already know how quickly the disease gets worse with no treatment. This trial will give us a clear answer as to whether sodium valproate slows down the disease process, or not.

If the trial shows us that valproate is safe in Wolfram syndrome and slows down the progress of the disease, then this will give us the evidence to prescribe valproate to Wolfram patients in the clinic. Most importantly, we hope this trial will improve the quality and length of life in patients with Wolfram syndrome.

Clinical Trial Update by Dr. Barrett- January 2024

Timothy Barrett 

Tim Barrett update for Winter TreatWolfram newsletter

Dear friends and colleagues,

I hope everyone is keeping OK and are keeping warm enough in this cold weather. Our research teams have kept busy and I would like to use this letter to keep you updated on our progress.

The TREATWOLFRAM trial is now in its final year. It has been a long journey to get here, navigating medicine manufacture problems, BREXIT, Covid, and supply issues. Thank you to all the participants who have supported the trial with their involvement. Our trials unit team, Amy Lamb, Lewis James Victoria Homer and Darren Barton, are working hard to make sure all the information that participants have kindly supplied, will be ready to be analysed when the trial ends in October 2024. There has been an update from the UK Medicines Regulator (MHRA) to remind patients and the public about the safety precautions we all need to follow for people taking sodium valproate. Anyone female under 55 years who may be taking sodium valproate, needs to have a safety check with their doctor each year. It is important that sodium valproate should not be taken by women who may be pregnant, as there is a risk of significant harm to the baby. There is helpful information on this UK Government website:https://www.gov.uk/guidance/valproate-use-by-women-and-girls .

Our laboratory team, led by Dr Sovan Sarkar, with Dr Malgosia Zatyka, and their colleagues, have been finding new biological pathways in cells that are important in developing Wolfram syndrome. Some of these pathways relate to the ways that cells clear unwanted by-products. Sovan’s team have studied these pathways to look for new treatments to correct the defects. They have some candidate medicines, and have applied to research funders to test if thesemedicines work in cell models. Sovan’s team presented at a major conference hosted in Birmingham at the end of the Summer, and one of his team members won the prize for best presentation.

Finally, our team has been approached by researchers in Europe and North America, to support their work on Wolfram syndrome. The team in North America are looking at changes in DNA that silence or activate genes and how these affect symptoms in Wolfram syndrome. The team in Europe are hoping to set up a new clinical trial of a treatment for Wolfram, and we are sharing our expertise, data and samples to help push this research forward

All our study team owes a big thank you to Wolfram syndrome UK for their generous support, and for bringing the Wolfram community of families, researchers and health care professionals together.

Sincerely

Dr. Tim Barrett

Past Trials

Fumihiko Urano, MD, PhD

Scientific Advisor

Samuel E. Schechter Professor of Medicine

Office Location:
8808A Wohl Hospital

Mailing Address:
660 S. Euclid Ave
Campus Box 8127
St. Louis, MO 63110

Office Phone: (314) 362-8683
Fax: (314) 362-8265

Cris Brown, Wolfram Syndrome Registry Manager:
(314) 362-8684

Email
urano@dom.wustl.edu

Researchers at Washington University School of Medicine in St. Louis are launching a new clinical trial to assess the safety of a drug treatment for patients with the rare disease Wolfram syndrome.

Wolfram syndrome affects about one in every 500,000 people worldwide. Many of those patients die prematurely from the disease. Patients with Wolfram syndrome typically develop diabetes at a very young age and require insulin injections several times each day. The disorder also causes hearing loss, vision problems and difficulty with balance.

Although doctors treat patients’ symptoms, there have not been any therapies that slow the syndrome’s progress.

However, researchers at Washington University School of Medicine soon will test a drug treatment in 24 patients who have the genetic disorder.

The scientists previously reported in the Proceedings of the National Academy of Sciences that the drug, dantrolene — a muscle relaxant approved to treat patients with cerebral palsy, multiple sclerosis and muscle spasticity — prevents the destruction of insulin-secreting beta cells in animal models of Wolfram syndrome and in brain cells differentiated from skin samples taken from patients with the illness.

“Nobody has ever tested dantrolene in patients with Wolfram syndrome, so our first and most important objective is to make sure it’s safe,” said principal investigator Fumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine. “I am very hopeful, however. The major question that I get from every patient I see is, ‘Is there any treatment?’ And until now, I’ve had to say no. With any luck, perhaps this study can help change that.”

In the mouse studies, and in experiments with brain cells made from a patient’s own stem cells, Urano previously found that dantrolene prevented death of brain cells and insulin-secreting beta cells.

Urano’s team plans to study 12 adult and 12 pediatric patients over nine months. All of the participants will undergo extensive testing before they begin taking the medication and after having taken the drug for six months. The researchers will closely monitor patients’ vision and brain function, as well as the function of their remaining insulin-secreting beta cells.

To be eligible for the study, all patients must be able to travel to the Washington University Medical Campus for testing and medication.

The study is funded by the Snow Foundation and the Ellie White Foundation. Both are advocacy groups that support Wolfram syndrome research. Urano also has applied for federal funding to support the clinical trial and wants to expand it to other medical centers.

He doubts that dantrolene can reverse the illness. “But hopefully, we can at least delay the progression of the disease,” he said.

For more information, call study coordinator Ashley Simpson at 314-286-1550, or e-mail ashley.simpson@wustl.edu.

Article by Jim Dryden