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Dr. Urano’s August update

Fumihiko “Fumi” Urano, MD

Dr. Fumihiko “Fumi” Urano, MD

Dear Friends,

I hope you had a wonderful summer season. I would like to update you about our progress.

Our clinical trial of dantrolene sodium in patients with Wolfram syndrome is ongoing. We have been monitoring the safety, tolerability, and efficacy of the drug. Some patients have been taking dantrolene sodium for more than 6 months, and we have started getting the safety, tolerability, and efficacy data. We plan to publish the data once we collect the information from 20 patients. I have started preparing for the next phase of this trial. As I mentioned in my previous blog, we are considering the following possibilities.

  1. A longer duration, More participants, Multi-center
  2. Include the placebo arm. I understand that nobody wants to take the dummy drug for a long period of time. So I have been getting advice from medical officers conducting clinical trials for rare diseases.

In addition to dantrolene sodium, my team has been looking into two new drugs for Wolfram. Unlike dantrolene sodium, these drugs are new. So we need to carefully collect more data from mouse models of Wolfram and healthy human subjects.

  1. The first drug is an endoplasmic reticulum (ER) calcium stabilizers which we discovered together with NIH/NCATS. This drug is for delaying/halting the progression of the disease. Pre-clinical studies in mouse models of Wolfram are ongoing.
  2. The second drug is a chemical chaperone which reduces ER stress. We have started collaboration with a biotech company on this new drug.

I am aware that we need to find a way to improve visual acuity. I am trying to secure funds for testing our new regenerative gene therapies for optic nerve degeneration using a novel neurotrophic factor in combination with gene transfer technology. I have applied for multiple grants and am quite hopeful about the outcome.

Thank you for your continued support. I cannot thank you enough.

Take care,

Fumi Urano, MD

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Eye Problems in Wolfram Syndrome

Professor Patrick Yu-Wai-ManProfessor Patrick Yu-Wai-Man

Affiliations

  1. John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge
  2. MRC Mitochondrial Biology Unit, University of Cambridge
  3. Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals
  4. Moorfields Eye Hospital and UCL Institute of Ophthalmology, London

I am an eye doctor (ophthalmologist) with a particular interest in genetic eye diseases. I look after patients with Wolfram syndrome in my specialist clinic and I also lead a research group that is investigating ways of slowing or preventing loss of vision in patients affected with this relatively rare genetic disorder.

How is visual information sent from the eye to the brain?

visual info to brain

The eye is a very sensitive camera that converts an image from the outside world into an electrical signal. At the back of the eye is the optic nerve, which is similar to a high-speed “broadband cable” that allows this electrical signal to be sent quickly to the vision centres at the back of the brain to be decoded. The figure above illustrates how visual information gets from the eye to the brain via the connecting optic nerve.

What is optic atrophy?

The majority of patients with Wolfram syndrome will develop optic atrophy. Optic atrophy means that the optic nerve has been damaged and it looks pale in colour when the eye doctor looks at the back of the eye with the appropriate equipment. Because the optic nerve is damaged, less visual information is sent from the eye to the brain, and this also happens more slowly with transmission errors. As a result, patients with Wolfram syndrome start to struggle with their central vision and they find it increasingly difficult to read small print and make out people’s faces (as in the example shown below). Visual difficulties usually start in childhood and they tend to get progressively worse with time.

optic atrophy

What other eye problems can you get in Wolfram syndrome?

  1. Diabetes is very common in Wolfram syndrome, but fortunately diabetic eye complications tend to be rare. Nevertheless, patients with Wolfram syndrome need to take particular care that their blood sugar levels are well controlled to avoid further diabetic eye complications in addition to optic atrophy.
  2. A small group of patients with Wolfram syndrome can develop cataracts at a young age. If the eye doctor spots that a cataract is present and vision is getting worse because of it, the option of cataract surgery can be discussed.

What treatments can we offer at the moment?

  1. Unfortunately, there is currently no proven treatment to stop the damage to the optic nerve and loss of vision. There is a lot of research being carried out at the moment to look for drugs that can protect the optic nerve. Gene therapy is also being considered, but this strategy is still an early stage of development and so far, studies have only been carried out in mice.
  2. As there are no effective treatments yet for the optic atrophy in Wolfram syndrome, visual rehabilitation is very important and children, especially, must be provided with the right level of support at school.

How frequently should an eye check-up be carried out?

All patients with Wolfram syndrome should ideally have an annual check-up. Drops will usually be put in the eyes to dilate the pupils and make it easier to have a careful look at the back of the eye for any changes since the patient’s last visit.

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