Tazbentetol shows retinal neuroprotection potential in diabetic mouse model

An experimental drug has shown potential to protect retinal nerve cells from damage associated with diabetes, raising the possibility of a new approach to treating diabetic retinal neuropathy. 

Published by Spinogenix, the peer-reviewed research found that tazbentetol, formerly known as SPG302, protected retinal structure and function in a genetic mouse model of diabetes.

The findings could be relevant to diabetic retinopathy (DR), a leading cause of vision loss in which neurodegenerative changes can occur alongside or before detectable damage to retinal blood vessels.

Protecting retinal function

In the study, when compared with untreated diabetic mice, animals receiving tazbentetol showed better preservation of retinal ganglion cell function and survival. The treatment also restored levels of proteins involved in synaptic function, reduced markers associated with retinal stress and cell death and improved a measure of optic nerve myelination.

Tests of retinal and visual pathway function also showed improvements. Tazbentetol reversed reductions in pattern electroretinogram amplitude, a measure associated with retinal ganglion cell viability, and shortened the latency of pattern visual evoked potentials, which reflects the speed of signals travelling along the visual pathway.

Importantly, the retinal effects occurred without changes to blood glucose, insulin resistance or body weight, suggesting the treatment’s effects were not simply a consequence of improving diabetes itself.

These findings further validate tazbentetol’s potential to protect retinal neurons in diseases characterised by early synapse loss. For the millions of people affected by vision loss due to diabetic retinal disease, there remains a significant need for treatments that address the underlying drivers of disease progression. We are encouraged by this data, demonstrating that synaptic restoration can potentially play a significant role in disease management.”

Dr Stella Sarraf, Chief Executive Officer and Founder, Spinogenix

 

Targeting an earlier stage of disease

Diabetic retinopathy is usually linked to changes in the blood vessels when supplying the retina. However, neurodegeneration is also increasingly recognised as an important part of the disease.

Diabetic retinal neuropathy (DRN) can occur early in the disease process and involves damage to the inner retina, including retinal ganglion cells and their synapses. Increased cellular stress and neuronal death can follow.

There are currently no approved treatments specifically targeting the neurodegenerative processes underlying DRN, creating an opportunity for approaches that intervene before more advanced retinal damage develops. 

“Synapse loss is increasingly recognised as an early and important driver of neurodegeneration across retinal diseases, including diabetic retinal neuropathy,” said Dr Robert Weinreb, Chair and Distinguished Professor of Ophthalmology at University of California, San Diego, and member of Spinogenix’s scientific advisory board. ”These findings build on prior work in a model of glaucoma and demonstrate the ability of tazbentetol to preserve retinal ganglion cells, maintain synaptic integrity and protect retinal function in response to diverse neuronal stressors.”

What happens next?

The findings are promising but remain preclinical and will need further study before establishing whether tazbentetol can prevent or reverse retinal nerve damage in people with diabetes.

Tazbentetol is a once-daily oral treatment designed to restore synaptic function. The drug has already been investigated in Phase II clinical trials for Alzheimer’s disease, ALS and schizophrenia and is currently available through an expanded access programme for ALS.

For diabetic retinal disease, further research will need to establish whether the neuroprotective effects seen in mice translate to humans and whether synaptic restoration can alter the progression of vision loss.