Multiple Sclerosis

With more than 2.3 million people globally fighting the disease, multiple sclerosis (MS) is one of the most common diseases of the brain and spinal cord.  MS is an autoimmune disease of the central nervous system where the immune system attacks myelin causing demyelination.  Myelin forms a protective covering around nerves, allowing them to rapidly transmit signals to efficiently facilitate vision and coordinate body movement. 

Today’s approved MS therapies are aimed at reducing the immune system attack on myelin.  On the flip-side of the problem, Novoron is pursuing a novel therapeutic approach to remyelinate.  Remyelination is intended to protect the neurons from further damage and maintain function. 

Novoron observed that RAP could block Rho activation by inhibiting LRP1 and restore neuronal outgrowth in vitro.  LRP1 is an established receptor for myelin debris and contributes to inhibition of remyelination via activation of Rho.  Rho and Rho-kinase are well considered targets for multiple sclerosis, but are difficult to effectively inhibit therapeutically.  Novoron is testing RAP, which can attenuate Rho activation both in vitro and in vivo and is actively transported across the blood brain barrier in vivo.


Spinal Cord Injury

Spinal cord injury causes lost connectivity due to damaged or severed axons.  Currently, there are no clinically viable drugs to address this loss and restore connectivity.  For the millions living with or those who are newly affected by spinal cord injury, axonal regeneration is the main hope to reverse paralysis.

In spinal cord injury, neurons are inhibited in their natural regenerative capacity by molecular signals at the site of injury.  Novoron is developing novel biologic therapeutics which overcome this suppression of neuronal regrowth, thereby restoring the natural regeneration program inherent to these damaged neurons, without the need of invasive implants or foreign cells. 

In recent years, most attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A, OMgp, and myelin-associated glycoprotein (MAG).  Binding of MAIs to neuronal cell-surface receptors leads to activation of RhoA, growth cone collapse, and neurite outgrowth inhibition.

LRP1 is as a high-affinity, endocytic receptor for MAG. In contrast with previously identified MAG receptors, binding of MAG to LRP1 occurs independently of terminal sialic acids. In primary neurons, functional inactivation of LRP1 with receptor-associated protein, depletion by RNA interference (RNAi) knock-down, or LRP1 gene deletion is sufficient to significantly reverse MAG and myelin-mediated inhibition of neurite outgrowth.  Novoron has developed a novel way to inhibit LRP1 and is currently performing preclinical research to test this approach.


Glaucoma

One of the predominant characteristics contributing to vision loss in glaucoma is the increase of intraocular pressure (IOP).  Increases in IOP are associated with gradual loss of neurons in the retina, which is responsible for transmitting vision signals to the brain.  Agents capable of reducing IOP are the primary therapeutic avenue towards improving long-term outcomes in this disease.  

Novoron is developing a biologic therapeutic designed to reduce IOP with the additional potential benefit of protecting the neurons that become “at risk” from this disease.  This work is being developed in collaboration with Dr. Jeffrey Goldberg, professor and chair of Ophthalmology at Stanford University.