Offering Hope for Victims of Degenerative Diseases

Our NAALADase inhibitor program is aimed at developing a medicinally and commercially sound way to block excessive glutamate release, which is believed to play a key role in many central and peripheral neurodegenerative conditions.



The Need:
Diabetic neuropathy is a debilitating and progressive disorder involving increased pain sensitivity, tingling, weakness and numbness in a patient's extremities. It is believed to affect close to one million Americans, yet there are no approved drugs to treat this disabling condition.

The News:
Through leading-edge neuroprotectant research, Guilford is developing novel inhibitors of an enzyme called NAALADase that may offer hope for individuals with diabetic neuropathy and other disabling chronic or acute neurodegenerative disorders. NAALADase inhibitors are believed to work by providing protection against damage to human cells by regulating excessive harmful levels of a common neurotransmitter, glutamate. In preclinical studies, NAALADase inhibitors also promote the production of myelin – a protective sheath, which surrounds peripheral nerves.

The Background:
NAALADase or N-Acetylated-Alpha-Linked-Acid-Dipeptidase is a membrane-bound enzyme found principally in the central and peripheral nervous system. NAALADase is believed to play a role in modulating the release of glutamate in the nervous system. Glutamate is one of the brain's most common chemical messengers. Under normal conditions, glutamate is released into a microscopic space -- called the synapse -- that exists between neurons in the brain. There, it stimulates post-synaptic glutamate receptors, an action that is critical to such functions as learning, memory and motor control. However, during conditions of acute injury or chronic disease, there is a large increase in glutamate release that incites a cascade of biochemical events, ultimately leading to cell injury and death.

The Development Strategy:
With the goal of offering new treatment alternatives, Guilford is evaluating the use of its NAALADase inhibitors as potential protective therapies for chronic neurodegenerative disorders. Guilford has created several unique classes of NAALADase inhibitors as a way to diversify its research and maximize potential therapeutic applications in peripheral neuropathy, chronic pain, schizophrenia, Lou Gehrig's Disease (ALS), epilepsy, head and spinal cord trauma, stroke, Alzheimer's and Parkinson's disease.

The Status:
In tissue culture and in animal models of diabetic neuropathy, Guilford's NAALADase inhibitors appear to normalize pain sensitivity, increase nerve conduction velocity and promote remyelination of nerves (myelin is the insulation surrounding nerves that helps to facilitate nerve conduction). Guilford is currently pursuing a worldwide development partner for the NAALADase technology.


This page was last updated on Tuesday, March 11, 2003

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