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Apoptosis Regulators Provide Targets for Cancer Therapy

Apoptosis Regulators Provide Targets for Cancer Therapy

LA JOLLA, California--Idun Pharmaceuticals, a biopharmaceutical company founded in 1994, is focusing its resources on the design and development of small molecule drugs targeting the biochemical pathways that control apoptosis, or programmed cell death.

President and CEO Steven J. Mento, PhD, said the company is developing agents that control the function of key proteins involved in the apoptotic pathway: the caspase protease family of apoptosis effectors and the Bcl-2 family of apoptosis modulators (see illustration). Identification of the key genes and gene products that regulate the apoptosis pathway has provided greater understanding of the role of apoptosis in both normal and disease states.

The company’s cancer program targets members of the Bcl-2 family. Recent studies have shown that, in many cancer cells, Bcl-2 proteins are upregulated, resulting in increased activity that protects the cancer cells from apoptosis and allows them to grow and accumulate unchecked. Agents that block Bcl-2 function would, in theory, restore normal apoptosis and lead to tumor regression.

Dr. Mento said that Idun, in collaboration with Novartis, is also exploring methods to treat neurodegenerative diseases, such as stroke, Parkinson’s disease, and amylotrophic lateral sclerosis, in which excessive apoptosis contributes to nerve cell loss. In these disorders, aberrant apoptosis can stem from either inappropriate caspase protease activity or loss of protection by an imbalance of Bcl-2 family proteins.

Limiting Brain Damage in Stroke

Idun and Novartis researchers have already shown that inhibiting the action of caspase protease family proteins can promote neuronal survival and limit brain damage in animal models of stroke. Inhibitors of specific caspases have been identified and are being optimized for in vivo activity, with stroke as an initial indication.

The company is also exploring the use of caspase protease inhibitors to prevent liver damage associated with organ transplantation or alcoholic hepatitis as well as to prevent the apoptosis that contributes to the ischemic injury occurring during a heart attack.

 
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