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 companys 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, Parkinsons 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.