ALDEA Pharmaceuticals was founded by Stanford University researchers on the discovery of small-molecule modulators of the aldehyde dehydrogenase enzyme (ALDH) family. The ALDH-based proprietary technology has been licensed exclusively. With this platform, ALDEA has the unique opportunity to pursue novel targets across multiple therapeutics areas to address significant unmet medical needs:
ALDH superfamily enzymes catalyze aldehyde oxidation which is critical for aldehyde detoxification. Aldehydes form adducts with macromolecules, damage and inactivate proteins and DNA, inducing cellular damage; several are known carcinogens.
There are 19 ALDH genes/isozymes in the human genome. They play important roles in embryogenesis and development, oxidative stress, neurotransmission, and cancer. They are present in cytosol, mitochondria, endoplasmic reticulum and nucleus, with broad tissue distribution.
Examples of ALDH Isoenzymes
ALDEA is a pioneer in developing ALDH-targeted therapeutics; the company is building a portfolio to capture innovative product opportunities.
Ethanol alcohol is first broken down primarily by Alcohol Dehydrogenase enzyme (ADH) into acetaldehyde. Acetaldehyde is toxic, and it is subsequently metabolized primarily by ALDH2 into harmless acetate.
However, a common mutation in ALDH2 exists that significantly reduces the metabolism of acetaldehyde and leads to Alcohol Metabolism Deficiency (ALMD).
ALDEA has small molecules that restore the activity of variant ALDH2, thus representing a treatment for the signs and symptoms of ALMD
Prevalence of ALMD in Asia.
Adapted from Figure 1, Li et al.,
Annals of Human Genetics 2009
Approximately 36% of East Asians carry a single gene mutation in ALDH2 resulting in impaired enzyme function, which leads to accumulation of acetaldehyde after drinking alcohol.
Commonly known as "Asian Flush", or "Asian Glow", ALMD results in elevated acute and chronic toxicity from acetaldehyde.
After even small amounts of alcohol, individuals with ALMD experience symptoms including:
- Early and intense facial flushing
- Perspiration, headache and palpitations
- Rapid heartbeat and elevated blood pressure
- Rapid intoxication, vomiting and severe hangovers
- Elevated long-term risk of cancer, especially oral and esophageal cancers due to DNA and tissue damage.
ALDEA is developing an oral drug to accelerate acetaldehyde metabolism by targeting to ALDH2 enzyme and optimizing its catalytic activity. This will minimize accumulation of acetaldehyde and reduce incidence and severity of acute toxic effects after alcohol consumption in an individual with ALMD. Other formulations may be developed to address more severe intoxication situations.
Lead optimization is ongoing for two additional programs: ALDH2 activators to treat Fanconi Anemia and ALDH1 inhibitors to target cancer stem cells.