Alzheimer’s disease (AD) is the most common form of dementia. The disease worsens as it progresses. Although AD develops differently for every individual, there are many common symptoms. In the early stages, the most common symptom is difficulty in remembering recent events, known as short-term memory loss. As the disease advances, symptoms can include confusion, irritability, aggression, mood swings, trouble with language, and long-term memory loss. Gradually, bodily functions are lost, ultimately leading to death. Because AD cannot be cured and is degenerative, the affected patients must increasingly rely on others for assistance.
Current approved drugs for AD treat symptoms of the disease only and do not halt the progression or provide sustainable improvement of the disease. The positive effects of these treatments on cognitive functions and activities of daily living are at best modest and transient and may have side effects.
Scientific insight into the disease has identified a major hallmark of its biology, Abeta peptides. These peptides were identified as being the main constituent of senile plaques which were originally regarded as the toxic component that destroys brain cells, also referred to as neurodegeneration. On this basis, therapeutic concepts were developed aiming at modifying the disease by halting or slowing the progression of the neurodegeneration (disease modification). The first generation of disease modifying approaches focused on inhibiting the plaque production or reducing existing plaques by targeting Abeta in general.
Probiodrug’s Differentiated Approach
The prevailing scientific view today, however, is that it is not the plaques but soluble Abeta aggregates, which are called “Abeta oligomers”, that cause the early pathological changes in AD (Shankar and Walsh, 2009; Sheng et al., 2012; Shankar et al., 2008; Walsh and Selkoe, 2004; Walsh and Selkoe, 2007). The formation of these toxic soluble Abeta oligomers is triggered by a specific form of Abeta, namely pGlu-Abeta (Nussbaum et al., 2012).
In 2004 Probiodrug’s scientists discovered that pGlu-Abeta needs a specific enzyme to be formed, called Glutaminyl Cyclase (QC) (Schilling et al., 2004). The discovery of this key enzyme which leads to pGlu-Abeta, is the basis for Probiodrug’s development of small molecule QC- inhibitors, as a specific pGlu-Abeta targeting treatment approach.
Probiodrug is developing product candidates to specifically target toxic pGlu-Abeta via two complementary modes of action, i.e. by (i) inhibiting the production of pGlu-Abeta; and (ii) clearing existing pGlu-Abeta from the brain, which the Company believes are complementary.