OP-101 for ccALD
Activated microglia and astrocytes have been observed in the brain of ccALD patients. These cells are at the leading edge of demyelination and neuronal death.
Recent technology has enabled the ability to detect activated microglia by a selective biomarker for upregulation of a receptor on these cells and detection of this biomarker by positron emission tomography (PET). In ccALD patients, selective uptake of a PET imaging agent selective for activated microglia (PK11195) has been shown to correlate with increases in gadolinium enhancement by MRI.
Orpheris intends to evaluate the effectiveness of OP-101 in returning activated microglia to normal as measured by both MRI and PET after repeat dosing in ccALD patients not eligible for bone marrow transplant. It is hypothesized that bone marrow transplant facilitates the restoration of normal microglia in ccALD patients. Thus, OP-101 may offer an alternative transplant in more advanced ccALD patients.
OP-101 is able to cross the BBB when activated microglia are present as shown in several animal models of neuroinflammation. In addition, OP-101 has been demonstrated to normalize cALD patient cells stimulated by very long chain fatty acids (VLCFA) which activates microglia in ccALD patients.
Ex Vivo Proof of Concept in ccALD Patient Samples:
If OP-101 is demonstrated to reduce activated microglia by PET imaging as described above, it may have utility in a wide range of neurological diseases. In PD, HD, Alzheimer's disease (AD) and ALS patients, activated microglia have been shown to be present (using PK11195) and increase in prevalence with worsening disease course. Through the use of a selective biomarker, Orpheris intends to select patients likely to benefit from OP-101 treatment and select OP-101 doses that will normalize activated microglia, thereby reducing neuroinflammation.