The safety, pharmacokinetics (absorption), and tolerability of the investigational eIF2B activator ABBV-CLS-7262 is being evaluated in a Phase 1b clinical study to treat patients with Vanishing White Matter (VWM) Disease.
A recent article in Biospace carried an announcement by Calico Life Sciences in collaboration with AbbVie that dosing has begun on the first participant.
The term (leukoencephalopathy/ loo″ko-en-sef″ah-lop´ah-the) describes all of the brain’s white matter diseases. VWM disease is the wearing away of the brain’s tissue in its deepest and largest region.
The tissue contains millions of nerve fibers connecting parts of the spinal cord and brain that signal the nerves to communicate. Myelin, a fatty white material, protects and insulates nerve fibers. Damage to the myelin is common in these diseases.
Targeting the Cause of VWM
The primary function of the EIF2B2 gene is to create protein. Mutations have been found in VWM patients causing partial loss of EIF2B2 thereby making it difficult for the body’s cells to create proteins. ABBV-CLS-7262 is directed at the primary cause of vanishing white matter affecting any one of five subunits of the EIF2B enzyme. Variations in this enzyme lead to activation of the ISR (integrated stress response) affecting protein stability. Chronic activation of ISR is linked to several neurological disorders.
There is a belief within the research community that cells in the white matter are especially affected by an abnormal response to stresses such as injuries due to mild head trauma or infection.
VWM is characterized by cognitive decline, seizures, and impaired movement of muscles. Symptoms most often appear in children but may affect individuals at any age.
ABBV-CLS-7262 is also being investigated in two current studies as a potential treatment for people diagnosed with amyotrophic lateral sclerosis.