Understanding Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 500,000 people worldwide.1 ALS causes the degeneration of motor neurons, resulting in muscle weakness and eventually muscles waste away.2 A small number of people carry abnormal genetic variations that cause their illness, while the majority of cases are spontaneous, and their ultimate cause remains unknown. Diagnosis is complex and can take about one year from the onset of symptoms.
Although the disease can strike at any age, symptoms most commonly develop between the ages of 55 and 75.2 Initial symptoms may include:2
- Muscle twitches in the arm, leg, shoulder, or tongue
- Muscle cramps
- Tight and stiff muscles (spasticity)
- Muscle weakness affecting an arm, a leg, the neck, or diaphragm
- Slurred and nasal speech
- Difficulty chewing or swallowing
In recent years, significant strides have been made in ALS research and in the availability of new medicines to support improved symptom management. These therapies target various aspects of the disease, aiming to enhance the quality of life for patients. There are currently seven drugs approved by the U.S. Food and Drug Administration (FDA) to treat ALS and its symptoms.3
Developing a new approach to ALS treatment
ABBV-CLS-7262 activates eIF2B, a key regulator of the integrated stress response (ISR) which is a pathway activated in people with ALS. In neurons exposed to cellular stressors, inhibition of the ISR by ABBV-CLS-7262 has been shown to restore normal protein synthesis and dissolve pre-formed TDP-43 containing stress granules. This effect of ABBV-CLS-7262 is of clinical interest because TDP-43 containing stress granules are thought to lead to TDP-43 inclusions, a hallmark of ALS pathology.
Watch the video below to learn about the science behind ABBV-CLS-7262.
Our ALS clinical trials
Calico and AbbVie initiated a Phase 1b in approximately 30 people with ALS to investigate the safety and drug properties of ABBV-CLS-7262. Results from this study and the basic research behind ABBV-CLS-7262 led to selection of this molecule to participate in the HEALEY ALS Platform Trial, a Phase 2/3 trial led by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital in collaboration with the Northeast ALS Consortium (NEALS) to investigate ABBV-CLS-7262 in people diagnosed with ALS (NCT05740813). ABBV-CLS-7262 is currently under clinical investigation and is not approved for any use in any markets at this time.
The most up to date information about this investigational study can be found by visiting www.clinicaltrials.gov and entering “NCT05740813” in the “Other terms” field.
About our clinical trials
Calico and our collaborative partners are committed to designing and conducting clinical studies with the highest integrity and ethical standards and we are devoted to the safety and well-being of the people who participate. All interventional clinical trials sponsored by Calico are designed in accordance with, and authorized by, the appropriate regulatory agencies. If you have additional questions, please contact us at: email@example.com.