Organs-on-chip technology reveals new drug candidates for Lou Gehrig's disease

The investigation of amyotrophic lateral sclerosis (ALS) - also known as Lou Gehrig's disease - through muscle-on-a-chip technology has revealed a new drug combination that may serve as an effective treatment of the progressive neurodegenerative disease. These findings highlight organ-on-a-chip technologies - in which live conditions of the body are mimicked in a microfluidic cell culture - as promising platforms for testing drug candidates and investigating the pathogenesis of ALS, which remains largely unknown.

The disease currently impacts around 12,000 to 15,000 people in the U.S. ALS involves the loss of motor neurons in the spinal cord and motor cortex, which leads to progressive paralysis, muscle atrophy and death. While roughly 10% of ALS patients have a familial version of the disease, which can typically be traced back to a genetic mutation, 90% of patients have "sporadic ALS," which has no known familial links or causes. As the few FDA-approved drugs currently on the market for ALS lack full effectiveness, there is an urgent need for ALS therapy investigations in the clinic, using better clinical models that can go beyond the limitations of animal models. Here, Tatsuya Osaki and colleagues created disease-on-a-chip technology-based approach. It features a microfluidic chip loaded with healthy skeletal muscle bundles and induced pluripotent stem cell-derived, light-sensitive motor neurons from a sporadic ALS patient. Light was used to activate muscle contraction and control neural activity on the chips.

Compared to chips with non-ALS-patient-derived cells, the ALS-on-a-chip exhibited fewer and weaker muscle contractions, degraded motor neurons, and increased muscle cell death. Application of two neuroprotective molecules - rapamycin and bosutinib (both in clinical trials) - helped recover muscle contraction induced by motor neuron activity and improve neuronal survival in the chip-based model of disease. Importantly, each treatment on its own has a limited ability to penetrate the blood-brain barrier, but when combined, the molecular duo could efficiently cross blood-brain-barrier-like cell layers built onto the chip.

Tatsuya Osaki, Sebastien GM Uzel, Roger D Kamm1.
Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons.
Science Advances 10 Oct 2018, Vol. 4, no. 10. doi: 10.1126/sciadv.aat5847.

Most Popular Now

Novartis rises to second place in 2018 Access to M…

Novartis ranked second in the 2018 Access to Medicine Index (ATMi), up from 3rd place in 2016, in recognition of its long-standing efforts to improve worldwide access to ...

Sanofi builds focus on rare blood disorders and ca…

Some of the most serious unmet patient needs today are in the field of hematology. Rare blood disorders and blood-related cancers continue to be a major focus of research...

MSD is looking for a digital health solution to em…

MSD Lebanon is looking for an external partner to co-create a digital solution that helps oncologists to stay updated with relevant clinical content about cancer. The sol...

FDA approves new treatment for patients with acute…

The U.S. Food and Drug Administration today approved Daurismo (glasdegib) tablets to be used in combination with low-dose cytarabine (LDAC), a type of chemotherapy, for t...

Lilly submits New Drug Application to the FDA for …

Eli Lilly and Company (NYSE: LLY) has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for lasmiditan for the acute...

Merck and Pfizer provide update on avelumab in pla…

Merck and Pfizer Inc. (NYSE: PFE) today announced that the Phase III JAVELIN Ovarian 200 trial evaluating avelumab* alone or in combination with pegylated liposomal doxor...

New study reveals probiotics do not help children …

Probiotics are a multibillion-dollar industry with marketing claims of being an effective treatment for a multitude of ailments, including diarrhea. However, findings fro...

U.S. FDA approves Larotrectinib, the first TRK inh…

The U.S. Food and Drug Administration (FDA) has approved larotrectinib, the first oral TRK inhibitor, under the brand name Vitrakvi®. The approval is for the treatment of...

FDA approves first treatment for Lambert-Eaton mya…

The U.S. Food and Drug Administration today approved Firdapse (amifampridine) tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults. LEMS is a r...

Bristol-Myers Squibb awards "Golden Tickets…

Bristol-Myers Squibb Company (NYSE: BMY) and LabCentral, an innovative, shared laboratory space designed as a launchpad for life-sciences and biotech startups, today anno...

Alcon to highlight its vision, strategy and benefi…

Alcon, the eye care division of Novartis, will today hold its first Capital Markets Day for investors and analysts in relation to the previously-announced intention of No...

FDA grants breakthrough device designation to arti…

Bayer announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Device Designation to the Artificial Intelligence Software for Chronic Thrombo...