Approved Diagnostic Molecule in Preclinical Studies to Evaluate Potential in ALS

Researchers at the University of Queensland in Australia have begun preclinical studies of macimorelin, Aeterna Zentaris’ approved oral diagnostic, as a potential treatment for amyotrophic lateral sclerosis (ALS).

The preclinical development program, led by Frederik Steyn, PhD, is part of a recent agreement between university researchers and Aeterna that provides the latter exclusive right to create a licensing agreement for macimorelin’s commercial use for the treatment of ALS.

“The start of the preclinical phase represents a significant milestone in the development of a potential new treatment option for ALS to help patients with this terrible, incurable disease and to improve their quality of life,” Klaus Paulini, PhD, Aeterna’s CEO, said in a press release. “We look forward to supporting Dr. Steyn’s research team in addressing this significant unmet medical need.”

Aeterna’s lead product, macimorelin is an orally available small molecule approved for the diagnosis of adult growth hormone deficiency in both the U.S. and Europe. It is sold as Macrilen in the U.S. by Novo Nordisk.

Growth hormone deficiency is a rare condition in which the body does not produce enough growth hormone (GH), leading to a wide range of symptoms, such as altered body composition, low energy levels, reduced muscle and bone strength, insulin resistance, and impaired heart function.

Macimorelin mimics the biological effects of ghrelin, a GH-stimulating hormone, thereby boosting GH production in the body. A weak rise in blood GH levels after macimorelin administration confirms growth hormone deficiency.

Notably, blood ghrelin levels are often reduced in ALS patients, and stimulation of GH production was shown to improve survival and motor function in ALS mouse models. These beneficial effects are likely associated with ghrelin’s previously shown neuroprotective and anti-inflammatory properties.

Given that ghrelin is rapidly cleared from the body — limiting its use as a medicine — macimorelin may be a good candidate to promote the same therapeutic benefits of ghrelin without its fast clearance issue.

Steyn and his team will assess the therapeutic potential of macimorelin on ALS progression and disease-specific features in cellular and animal models of ALS.

The University of Queensland researchers are seeking funding from dedicated organizations for some parts of the preclinical development program and to conduct a subsequent investigator-initiated clinical trial to evaluate macimorelin’s safety, tolerability, and effectiveness in ALS patients.

Aeterna Zentaris, in collaboration with Novo Nordisk, is also developing macimorelin for the diagnosis of childhood-onset growth hormone deficiency, an area of significant unmet need.