South Korea-based Genuv Inc. announced the publication of a preclinical study showing the potential of Mekinist, approved by the FDA for melanoma, in Alzheimer’s disease.
Genuv Laboraties, Courtesy of Genuv Inc.
South Korea-based Genuv Inc. announced the publication of a preclinical study showing that Mekinist (trametinib), developed by Novartis and approved by the FDA for melanoma, has a neuroprotective effect in Alzheimer’s disease.
The data, published in Nature Molecular Psychiatry, revealed that in mice treated with Mekinist, brain cells became more adept at getting rid of clumps of protein, greatly reducing amyloid beta plaques.
Along with preventing the large-scale death of neurons in mice, the researchers reported that the drug was also able to repair damaged nerve structures and impaired synaptic function. In turn, mice given Mekinist orally recovered cognitive functions that had been lost due to Alzheimer’s. They demonstrated better results in maze tests and were able to recognize new objects.
“We are excited to share these extremely encouraging preclinical results,” Sungho Han, Ph.D., founder and CEO of Genuv said in a statement. “We believe we have demonstrated early proof of a new approach to neurodegenerative disease, focused on neuroprotection and neurogenesis.”
Han added that Genuv plans to continue its pre-clinical exploration of MEK 1/2 inhibitors.
Developed by pharma powerhouse GlaxoSmithKline, Mekinist was first granted FDA approval in June 2013 for advanced melanoma. The drug works by targeting and deactivating the MEK 1 and 2 proteins, blocking a signaling cascade that culminates in cell multiplication.
By suppressing cellular proliferation, Mekinist has established a respectable foothold in the oncology space. In the years following its melanoma greenlight, the drug earned even more FDA nods, including for the treatment of non-small cell lung cancer and thyroid cancer. In June, Mekinist, in combination with Novartis’ Tafinlar (dabrafenib), was granted accelerated approval for patients with unresectable and metastatic solid tumors.
But Genuv is looking to take the cancer drug in an entirely new direction. Using its proprietary drug screening platform ATRIVIEW, the clinical-stage company looks for new and existing therapies that are both neuroprotective and neurogenic- those that act via previously unknown pathways to preserve and promote homeostasis in the brain and induce adult neural stem cells to differentiate into neurons.
“Our hypothesis was that in order to develop treatments for neurodegenerative diseases, we need healthy neurons to restore the impaired cognitive functions of Alzheimer’s patients,” Han told BioSpace. “We, therefore, looked for substances that could induce the differentiation of endogenous neural stem cells in the brain to replenish damaged neurons and restore neural network function.”
Mekinist, which Genuv has labeled SNR1611, is the lead candidate out of ATRIVIEW and has demonstrated the strongest potential out of a long list of other FDA-approved compounds.
Mekinist has already been granted an IND for amyotrophic lateral sclerosis (ALS) and is now undergoing Phase I/IIa studies for this indication. Genuv is also developing another MEK1/2 inhibitor, named GNUV101, for an unnamed neurodegenerative disease.
In recent months, Alzheimer’s research has been rocked by a slew of data fabrication controversies. In July, a Science investigation found that Western blot images supporting a central theory - that the amyloid oligomer Aβ*56 is tied to memory loss in Alzheimer’s - could have potentially been manipulated. Cassava Sciences, another prominent player in the Alzheimer’s space, has also been accused of doctoring data to support its drug simufilam.
While these controversies have shaken confidence in the field, they have also renewed interest in alternative ways of treating Alzheimer’s. Genuv appears ready to make the most of this opportunity with its neuroprotection/neurogenesis approach.
“Drug development based on the beta-amyloid hypothesis has a long history of clinical failures, particularly for Alzheimer’s disease,” Han told BioSpace. “Drug repurposing can speed development and lower costs because these treatments have known safety profiles and pharmacokinetics.”
