Abstract: Biomarkers are not as commonly used in ALS drug development as in the drug development process for oncology. Biomarkers are important component of the ALS drug development pathway to demonstrate drug effect and target engagement. In a recent Phase 2A double-blind, randomized, placebo controlled clinical trial with GM604 (AKA MNTF, GM6), where ALS patients were treated with six doses of GM604 for two weeks and then continued to be evaluated for disease progression until 10 weeks after cessation of GM604 treatment, it was demonstrated that GM604 can modulate expression of ALS disease related genes, through pathways that bring about homeostasis of pertinent ALS biomarkers. The statistical significance in biomarker changes also correlate with treatment effects in clinical observations.

Abstract: One aspect of this study was to provide a bioinformatic analysis to assess whether the MNTF-derived peptide known as GM6 alters the expression of genes associated with Alzheimer's disease. Gene expression analyses are performed using several gene expression profiling datasets generated by DNA microarray or RNA-seq technology. Our results show Alzheimer's disease-associated genes exhibit unique responses to GM6 treatment, impacting signaling pathways linked to core processes that underlie Alzheimer's disease onset and progression. The expression of one or more genes or gene variants of particular interest described herein. We show that ALS patients treated with GM6 exhibit significantly decreased abundance of plasma tau post-treatment (FIG. 1D). We also show that GM6 repressed MAPT mRNA in SH-5YSY cells (FIG. 2).

Abstract: Biomarkers are not as commonly used in ALS drug development as in the drug development process for oncology. Biomarkers are important component of the ALS drug development pathway to demonstrate drug effect and target engagement. In a recent Phase 2A double-blind, randomized, placebo controlled clinical trial with GM604 (AKA MNTF, GM6), where ALS patients were treated with six doses of GM604 for two weeks and then continued to be evaluated for disease progression until 10 weeks after cessation of GM604 treatment, it was demonstrated that GM604 can modulate expression of ALS disease related genes, through pathways that bring about homeostasis of pertinent ALS biomarkers. The statistical significance in biomarker changes also correlate with treatment effects in clinical observations.

Abstract: The present invention provides methods for inducing differentiation of an embryonic stem cell into a motor neuron using a motoneuronotrophic factor (MNTF) or its peptide analogs. The present invention further provides a method for isolating a population of stem cell derived motor neurons and a population of cells comprising the differentiated neural cells. Additionally, the present invention is directed to a method of enhancing the survival of the differentiated neural cells in long term cell cultures. Finally, the present invention provides compositions containing MNTF or its peptide analogs for therapeutic use in conjunction with stem cells.

Abstract: The present invention relates to novel Motoneuronotrophic Factors (MNTF) peptides and analogs thereof, including compositions capable of promoting the growth and viability of neurons. MNTF peptides between two and six amino acids in length are provided, as well as analogs of these MNTF peptides that are modified by covalent attachment to another moiety. Other embodiments are described herein.

Abstract: The present disclosure relates to methods for treating neuronal disorders using a motoneuronotrophic factor (MNTF) or its peptide analogs. The present disclosure further relates to methods for treating a spinal cord injury, a neurodegenerative disease, a stroke or cerebral ischemia, Huntington's Disease, Parkinson's Disease, Multiple Sclerosis, amyotrophic lateral sclerosis (ALS), Alzheimer's Disease, and diabetic neuropathy in a subject by administration of motoneuronotrophic factor (MNTF) or its peptide analogs.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating viability and growth in neuronal cells, and to methods of modulating neuronal cell viablility and growth employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to novel peptide analogues of motoneuronotrophic factor 1 containing either a “WMLSAFS” or “FSRYAR domain,” which is sufficient for neurotrophic and neurotropic function.

Abstract: The present invention provides methods for inducing differentiation of an embryonic stem cell into a motor neuron using a motoneuronotrophic factor (MNTF) or its peptide analogues. The present invention further provides a method for isolating a population of stem cell derived motor neurons and a population of cells comprising the differentiated neural cells. Additionally, the present invention is directed to a method of enhancing the survival of the differentiated neural cells in long term cell cultures. Finally, the present invention provides compositions containing MNTF or its peptide analogs for therapeutic use in conjunction with stem cells.

Abstract: The present invention is directed to a novel purified polypeptide consisting of an amino acid sequence as set forth in SEQ ID NO: 4, one of the member of the Motoneuronotrophic Factor family which has shown to have diagnostic and therapeutic applications in mammals.

Abstract: The present disclosure relates to methods for treating neuronal disorders using a motoneuronotrophic factor (MNTF) or its peptide analogs. The present disclosure further relates to methods for treating a spinal cord injury, a neurodegenerative disease, a stroke or cerebral ischemia, Huntington's Disease, Parkinson's Disease, Multiple Sclerosis, amyotrophic lateral sclerosis (ALS), Alzheimer's Disease, and diabetic neuropathy in a subject by administration of motoneuronotrophic factor (MNTF) or its peptide analogs.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating viability and growth in neuronal cells, and to methods of modulating neuronal cell viability and growth employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to novel peptide analogues of motoneuronotrophic factor 1 containing either a “WMLSAFS” or “FSRYAR domain,” which is sufficient for neurotrophic or neurotropic function.

Abstract: The present invention is directed to novel peptides and compositions capable of modulating viability and growth in neuronal cells, and to methods of modulating neuronal cell viability and growth employing the novel peptides and compositions of the invention. In one aspect, the invention is directed to novel peptide analogues of motoneuronotrophic factor 1 containing either a “WMLSAFS” or “FSRYAR domain,” which is sufficient for neurotrophic or neurotropic function.

Abstract: The invention is directed to a method of administering motoneuronotrophic factors for promoting the survival, growth, proliferation, or maintenance of mammalian neurons. The method is useful for promoting the survival, growth, proliferation, regeneration, or maintenance of mammalian neurons, promoting axonal regeneration, for inhibiting the effects of hereditary motoneuron disease, for minimizing or inhibiting the effects of scar tissue formation, and for accelerating wound healing while concomitantly minimizing or inhibiting the effects of scar tissue and keloid formation.

Abstract: An isolated polynucleotide encoding motoneuronotrophic factor F6.