ALS

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive degeneration of motor neurons, leading to muscle wasting, paralysis, and ultimately, death. At Alfa Cytology, our team of seasoned biological experts has identified poly(ADP-ribose) polymerase (PARP) inhibitors as a promising approach for addressing ALS.

PARP as a Therapeutic Target for ALS

Despite decades of research, effective treatments for ALS remain elusive, making the need for novel therapeutic strategies paramount. PARP enzymes play a crucial role in DNA repair, gene expression, and cell death pathways. Overactivation of PARP-1, the most abundant and well-studied PARP isoform, has been implicated in the pathogenesis of various neurodegenerative disorders, including ALS. In ALS, excessive PARP-1 activation can trigger a form of cell death known as "parthanatos," which involves depletion of cellular NAD+ and ATP, leading to mitochondrial dysfunction and the release of apoptosis-inducing factor (AIF). This cascade of events ultimately results in the death of motor neurons, a hallmark of ALS.

Fig. 1 Mechanism of PARP-1 overactivation in amyotrophic lateral sclerosis. (Arruri V. K., et al. 2021)

PARP Inhibitor Development for ALS

PARP inhibitors can block the hyperactivation of PARP-1, preventing parthanatos and potentially slowing or halting the progression of ALS.

Preclinical studies in ALS animal models have shown that PARP inhibitors can provide neuroprotective effects, preserve neuromuscular function, and extend lifespan.
Inhibition of PARP by genetic and pharmacological approaches attenuated hnRANP1 and TDP-43 neuronal death in an in vitro drosophila model. These results emphasize the importance of PARP-1 inhibitors in the treatment of ALS.

Our Services

Through innovative research and advanced technology, Alfa Cytology delves into the mechanisms of PARP action and has the ability to help clients develop novel PARP inhibitors, as well as optimize the effectiveness of PARP inhibitors and identify their biomarkers, to accelerate the development of new ovarian cancer therapies. Through these strategic partnerships, we leverage our expertise in PARP biology, medicinal chemistry, and preclinical drug development to support our clients in accelerating their ALS drug discovery.

Small Molecule Inhibitors Development for ALS

Peptide Inhibitor Development for ALS

Our ALS Modeling Services

We understand the critical role animal models play in advancing ALS research. We offer state-of-the-art animal model development services tailored specifically for ALS studies, including pharmacokinetics studies and drug safety evaluation.

Model Type	Description	Insights
Transgenic Mice	Mice overexpressing mutant or wild-type human ALS genes (e.g., SOD1, TDP-43, FUS	Provide insights into mechanisms of protein aggregation and deposition. Greatly overexpress mutant proteins compared to endogenous levels.
Knock-in Mice	Mice expressing mutant ALS genes at physiological levels from gene targeting	Develop more slowly progressing phenotypes. Better reflect early-stage disease processes.
Chemically-Induced (ENU) Mutant Mice	Mice with ALS-relevant genetic changes induced by chemical mutagenesis	Express mutant ALS genes at physiological levels. Illustrate early-stage disease mechanisms.

Alfa Cytology is committed to advancing the field of ALS research and driving the development of novel, mechanism-based therapies. To achieve this goal, we actively engage in collaborative efforts with leading academic institutions and pharmaceutical companies. For more information about our PARP inhibitor development program for amyotrophic lateral sclerosis or to discuss potential collaborations, please don't hesitate to contact us.

Reference

Arruri V. K., Gundu C., and et al. PARP overactivation in neurological disorders. Mol Biol Rep. 2021, 48(3): 2833-2841.

For research use only. Not intended for any clinical use.