This technology presents engineered peptide inhibitors designed to selectively block lactate dehydrogenase A (LDHA) activity, offering a novel therapeutic approach for diseases characterized by elevated LDHA, such as cancer and metabolic disorders.
Background: Lactate dehydrogenase A (LDHA) is an enzyme that plays a key role in cellular metabolism by converting pyruvate to lactate. In many pathological conditions, particularly cancer, LDHA is overactive, leading to an altered metabolic state known as the Warburg effect, which supports tumor growth and survival. Current treatments targeting metabolic enzymes often lack specificity or efficacy, prompting the need for novel inhibitors that can selectively suppress LDHA activity. This technology addresses this unmet need by developing peptide-based inhibitors to effectively disrupt LDHA function.
Technology Overview: This technology involves the creation of engineered peptides specifically designed to inhibit LDHA activity. These peptides are derived from a core amino acid sequence and are optimized through selected substitutions, including both natural and non-natural amino acids, to enhance their binding affinity and inhibitory potency against LDHA. By targeting the active site of LDHA, these peptides reduce the enzyme’s ability to convert pyruvate into lactate, thereby interfering with the altered metabolic pathways leveraged by cancer cells and other diseases characterized by increased glycolysis. The invention includes various peptide variants, each fine-tuned for stronger inhibition and stability within biological systems. Experimental data demonstrate the effective suppression of LDHA activity both in vitro—using cultured cancer cell lines—and in vivo within tumor tissues, supporting the therapeutic potential of the technology. Moreover, this approach allows for the development of pharmaceutical compositions that can be administered through multiple delivery methods, enabling flexible treatment regimens. The design of these peptides and the comprehensive structural analyses ensure high specificity and minimize off-target effects, making the technology valuable for addressing diseases associated with LDHA overexpression.
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Advantages: • Selective inhibition of LDHA, reducing off-target effects common with small molecule inhibitors. • Engineered peptide variants provide enhanced binding affinity and stability. • Demonstrated efficacy both in vitro and in vivo against cancer cells and tumor tissues. • Potential for versatile formulation options, allowing for different administration routes. • Novel therapeutic approach addressing metabolic pathways critical to cancer progression and other diseases. • Capability to target diseases with elevated glycolytic activity beyond cancer, such as metabolic disorders.
Applications: • Treatment of various cancers characterized by high LDHA activity, aiming to inhibit tumor growth and survival. • Therapies for metabolic diseases involving abnormal LDHA function, including diabetes-related complications. • Potential treatment option for rare genetic conditions such as Birt-Hogg-Dubé syndrome linked to metabolic dysregulation. • Use in pharmaceutical compositions designed for targeted delivery of peptide inhibitors. • Research tool for studying LDHA function and metabolic pathways in pathological settings.
Intellectual Property Summary: Issued patent - 11,725,026 on 8/15/2023
Stage of Development: TRL 3. Experimental proof of concept, with engineered peptide inhibitors demonstrating selective LDHA inhibition and therapeutic activity in both in vitro cancer cell models and in vivo tumor studies.
Licensing Status: This technology is available for licensing.