Therapeutic for GUK1-mutant mitochondrial DNA depletion-deletions syndrome

This technology is a treatment for GUK1-associated mitochondrial DNA depletion-deletions syndrome (MDDS), targeting nucleotide metabolism for DNA repair and replication.

Unmet Need: Effective therapeutics for mitochondrial DNA depletion-deletion syndromes (MDDS)

Mitochondrial DNA depletion-deletion syndromes (MDDS) are a rare collection of diseases that are characterized by reductions or deletions of mitochondrial DNA, displaying a broad range of pathologies that affect a wide range of organ systems throughout the body depending on the specific mutation. There are currently no available FDA-approved therapeutics for these syndromes; current treatment options focus on palliative care but fail to address the underlying mitochondrial dysfunction and DNA instability caused by dysfunctional nucleotide metabolism.

The Technology: Therapeutic targeting nucleotide pool imbalance in GUK1-mutant MDDS

This technology identifies GUK1 mutations as a driver for a unique form of mitochondrial DNA depletion-deletion syndrome (MDDS) and proposes a therapeutic strategy of delivering deoxyguanosine, forodesine, or a combination of both to restore nucleotide metabolism. Correcting the nucleotide imbalance facilitates proper mitochondrial DNA repair and replication, addressing the root cause of mitochondrial dysfunction in GUK1-mutant MDDS. Additionally, this technology introduces novel mouse models of GUK1-mutant MDDS, essential for studying pathology and testing therapeutic interventions that cannot be evaluated in mouse models.

Applications:

• Treatment for MDDS and other diseases characterized by unbalanced nucleotide pools
• Treatment for peripheral neuropathy and leukoencephalopathy
• Mouse model for MDDS and other diseases characterized by unbalanced nucleotide pools
• Mouse model for GUK1-associated diseases

Advantages:

• Wide application for GUK1-mutant MDDS
• Clinically relevant animal models for more accurate study of MDDS
• Efficient treatment to target nucleotide pool imbalance

Lead Inventor:

Michio Hirano, M.D.

Patent Information:

Patent Pending(WO/2019/028108)

Related Publications:

• Hidalgo-Gutierrez A, Shintaku J, Ramon J, Barriocanal-Casado E, Pesini A, Saneto RP, Garrabou G, Milisenda JC, Matas-Garcia A, Gort L, Ugarteburu O, Gu Y, Koganti L, Wang T, Tadesse S, Meneri M, Sciacco M, Wang S, Tanji K, Horwitz MS, Dorschner MO, Mansukhani M, Comi GP, Ronchi D, Marti R, Ribes A, Tort F, Hirano M. “Guanylate kinase 1 deficiency: a novel and potentially treatable mitochondrial DNA depletion/deletions disease.” Ann Neurol. 2024 Sep 4

Tech Ventures Reference:

• IR CU23197

• Licensing Contact: Kristin Neuman